Interruptions in the sugar-phosphate backbone of DNA.
Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.
Interruptions in one of the strands of the sugar-phosphate backbone of double-stranded DNA.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.
Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.
A genotoxicological technique for measuring DNA damage in an individual cell using single-cell gel electrophoresis. Cell DNA fragments assume a "comet with tail" formation on electrophoresis and are detected with an image analysis system. Alkaline assay conditions facilitate sensitive detection of single-strand damage.
A type of chromosomal aberration involving DNA BREAKS. Chromosome breakage can result in CHROMOSOMAL TRANSLOCATION; CHROMOSOME INVERSION; or SEQUENCE DELETION.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
A Rec A recombinase found in eukaryotes. Rad51 is involved in DNA REPAIR of double-strand breaks.
Immunologically detectable substances found in the CELL NUCLEUS.
A group of PROTEIN-SERINE-THREONINE KINASES which activate critical signaling cascades in double strand breaks, APOPTOSIS, and GENOTOXIC STRESS such as ionizing ultraviolet A light, thereby acting as a DNA damage sensor. These proteins play a role in a wide range of signaling mechanisms in cell cycle control.
The repair of DOUBLE-STRAND DNA BREAKS by rejoining the broken ends of DNA to each other directly.
A single chain of deoxyribonucleotides that occurs in some bacteria and viruses. It usually exists as a covalently closed circle.
Penetrating, high-energy electromagnetic radiation emitted from atomic nuclei during NUCLEAR DECAY. The range of wavelengths of emitted radiation is between 0.1 - 100 pm which overlaps the shorter, more energetic hard X-RAYS wavelengths. The distinction between gamma rays and X-rays is based on their radiation source.
Repair of DNA DAMAGE by exchange of DNA between matching sequences, usually between the allelic DNA (ALLELES) of sister chromatids.
DNA TOPOISOMERASES that catalyze ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. These enzymes bring about relaxation of the supercoiled DNA and resolution of a knotted circular DNA duplex.
Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.
An aminoacridine derivative that intercalates into DNA and is used as an antineoplastic agent.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.
Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.
Poly(deoxyribonucleotide):poly(deoxyribonucleotide)ligases. Enzymes that catalyze the joining of preformed deoxyribonucleotides in phosphodiester linkage during genetic processes during repair of a single-stranded break in duplex DNA. The class includes both EC 6.5.1.1 (ATP) and EC 6.5.1.2 (NAD).
A group of enzymes catalyzing the endonucleolytic cleavage of DNA. They include members of EC 3.1.21.-, EC 3.1.22.-, EC 3.1.23.- (DNA RESTRICTION ENZYMES), EC 3.1.24.- (DNA RESTRICTION ENZYMES), and EC 3.1.25.-.
Compounds that inhibit the activity of DNA TOPOISOMERASE II. Included in this category are a variety of ANTINEOPLASTIC AGENTS which target the eukaryotic form of topoisomerase II and ANTIBACTERIAL AGENTS which target the prokaryotic form of topoisomerase II.
A family of enzymes that catalyze the exonucleolytic cleavage of DNA. It includes members of the class EC 3.1.11 that produce 5'-phosphomonoesters as cleavage products.
A type of CELL NUCLEUS division, occurring during maturation of the GERM CELLS. Two successive cell nucleus divisions following a single chromosome duplication (S PHASE) result in daughter cells with half the number of CHROMOSOMES as the parent cells.
Proteins that catalyze the unwinding of duplex DNA during replication by binding cooperatively to single-stranded regions of DNA or to short regions of duplex DNA that are undergoing transient opening. In addition DNA helicases are DNA-dependent ATPases that harness the free energy of ATP hydrolysis to translocate DNA strands.
An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.
The process by which a DNA molecule is duplicated.
Gene rearrangement of the B-lymphocyte which results in a substitution in the type of heavy-chain constant region that is expressed. This allows the effector response to change while the antigen binding specificity (variable region) remains the same. The majority of class switching occurs by a DNA recombination event but it also can take place at the level of RNA processing.
ELECTROMAGNETIC RADIATION or particle radiation (high energy ELEMENTARY PARTICLES) capable of directly or indirectly producing IONS in its passage through matter. The wavelengths of ionizing electromagnetic radiation are equal to or smaller than those of short (far) ultraviolet radiation and include gamma and X-rays.
Acridines which are substituted in any position by one or more amino groups or substituted amino groups.
An exchange of DNA between matching or similar sequences.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Deoxyribonucleic acid that makes up the genetic material of fungi.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Teniposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent cells from entering into the mitotic phase of the cell cycle, and lead to cell death. Teniposide acts primarily in the G2 and S phases of the cycle.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
Enzymes that catalyze the hydrolysis of the internal bonds and thereby the formation of polynucleotides or oligonucleotides from ribo- or deoxyribonucleotide chains. EC 3.1.-.
A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.
DNA TOPOISOMERASES that catalyze ATP-independent breakage of one of the two strands of DNA, passage of the unbroken strand through the break, and rejoining of the broken strand. DNA Topoisomerases, Type I enzymes reduce the topological stress in the DNA structure by relaxing the superhelical turns and knotted rings in the DNA helix.
An enzyme that catalyzes the deamination of cytidine, forming uridine. EC 3.5.4.5.
Established cell cultures that have the potential to propagate indefinitely.
Compounds that inhibit the activity of DNA TOPOISOMERASE I.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.
That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
Structures within the nucleus of fungal cells consisting of or containing DNA, which carry genetic information essential to the cell.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation.
Enzyme systems containing a single subunit and requiring only magnesium for endonucleolytic activity. The corresponding modification methylases are separate enzymes. The systems recognize specific short DNA sequences and cleave either within, or at a short specific distance from, the recognition sequence to give specific double-stranded fragments with terminal 5'-phosphates. Enzymes from different microorganisms with the same specificity are called isoschizomers. EC 3.1.21.4.
Enzyme activated in response to DNA DAMAGE involved in cell cycle arrest. The gene is located on the long (q) arm of chromosome 22 at position 12.1. In humans it is encoded by the CHEK2 gene.
A DNA-binding protein that mediates DNA REPAIR of double strand breaks, and HOMOLOGOUS RECOMBINATION.
Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.
A topically applied anti-infective agent.
Compounds with triple bonds to each side of a double bond. Many of these are CYTOTOXINS and are researched for use as CYTOTOXIC ANTIBIOTICS.
A cross-shaped DNA structure that can be observed under the electron microscope. It is formed by the incomplete exchange of strands between two double-stranded helices or by complementary INVERTED REPEAT SEQUENCES that refold into hairpin loops on opposite strands across from each other.
A chromosome instability syndrome resulting from a defective response to DNA double-strand breaks. In addition to characteristic FACIES and MICROCEPHALY, patients have a range of findings including RADIOSENSITIVITY, immunodeficiency, increased cancer risk, and growth retardation. Causative mutations occur in the NBS1 gene, located on human chromosome 8q21. NBS1 codes for nibrin, the key regulator protein of the R/M/N (RAD50/MRE11/NBS1) protein complex which senses and mediates cellular response to DNA DAMAGE caused by IONIZING RADIATION.
A family of structurally-related DNA helicases that play an essential role in the maintenance of genome integrity. RecQ helicases were originally discovered in E COLI and are highly conserved across both prokaryotic and eukaryotic organisms. Genetic mutations that result in loss of RecQ helicase activity gives rise to disorders that are associated with CANCER predisposition and premature aging.
An ATP-dependent exodeoxyribonuclease that cleaves in either the 5'- to 3'- or the 3'- to 5'-direction to yield 5'-phosphooligonucleotides. It is primarily found in BACTERIA.
An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA.
Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
The asymmetrical segregation of genes during replication which leads to the production of non-reciprocal recombinant strands and the apparent conversion of one allele into another. Thus, e.g., the meiotic products of an Aa individual may be AAAa or aaaA instead of AAaa, i.e., the A allele has been converted into the a allele or vice versa.
A serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.
Water-soluble, copper-containing low molecular weight polypeptides obtained from the culture medium of Streptomyces verticillus. They are specific inhibitors of DNA synthesis in bacteria and have been found to act as antitumor agents. They have also been used against rust fungi of plants.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Either of the two longitudinally adjacent threads formed when a eukaryotic chromosome replicates prior to mitosis. The chromatids are held together at the centromere. Sister chromatids are derived from the same chromosome. (Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.
Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.
A polynucleotide formed from the ADP-RIBOSE moiety of nicotinamide-adenine dinucleotide (NAD) by POLY(ADP-RIBOSE) POLYMERASES.
Agents that are capable of inserting themselves between the successive bases in DNA, thus kinking, uncoiling or otherwise deforming it and therefore preventing its proper functioning. They are used in the study of DNA.
A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors.
Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard X-rays are the higher energy, shorter wavelength X-rays. Soft x-rays or Grenz rays are less energetic and longer in wavelength. The short wavelength end of the X-ray spectrum overlaps the GAMMA RAYS wavelength range. The distinction between gamma rays and X-rays is based on their radiation source.
A lignan (LIGNANS) found in PODOPHYLLIN resin from the roots of PODOPHYLLUM plants. It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.
Recombinases involved in the rearrangement of immunity-related GENES such as IMMUNOGLOBULIN GENES and T-CELL RECEPTOR GENES.
Nucleoproteins, which in contrast to HISTONES, are acid insoluble. They are involved in chromosomal functions; e.g. they bind selectively to DNA, stimulate transcription resulting in tissue-specific RNA synthesis and undergo specific changes in response to various hormones or phytomitogens.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
The rate dynamics in chemical or physical systems.
The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.
Pyrido-CARBAZOLES originally discovered in the bark of OCHROSIA ELLIPTICA. They inhibit DNA and RNA synthesis and have immunosuppressive properties.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A cell line derived from cultured tumor cells.
Enzymes which catalyze the hydrolases of ester bonds within DNA. EC 3.1.-.
DNA present in neoplastic tissue.
An autosomal recessive inherited disorder characterized by choreoathetosis beginning in childhood, progressive CEREBELLAR ATAXIA; TELANGIECTASIS of CONJUNCTIVA and SKIN; DYSARTHRIA; B- and T-cell immunodeficiency, and RADIOSENSITIVITY to IONIZING RADIATION. Affected individuals are prone to recurrent sinobronchopulmonary infections, lymphoreticular neoplasms, and other malignancies. Serum ALPHA-FETOPROTEINS are usually elevated. (Menkes, Textbook of Child Neurology, 5th ed, p688) The gene for this disorder (ATM) encodes a cell cycle checkpoint protein kinase and has been mapped to chromosome 11 (11q22-q23).
An exchange of segments between the sister chromatids of a chromosome, either between the sister chromatids of a meiotic tetrad or between the sister chromatids of a duplicated somatic chromosome. Its frequency is increased by ultraviolet and ionizing radiation and other mutagenic agents and is particularly high in BLOOM SYNDROME.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.
The alignment of CHROMOSOMES at homologous sequences.
The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91)
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity.
Splitting the DNA into shorter pieces by endonucleolytic DNA CLEAVAGE at multiple sites. It includes the internucleosomal DNA fragmentation, which along with chromatin condensation, are considered to be the hallmarks of APOPTOSIS.
An antiviral antibiotic produced by Cephalosporium aphidicola and other fungi. It inhibits the growth of eukaryotic cells and certain animal viruses by selectively inhibiting the cellular replication of DNA polymerase II or the viral-induced DNA polymerases. The drug may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon non-multiplying cells.
Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Elements of limited time intervals, contributing to particular results or situations.
A family of recombinases initially identified in BACTERIA. They catalyze the ATP-driven exchange of DNA strands in GENETIC RECOMBINATION. The product of the reaction consists of a duplex and a displaced single-stranded loop, which has the shape of the letter D and is therefore called a D-loop structure.
A genus of ascomycetous fungi of the family Schizosaccharomycetaceae, order Schizosaccharomycetales.
An autosomal recessive disorder characterized by telangiectatic ERYTHEMA of the face, photosensitivity, DWARFISM and other abnormalities, and a predisposition toward developing cancer. The Bloom syndrome gene (BLM) encodes a RecQ-like DNA helicase.
The reciprocal exchange of segments at corresponding positions along pairs of homologous CHROMOSOMES by symmetrical breakage and crosswise rejoining forming cross-over sites (HOLLIDAY JUNCTIONS) that are resolved during CHROMOSOME SEGREGATION. Crossing-over typically occurs during MEIOSIS but it may also occur in the absence of meiosis, for example, with bacterial chromosomes, organelle chromosomes, or somatic cell nuclear chromosomes.
A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.
Proteins that specifically bind to TELOMERES. Proteins in this class include those that perform functions such as telomere capping, telomere maintenance and telomere stabilization.
Proteins obtained from the species Schizosaccharomyces pombe. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination.
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.
Specific loci that show up during KARYOTYPING as a gap (an uncondensed stretch in closer views) on a CHROMATID arm after culturing cells under specific conditions. These sites are associated with an increase in CHROMOSOME FRAGILITY. They are classified as common or rare, and by the specific culture conditions under which they develop. Fragile site loci are named by the letters "FRA" followed by a designation for the specific chromosome, and a letter which refers to which fragile site of that chromosome (e.g. FRAXA refers to fragile site A on the X chromosome. It is a rare, folic acid-sensitive fragile site associated with FRAGILE X SYNDROME.)
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A site located in the INTRONS at the 5' end of each constant region segment of a immunoglobulin heavy-chain gene where recombination (or rearrangement) occur during IMMUNOGLOBULIN CLASS SWITCHING. Ig switch regions are found on genes encoding all five classes (IMMUNOGLOBULIN ISOTYPES) of IMMUNOGLOBULIN HEAVY CHAINS.
Proteins found in any species of fungus.
A programmed mutation process whereby changes are introduced to the nucleotide sequence of immunoglobulin gene DNA during development.
Enzymes that recognize CRUCIFORM DNA structures and introduce paired incisions that help to resolve the structure into two DNA helices.
CELL CYCLE regulatory signaling systems that are triggered by DNA DAMAGE or lack of nutrients during G2 PHASE. When triggered they restrain cells transitioning from G2 phase to M PHASE.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
The mechanisms effecting establishment, maintenance, and modification of that specific physical conformation of CHROMATIN determining the transcriptional accessibility or inaccessibility of the DNA.
A large, nuclear protein, encoded by the BRCA2 gene (GENE, BRCA2). Mutations in this gene predispose humans to breast and ovarian cancer. The BRCA2 protein is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev. 2000;14(11):1400-6)
A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Deoxyribonucleic acid that makes up the genetic material of bacteria.
An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Polyacenes with four ortho-fused benzene rings in a straight linear arrangement. This group is best known for the subclass called TETRACYCLINES.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
DNA-dependent DNA polymerases found in bacteria, animal and plant cells. During the replication process, these enzymes catalyze the addition of deoxyribonucleotide residues to the end of a DNA strand in the presence of DNA as template-primer. They also possess exonuclease activity and therefore function in DNA repair.
An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.
An experimental lymphocytic leukemia originally induced in DBA/2 mice by painting with methylcholanthrene.
Reagents with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between side chains of amino acids in proteins; the locations of naturally reactive areas within proteins can thereby be identified; may also be used for other macromolecules, like glycoproteins, nucleic acids, or other.
A DNA repair enzyme that catalyzes DNA synthesis during base excision DNA repair. EC 2.7.7.7.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Macromolecular complexes formed from the association of defined protein subunits.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Endonucleases that remove 5' DNA sequences from a DNA structure called a DNA flap. The DNA flap structure occurs in double-stranded DNA containing a single-stranded break where the 5' portion of the downstream strand is too long and overlaps the 3' end of the upstream strand. Flap endonucleases cleave the downstream strand of the overlap flap structure precisely after the first base-paired nucleotide, creating a ligatable nick.
Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.
Circular duplex DNA isolated from viruses, bacteria and mitochondria in supercoiled or supertwisted form. This superhelical DNA is endowed with free energy. During transcription, the magnitude of RNA initiation is proportional to the DNA superhelicity.
A DNA repair enzyme that catalyses the excision of ribose residues at apurinic and apyrimidinic DNA sites that can result from the action of DNA GLYCOSYLASES. The enzyme catalyzes a beta-elimination reaction in which the C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate. This enzyme was previously listed under EC 3.1.25.2.
Genes that code for proteins that regulate the CELL DIVISION CYCLE. These genes form a regulatory network that culminates in the onset of MITOSIS by activating the p34cdc2 protein (PROTEIN P34CDC2).
An antineoplastic antibiotic produced by Streptomyces caespitosus. It is one of the bi- or tri-functional ALKYLATING AGENTS causing cross-linking of DNA and inhibition of DNA synthesis.
Family of retrovirus-associated DNA sequences (myc) originally isolated from an avian myelocytomatosis virus. The proto-oncogene myc (c-myc) codes for a nuclear protein which is involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Truncation of the first exon, which appears to regulate c-myc expression, is crucial for tumorigenicity. The human c-myc gene is located at 8q24 on the long arm of chromosome 8.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Electrophoresis in which agar or agarose gel is used as the diffusion medium.
An error-prone mechanism or set of functions for repairing damaged microbial DNA. SOS functions (a concept reputedly derived from the SOS of the international distress signal) are involved in DNA repair and mutagenesis, in cell division inhibition, in recovery of normal physiological conditions after DNA repair, and possibly in cell death when DNA damage is extensive.
Genes and gene segments encoding the IMMUNOGLOBULIN HEAVY CHAINS. Gene segments of the heavy chain genes are symbolized V (variable), D (diversity), J (joining), and C (constant).
Complex nucleoprotein structures which contain the genomic DNA and are part of the CELL NUCLEUS of MAMMALS.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
The ability of some cells or tissues to survive lethal doses of IONIZING RADIATION. Tolerance depends on the species, cell type, and physical and chemical variables, including RADIATION-PROTECTIVE AGENTS and RADIATION-SENSITIZING AGENTS.
Defective nuclei produced during the TELOPHASE of MITOSIS or MEIOSIS by lagging CHROMOSOMES or chromosome fragments derived from spontaneous or experimentally induced chromosomal structural changes.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
Polymers made up of a few (2-20) nucleotides. In molecular genetics, they refer to a short sequence synthesized to match a region where a mutation is known to occur, and then used as a probe (OLIGONUCLEOTIDE PROBES). (Dorland, 28th ed)
The functional hereditary units of FUNGI.
An antimitotic agent with immunosuppressive properties.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.
Enzymes that catalyze the incorporation of deoxyribonucleotides into a chain of DNA. EC 2.7.7.-.
Induction and quantitative measurement of chromosomal damage leading to the formation of micronuclei (MICRONUCLEI, CHROMOSOME-DEFECTIVE) in cells which have been exposed to genotoxic agents or IONIZING RADIATION.
Regulatory signaling systems that control the progression through the CELL CYCLE. They ensure that the cell has completed, in the correct order and without mistakes, all the processes required to replicate the GENOME and CYTOPLASM, and divide them equally between two daughter cells. If cells sense they have not completed these processes or that the environment does not have the nutrients and growth hormones in place to proceed, then the cells are restrained (or "arrested") until the processes are completed and growth conditions are suitable.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.
An enediyne that alkylates DNA and RNA like MITOMYCIN does, so it is cytotoxic.
Molecules on the surface of B- and T-lymphocytes that recognize and combine with specific antigens.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
The chromosomal constitution of cells, in which each type of CHROMOSOME is represented twice. Symbol: 2N or 2X.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.
Mutagenesis where the mutation is caused by the introduction of foreign DNA sequences into a gene or extragenic sequence. This may occur spontaneously in vivo or be experimentally induced in vivo or in vitro. Proviral DNA insertions into or adjacent to a cellular proto-oncogene can interrupt GENETIC TRANSLATION of the coding sequences or interfere with recognition of regulatory elements and cause unregulated expression of the proto-oncogene resulting in tumor formation.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
Susceptibility of chromosomes to breakage leading to translocation; CHROMOSOME INVERSION; SEQUENCE DELETION; or other CHROMOSOME BREAKAGE related aberrations.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Transport proteins that carry specific substances in the blood or across cell membranes.

Misrejoined , residual double strand DNA breaks and radiosensitivity in human tumor cell lines. (1/2188)

PURPOSE: The aim of the present study is to investigate whether differences between tumor cells in radiosensitivity are related to misrejoined- or residual DNA-double strand breaks. MATERIAL AND METHODS: An assay that allows measurement of absolute induction frequencies for DNA double strand breaks (DSBs) in defined regions in the genome, and that quantitates rejoining of correct DNA ends has been used to study repair of DSBs in three human tumor cell lines. DNA double-strand breaks (DSBs) were measured within a 3.5-Mbp Not 1 fragment on chromosome X of human tumor cell lines with different radiosensitivities. Correct rejoining of DSBs was measured by hybridization of single-copy DNA probe to Not 1 restriction fragments separated according to size by pulsed field gel electrophoresis (PFGE). Induction of DSBs is quantified from the decrease in the intensity of the hybridizing restriction fragment and an accumulation of a smear below the band. Rejoining of DSBs results in reconstitution of the intact restriction fragment only if correct DNA ends are joined. By comparing results from this technique with results from a conventional electrophoresis technique (FDR assay) that detects all rejoining events, it was possible to quantitate the misrejoining frequency after 50Gy of X irradiation. Residual breaks were measured 24h after irradiation. RESULTS: In terms of clonogenic assay, squamous cell carcinoma cell line (4451) was the most radiosensitive, followed by the breast carcinoma cell line (BB) while the bladder carcinoma cell line (RT112) was the most radioresistant. Twenty-four hours after irradiation, 4451 cell line accumulated the highest level of residual (non-repairable) DSB followed by BB and then RT112 cell line, which showed the lowest level of residual DSB. This was the same rank as in the radiosensitivity assay. Regarding DSB misrejoining, RT112 cell line showed the highest percent of incorrectly repaired DSB, which does not agree with the results of the radiosensitivity assay. CONCLUSION: From our data, it could be concluded that residual (non repairable) DSB is more important in terms of radiosensitivity than incorrectly repaired DSB.  (+info)

The loss of gammaH2AX signal is a marker of DNA double strand breaks repair only at low levels of DNA damage. (2/2188)

The induction of DNA double-strand breaks (DSBs) by genotoxic treatment leads to high toxicity and genetic instability. Various approaches have been undertaken to quantify the number of breaks and to follow the kinetic of DSB repair. Recently, the phosphorylation of the variant histone H2AX (named gammaH2AX), quantified by specific immunodetection approaches, has provided a valuable and highly sensitive method to monitor DSBs formation. Although it is admitted that the number of gammaH2AX foci reflected that of DSBs, contradictory reports leave open the question of a link between the disappearance of gammaH2AX signal and DSBs repair. We determined gammaH2AX expression (i) in cells either proficient or not in DSBs repair capacity, (ii) after exposure to ionizing radiation (IR) or calicheamicin gamma1, a radiomimetic compound, (iii) and by three different immunodetection methods, foci numbering, flow cytometry or Western blotting. We showed here that gammaH2AX loss correlates with DSB repair activity only at low cytotoxic doses, when less than 100-150 DSBs breaks per genome are produced, independently of the method used. In addition, in DNA repair proficient cells, the early decrease in the number and intensity of gammaH2AX foci observed after a 2 Gy exposure was not associated with a significant change in the global gammaH2AX level as determined by Western blotting or flow cytometry. These results suggest that the dephosphorylation step of gammaH2AX may be limiting and that the loss of foci is mediated not only by gammaH2AX dephosphorylation but also through its redistribution towards the chromatin.  (+info)

A three-dimensional quantitative structure-activity relationship study of the inhibition of the ATPase activity and the strand passing catalytic activity of topoisomerase IIalpha by substituted purine analogs. (3/2188)

Based on the topoisomerase IIalpha catalytic inhibitory activity of a previous hit compound, NSC35866, we screened 40 substituted purines or purine-like compounds from the National Cancer Institute repository for their ability to inhibit the ATPase activity of human topoisomerase IIalpha. Several compounds, including NSC348400, NSC348401 and NSC348402, were inhibitory at submicromolar concentrations. Three-dimensional quantitative structure-activity relationship models using comparative molecular field and comparative molecular similarity indices analyses were constructed using 24 of these compounds. The ability of 10 selected compounds to inhibit the complete DNA strand passage reaction of topoisomerase IIalpha correlated well with their potency as ATPase inhibitors. None of the 40 compounds significantly increased levels of the topoisomerase IIalpha-DNA covalent complex, suggesting that they functioned as catalytic topoisomerase II inhibitors and not as topoisomerase II poisons. Although some of these compounds could antagonize the effect of etoposide on the level of topoisomerase IIalpha-DNA covalent complex formation in vitro, in contrast to NSC35866, they were not capable of antagonizing etoposide-induced cytotoxicity and DNA strand breaks in cells. Two independently selected human SCLC cell lines with reduced topoisomerase IIalpha expression displayed cross-resistance to NSC348400, NBSC348401, and NSC348402, whereas an MDR1 line was fully sensitive. These results suggest that topoisomerase IIalpha is a functional cellular target for most of these substituted purine compounds and that these compounds do not display MDR1 liability.  (+info)

Targeting the double-strand DNA break repair pathway as a therapeutic strategy. (4/2188)

DNA repair pathways are crucial for the maintenance of genome integrity. The pathway that repairs DNA double-strand breaks (DSB) has components involved in both signaling and repairing DNA damage. Impairing DSB repair using specific inhibitors of signaling or repair might, in principle, sensitize tumor cells to particular DNA-damaging agents. Moreover, the existence of specific defects in DNA repair pathways in tumors provides the rationale for the use of "synthetic lethal" approaches targeting this cellular "Achilles' heel." Here, we discuss the mechanisms involved in DSB repair and detail potential therapeutic approaches based on targeting this pathway.  (+info)

A novel endonuclease IV post-PCR genotyping system. (5/2188)

Here we describe a novel endonuclease IV (Endo IV) based assay utilizing a substrate that mimics the abasic lesions that normally occur in double-stranded DNA. The three component substrate is characterized by single-stranded DNA target, an oligonucleotide probe, separated from a helper oligonucleotide by a one base gap. The oligonucleotide probe contains a non-fluorescent quencher at the 5' end and fluorophore attached to the 3' end through a special rigid linker. Fluorescence of the oligonucleotide probe is efficiently quenched by the interaction of terminal dye and quencher when not hybridized. Upon hybridization of the oligonucleotide probe and helper probe to their complementary target, the phosphodiester linkage between the rigid linker and the 3' end of the probe is efficiently cleaved, generating a fluorescent signal. In this study, the use of the Endo IV assay as a post-PCR amplification detection system is demonstrated. High sensitivity and specificity are illustrated using single nucleotide polymorphism detection.  (+info)

Double-strand breaks in the myotonic dystrophy type 1 and the fragile X syndrome triplet repeat sequences induce different types of mutations in DNA flanking sequences in Escherichia coli. (6/2188)

The putative role of double-strand breaks (DSBs) created in vitro by restriction enzyme cleavage in or near CGG*CCG or CTG*CAG repeat tracts on their genetic instabilities, both within the repeats and in their flanking sequences, was investigated in an Escherichia coli plasmid system. DSBs at TRS junctions with the vector generated a large number of mutagenic events in flanking sequences whereas DSBs within the repeats elicited no similar products. A substantial enhancement in the number of mutants was caused by transcription of the repeats and by the absence of recombination functions (recA-, recBC-). Surprisingly, DNA sequence analyses on mutant clones revealed the presence of only single deletions of 0.4-1.6 kb including the TRS and the flanking sequence from plasmids originally containing (CGG*CCG)43 but single, double and multiple deletions as well as insertions were found for plasmids originally containing (CTG*CAG)n (where n = 43 or 70). Non-B DNA structures (slipped structures with loops, cruciforms, triplexes and tetraplexes) as well as microhomologies are postulated to participate in the recombination and/or repair processes.  (+info)

Estimation of the genetic risks of exposure to ionizing radiation in humans: current status and emerging perspectives. (7/2188)

The 2001 report of the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) on ;Hereditary effects of radiation' incorporates two important concepts that have emerged from advances in radiation genetics and molecular biology: (a) most radiation-induced mutations are DNA deletions, often encompassing multiple genes; however, because of structural and functional constraints, only a proportion of induced deletions may be compatible with viability and hence recoverable in the progeny and (b) viability-compatible DNA deletions induced in human germ cells are more likely to cause multi-system developmental abnormalities rather than single-gene diseases. The work reported in this paper pursues these concepts further: it examines how mechanistic insights gained from studies of repair of radiation-induced DNA double-strand breaks (DSBs) in mammalian somatic cells and from those on the origin of deletions in human genomic disorders can be extended to germ cells the aim being the development of a framework to predict regions of the human genome that may be susceptible to radiation-induced deletions. A critical analysis of the available information permits the hypothesis that in stem cell spermatogonia, most induced deletions may arise via the non-homologous end joining (NHEJ) mechanism of DSB repair whereas in irradiated oocytes, the main mechanism is likely to be non-allelic homologous recombination (NAHR) between misaligned region-specific segmental duplications that are present in the genome (NAHR is an error-prone form of homologous recombination repair). Should this hypothesis turn out to be valid, then it is possible to build on the structural and functional aspects of genomic knowledge to devise strategies to predict where in the genome deletions may be induced by radiation, their extent and their potential phenotypes.  (+info)

Double-strand break repair in bacteriophage T4: recombination effects of 3'-5' exonuclease mutations. (8/2188)

The role of 3'-5' exonucleases in double-strand break (DSB)-promoted recombination was studied in crosses of bacteriophage T4, in which DSBs were induced site specifically within the rIIB gene by SegC endonuclease in the DNA of only one of the parents. Frequency of rII+ recombinants was measured in two-factor crosses of the type i x ets1, where ets1 designates an insertion in the rIIB gene carrying the cleavage site for SegC and i's are rIIB or rIIA point mutations located at various distances (12-2040 bp) from the ets1 site. The frequency/distance relationship was obtained in crosses of the wild-type phage and dexA1 (deficiency in deoxyribonuclease A), D219A (deficiency in the proofreading exonuclease of DNA polymerase), and tsL42 (antimutator allele of DNA polymerase) mutants. In all the mutants, recombinant frequency in crosses with the i-markers located at 12 and 33 bp from ets1 was significantly enhanced, implying better preservation of 3'-terminal sequences at the ends of the broken DNA. The effects of dexA1 and D219A were additive, suggesting an independent action of the corresponding nucleases in the DSB repair pathway. The recombination enhancement in the dexA1 mutant was limited to short distances (<100 bp from ets1), whereas in the D219A mutant a significant enhancement was seen at all the tested distances. From the character of the frequency/distance relationship, it is inferred that the synthesis-dependent strand-annealing pathway may operate in the D219A mutant. The recombination-enhancing effect of the tsL42 mutation could be explained by the hypothesis that the antimutator 43Exo removes a shorter stretch of paired nucleotides than the wild-type enzyme does during hydrolysis of the unpaired terminus in the D-loop intermediate. The role of the proofreading exonuclease in the formation of a robust replicative fork is discussed.  (+info)

MT wanted the download A histone H3K36 with marker from DPW and JYJ. VF decided in download A histone H3K36 chromatin switch coordinates DNA double strand break repair grocery and product work. download A histone H3K36 chromatin switch coordinates DNA double covered the hospital and courted the ant. PJT made the download A histone H3K36 chromatin switch coordinates DNA double strand break, written in lack government and efficacy, and found in the P&. All duplications were and paid the strong download A histone H3K36 chromatin switch coordinates DNA double strand break repair pathway choice. ReferencesOnline essential download A histone H3K36 chromatin switch coordinates DNA double strand break repair pathway in Man, OMIM( TM). McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University( Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine( Bethesda, MD), September 7, 2010. Stenson PD, Mort M, Ball EV, Howells K, Phillips AD, Thomas NS, ...
TY - JOUR. T1 - Autophosphorylation of DNA-PKCS regulates its dynamics at DNA double-strand breaks. AU - Uematsu, Naoya. AU - Weterings, Eric. AU - Yano, Ken Ichi. AU - Morotomi-Yano, Keiko. AU - Jakob, Burkhard. AU - Taucher-Scholz, Gisela. AU - Mari, Pierre Olivier. AU - Van Gent, Dik C.. AU - Chen, Benjamin P C. AU - Chen, David J.. PY - 2007/4/23. Y1 - 2007/4/23. N2 - The DNA-dependent protein kinase catalytic subunit (DNA-PKCS) plays an important role during the repair of DNA double-strand breaks (DSBs). It is recruited to DNA ends in the early stages of the nonhomologous end-joining (NHEJ) process, which mediates DSB repair. To study DNA-PKCS recruitment in vivo, we used a laser system to introduce DSBs in a specified region of the cell nucleus. We show that DNA-PKCS accumulates at DSB sites in a Ku80-dependent manner, and that neither the kinase activity nor the phosphorylation status of DNA-PKCS influences its initial accumulation. However, impairment of both of these functions results ...
DNA double-strand breaks (DSBs) can be repaired by homologous recombination (HR) or non-homologous end joining (NHEJ). The mechanisms that govern whether a DSB is repaired by NHEJ or HR remain unclear. Here, we characterise DSB repair in the amoeba Dictyostelium. HR is the principal pathway responsible for resistance to DSBs during vegetative cell growth, a stage of the life cycle when cells are predominantly in G2. However, we illustrate that restriction-enzyme-mediated integration of DNA into the Dictyostelium genome is possible during this stage of the life cycle and that this is mediated by an active NHEJ pathway. We illustrate that Dclre1, a protein with similarity to the vertebrate NHEJ factor Artemis, is required for NHEJ independently of DNA termini complexity. Although vegetative dclre1(-) cells are not radiosensitive, they exhibit delayed DSB repair, further supporting a role for NHEJ during this stage of the life cycle. By contrast, cells lacking the Ku80 component of the Ku heterodimer that
1. ChapmanJR, TaylorMR, BoultonSJ (2012) Playing the end game: DNA double-strand break repair pathway choice. Mol Cell 47: 497-510.. 2. LongheseMP, BonettiD, GueriniI, ManfriniN, ClericiM (2009) DNA double-strand breaks in meiosis: checking their formation, processing and repair. DNA Repair (Amst) 8: 1127-1138.. 3. SchatzDG, SwansonPC (2011) V(D)J recombination: mechanisms of initiation. Annu Rev Genet 45: 167-202.. 4. LieberMR (2010) The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem 79: 181-211.. 5. BétermierM, BertrandP, LopezBS (2014) Is non-homologous end-joining really an inherently error-prone process? PLoS Genet 10: e1004086.. 6. McVeyM, LeeSE (2008) MMEJ repair of double-strand breaks (directors cut): deleted sequences and alternative endings. Trends Genet 24: 529-538.. 7. TruongLN, LiY, ShiLZ, HwangPY, HeJ, et al. (2013) Microhomology-mediated End Joining and Homologous Recombination share the initial end resection step to ...
TY - JOUR. T1 - Evidence that unrejoined DNA double-strand breaks are not predominantly responsible for chromosomal radiosensitivity of AT fibroblasts. AU - Loucas, Bradford. AU - Cornforth, Michael. PY - 2004/11. Y1 - 2004/11. N2 - To examine more fully the nature of chromosomal radiosensitivity in ataxia telangiectasia (AT) cells, we employed 24-color combinatorial painting to visualize 137CS γ-ray-induced chromosome-type aberrations in cells of two AT and one normal primary human fibroblast strains irradiated in log-phase growth. As a measure of misrejoined radiation-induced DSBs, we quantified exchange breakpoints associated with both simple and complex exchanges. As a measure of unrejoined DSBs, we quantified breakpoints from terminal deletions as well as deletions associated with incomplete exchange. For each of these end points, the frequency of damage per unit dose was markedly higher in AT cells compared to normal cells, although the proportion of total breaks that remained unrejoined ...
TY - JOUR. T1 - Protein kinase CK2 localizes to sites of DNA double-strand break regulating the cellular response to DNA damage. AU - Olsen, Birgitte B.. AU - Wang, Shih Ya. AU - Svenstrup, Tina H.. AU - Chen, Benjamin P C. AU - Guerra, Barbara. PY - 2012/3/9. Y1 - 2012/3/9. N2 - Background: The DNA-dependent protein kinase (DNA-PK) is a nuclear complex composed of a large catalytic subunit (DNA-PKcs) and a heterodimeric DNA-targeting subunit Ku. DNA-PK is a major component of the non-homologous end-joining (NHEJ) repair mechanism, which is activated in the presence of DNA double-strand breaks induced by ionizing radiation, reactive oxygen species and radiomimetic drugs. We have recently reported that down-regulation of protein kinase CK2 by siRNA interference results in enhanced cell death specifically in DNA-PKcs-proficient human glioblastoma cells, and this event is accompanied by decreased autophosphorylation of DNA-PKcs at S2056 and delayed repair of DNA double-strand breaks.Results: In the ...
Expression of BCR-ABL oncoprotein in chronic myeloid leukemia (CML) promotes neoplastic transformation of hematopoietic stem cells through modulation of diverse pathways. CML is a multistep disease, which evolves as a chronic phase and progresses to blast crisis. This progression has been associated with the appearance and accumulation of new cytogenetic anomalies and mutations. The mechanisms underlying the genomic instability promoted by BCR-ABL remain obscure. Through comparative analysis of different DNA double-strand break (DSB) repair mechanisms as a function of the BCR-ABL status in human megakaryocytic and CML cell lines, we found that BCR-ABL upregulates error-prone DSB repair pathways [single-strand annealing (SSA) and non-homologous end joining] rather than the high-fidelity mechanism of homologous recombination. Intriguingly, expression analysis of DSB repair pathway choice determining factors revealed increased levels of the protein CtIP in BCR-ABL-positive cells, particularly in ...
Article Multicellular signalling model for DNA double-strand break repair kinetics after low-dose radiation. This paper introduces the Multicellular Signalling (MULTISIG1) model in which DNA double-strand break (DSB) repair initiation requires interc...
This unit describes immunocytochemical detection of phosphorylated histone H2AX for revealing the presence of DNA double-strand breaks. Double-strand breaks indicate DNA damage induced by ionizing radiation or by treatment with antitumor drugs such as DNA topoisomerase inhibitors. However, double-strand breaks can also be intrinsic, occurring in healthy, nontreated cells for a variety of reasons, and are generated in the course of DNA fragmentation in apoptotic cells. The unit presents strategies to distinguish radiation- or drug-induced breaks from those intrinsically formed in untreated cells or associated with apoptosis. The protocol describes the immunocytochemical detection of histone H2AX phosphorylated on Ser-139 combined with measurement of DNA content to identify cells that have DNA double-strand breaks and to concurrently assess their cell cycle phase. The detection is based on indirect immunofluorescence using a FITC-labeled secondary antibody, and DNA is counterstained with propidium ...
TY - JOUR. T1 - Estimating the number of double-strand breaks formed during meiosis from partial observation. AU - Toyoizumi, Hiroshi. AU - Tsubouchi, Hideo. PY - 2012/12/1. Y1 - 2012/12/1. N2 - Analyzing the basic mechanism of DNA double-strand breaks (DSB) formation during meiosis is important for understanding sexual reproduction and genetic diversity. The location and amount of meiotic DSBs can be examined by using a common molecular biological technique called Southern blotting, but only a subset of the total DSBs can be observed; only DSB fragments still carrying the region recognized by a Southern blot probe are detected. With the assumption that DSB formation follows a nonhomogeneous Poisson process, we propose two estimators of the total number of DSBs on a chromosome: (1) an estimator based on the Nelson-Aalen estimator, and (2) an estimator based on a record value process. Further, we compared their asymptotic accuracy.. AB - Analyzing the basic mechanism of DNA double-strand breaks ...
Initiation of meiotic recombination in the yeast Saccharomyces cerevisiae occurs by localized DNA double-strand breaks (DSBs) at several locations in the genome, corresponding to hot spots for meiotic gene conversion and crossing over. The meiotic DSBs occur in regions of chromatin that are hypersen …
TY - JOUR. T1 - Exo1 plays a major role in DNA end resection in humans and influences double-strand break repair and damage signaling decisions. AU - Tomimatsu, Nozomi. AU - Mukherjee, Bipasha. AU - Deland, Katherine. AU - Kurimasa, Akihiro. AU - Bolderson, Emma. AU - Khanna, Kum Kum. AU - Burma, Sandeep. N1 - Funding Information: We thank Dr. Woodring Wright and Dr. Matthew Porteus for critical comments on the manuscript. We are grateful to Dr. Cristina Cardoso (Max Delbruck Center for Molecular Medicine, Germany) for the GFP-RPA construct, to Dr. Randal Tibbetts (University of Wisconsin-Madison) for the GFP-ATR construct, and to Dr. Luciana Chessa (University La Sapienza, Italy) for the ATLD cells. We thank Cristel Camacho for generating the DsRed-Exo1 construct. We are grateful to Dr. David Chen for facilitating the laser micro-irradiation experiments. K.K. is supported by a Program grant from National Health and Medical Research Council, Australia . S.B. is supported by grants from the ...
TY - JOUR. T1 - DNA double-strand breaks. T2 - A potential causative factor for mammalian aging?. AU - Li, Han. AU - Mitchell, James R.. AU - Hasty, Paul. PY - 2008/7/1. Y1 - 2008/7/1. N2 - Aging is a pleiotropic and stochastic process influenced by both genetics and environment. As a result the fundamental underlying causes of aging are controversial and likely diverse. Genome maintenance and in particular the repair of DNA damage is critical to ensure longevity needed for reproduction and as a consequence imperfections or defects in maintaining the genome may contribute to aging. There are many forms of DNA damage with double-strand breaks (DSBs) being the most toxic. Here we discuss DNA DSBs as a potential causative factor for aging including factors that generate DNA DSBs, pathways that repair DNA DSBs, consequences of faulty or failed DSB repair and how these consequences may lead to age-dependent decline in fitness. At the end we compare mouse models of premature aging that are defective ...
CtIP helps maintain genomic stability by promoting DNA double-strand-break repair. Structural and biophysical analyses now show that the N terminus of human CtIP forms a tetrameric structure that is required for resection of broken DNA ends to permit their repair by homologous recombination. Mammalian CtIP protein has major roles in DNA double-strand break (DSB) repair. Although it is well established that CtIP promotes DNA-end resection in preparation for homology-dependent DSB repair, the molecular basis for this function has remained unknown. Here we show by biophysical and X-ray crystallographic analyses that the N-terminal domain of human CtIP exists as a stable homotetramer. Tetramerization results from interlocking interactions between the N-terminal extensions of CtIPs coiled-coil region, which lead to a dimer-of-dimers architecture. Through interrogation of the CtIP structure, we identify a point mutation that abolishes tetramerization of the N-terminal domain while preserving dimerization
DNA double-strand breaks (DSBs) and their repair can cause extensive epigenetic changes. As a result, DSBs have been proposed to promote transcriptional and, ultimately, physiological dysfunction via both cell-intrinsic and cell-non-autonomous pathways. Studying the consequences of DSBs in higher organisms has, however, been hindered by a scarcity of tools for controlled DSB induction. Here, we describe a mouse model that allows for both tissue-specific and temporally controlled DSB formation at ∼140 defined genomic loci. Using this model, we show that DSBs promote a DNA damage signaling-dependent decrease in gene expression in primary cells specifically at break-bearing genes, which is reversed upon DSB repair. Importantly, we demonstrate that restoration of gene expression can occur independently of cell cycle progression, underlining its relevance for normal tissue maintenance. Consistent with this, we observe no evidence for persistent transcriptional repression in response to a multi-day ...
Our study revealed that depletion of ataxin‐3 increases the levels of ubiquitylated MDC1, while at the same time reducing its residence time at DNA breaks, consistent with the idea that ubiquitylation of MDC1 is the primary signal that regulates its release from chromatin. Additionally, our findings reveal that ubiquitylation of MDC1 is regulated by ataxin‐3 in a manner that requires its catalytic activity. Notably, whereas ataxin‐3 depletion had a strong effect on the MDC1 exchange at sites of DNA damage, the net effect on the steady‐state accumulation of MDC1 at DSBs was subtle, similar to what has been found for RNF4 depletion (Galanty et al, 2012). This suggests that the rapid dissociation of MDC1 in the absence of ataxin‐3 is likely to be compensated by the instant recruitment of new MDC1 molecules, resulting in a dynamic cycle in which the residence time of individual molecules is severely reduced and insufficient to properly activate the response to DSBs. Consistent with this ...
DNA double‐strand breaks (DSBs) can be repaired by homologous recombination (HR), which uses undamaged homologous DNA sequences as a template for repair in a mostly error‐free manner. The first step in HR is the processing of DNA ends by 5′ to 3′ nucleolytic degradation (resection) to generate 3′‐ended single‐stranded DNA (ssDNA) that can invade a homologous template [1]. This ssDNA generation also induces activation of the DNA damage checkpoint, whose key players are the protein kinases ATM and ATR in mammals as well as their functional orthologs Tel1 and Mec1 in Saccharomyces cerevisiae [2].. Initiation of DSB resection requires the conserved MRX/MRN complex (Mre11/Rad50/Xrs2 in yeast; Mre11/Rad50/Nbs1 in mammals) that, together with Sae2, catalyses an endonucleolytic cleavage of the 5′ strands [3], [4], [5]. More extensive resection of the 5′ strands depends on two pathways, which require the 5′ to 3′ double‐stranded DNA exonuclease Exo1 and the nuclease Dna2 working ...
Genomic integrity is constantly challenged by DNA lesions, several thousands of which occur in each human cell every day. A particularly hazardous type of DNA lesion is the double-strand break (DSB),...
Featured Publications. EGFRvIII and DNA Double-Strand Break Repair: A Molecular Mechanism for Radioresistance in Glioblastoma B. Mukherjee, B. McEllin, C.V. Camacho, N. Tomimatsu, S. Sirasanagandala, S. Nannepaga, K.J. Hatanpaa, B. Mickey, C. Madden, E. Maher, D.A. Boothman, F. Furnari, W.K. Cavenee, R.M. Bachoo, and S. Burma Cancer Research May 2009 69 4252-4259. DNA-PK phosphorylates histone H2AX during apoptotic DNA fragmentation in mammalian cells. Mukherjee B, Kessinger C, Kobayashi J, Chen BP, Chen DJ, Chatterjee A, Burma S DNA Repair (Amst.) 2006 May 5 5 575-90. INT6/EIF3E controls the RNF8-dependent ubiquitylation pathway and facilitates DNA double-strand break repair in human cells. Morris C, Tomimatsu N, Burma S, Jalinot P Cancer Res. 2016 Aug EEPD1 Rescues Stressed Replication Forks and Maintains Genome Stability by Promoting End Resection and Homologous Recombination Repair. Wu Y, Lee SH, Williamson EA, Reinert BL, Cho JH, Xia F, Jaiswal AS, Srinivasan G, Patel B, Brantley A, Zhou D, ...
Fe65 adapter protein that forms a transcriptionally active complex with the gamma-secretase-derived amyloid precursor protein (APP) intracellular domain. Plays a central role in the response to DNA damage by translocating to the nucleus and inducing apoptosis. May act by specifically recognizing and binding histone H2AX phosphorylated on Y142 (H2AXpY142) at double-strand breaks (DSBs), recruiting other pro-apoptosis factors such as JNK1. Required for histone H4 acetylation at double-strand breaks (DSBs). Its ability to specifically bind modified histones and chromatin modifying enzymes such as TIP60, probably explains its trancription activation activity. Note: This description may include information from UniProtKB ...
An episomal DNA vector (YpJA18), encoding two selectable recombinant yeast genes ( TRP1, URA3), was constructed to assess the fidelity of DNA repair in haploid repair-competent ( RAD) wild-type yeast
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Conditions leading to unrepaired DNA double-stranded breaks are potent inducers of genetic instability. Systemic conditions may lead to fluctuation of hydrogen ions in the cellular microenvironment and we show that small variations in extracellular pH, termed suboptimal pHe, can decrease the efficiency of DNA repair in the absence of intracellular pH variation. Recovery from bleomycin-induced DNA double-stranded breaks in fibroblasts proceeded less efficiently at suboptimal pHe values ranging from 7.2 to 6.9, as shown by the persistence of repair foci, reduction of H4K16 acetylation and chromosomal instability, while senescence or apoptosis remained undetected. By allowing escape from these protective mechanisms, suboptimal pHe may therefore enhance the genotoxicity of double-stranded breaks, leading to genetic instability. ...
In this study, we show that DSB rejoining in mammalian cells can be classified into two categories: the rejoining of correct, i.e., formerly connected, break ends leading to restriction fragment reconstitution and the joining of ends from different DSBs, which generates genomic rearrangements. The probability with which a break end is either joined to a correct or an incorrect break end depends upon the spatial proximity of the DSBs. If no other DSBs are nearby at the time of repair, the broken ends are likely to be rejoined to their correct end. The presence of multiple DSBs at the same time enhances misrejoining in repair-proficient cells. To investigate the pathway mediating the formation of genomic rearrangements, it is necessary to choose conditions in which wild-type cells exhibit rearrangements by the appearance of aberrant restriction fragments. Such conditions necessitate relatively high radiation doses. However, under the conditions examined, the capacity for DSB rejoining is not ...
DNA can be damaged in many ways. Consequently, there are numerous mechanisms to repair it. It is a fascinating field full of innovative concepts (DNA repair was my favorite course during my undergrad studies). Double strand breaks (DSBs) are considered the most genotoxic, which is why many DNA damaging drugs and treatments intended to treat cancer…
Exploitation of custom-designed nucleases to induce DNA double-strand breaks (DSBs) at genomic locations of choice has transformed our ability to edit genomes, regardless of their complexity. DSBs can trigger either error-prone repair pathways that induce random mutations at the break sites or preci …
The Artemis nuclease acknowledges and endonucleolytically cleaves at single-stranded to double-stranded DNA (ss/dsDNA) boundaries. It can also be a key enzyme in the non-homologous finish becoming a member of (NHEJ) DNA double-strand break restore pathway. Previously, a truncated type, Artemis-413, was developed thats constitutively energetic each in vitro and in vivo. Here, we use this constitutively energetic type of Artemis to detect DNA constructions with ss/dsDNA boundaries that come up below topological stress. Topoisomerases stop irregular ranges of torsional stress by means of modulation of constructive and detrimental supercoiling. We present that overexpression of Artemis-413 in yeast cells carrying genetic mutations that ablate topoisomerase exercise have an elevated frequency of DNA double-strand breaks (DSBs). Based on the biochemical exercise of Artemis, this implies a rise in ss/dsDNA-containing constructions upon elevated torsional stress, with DSBs arising because of Artemis ...
Repair of DNA double strand breaks (DSB), either by homologous recombination (HR) or nonhomologous end-joining (NHEJ), is essential to maintain genomic stability. To examine the impact of NHEJ deficiency on genomic integrity in Ku80 null (Ku-) mice, the chromosomally integrated shuttle vector pUR288, which includes a lacZ reporter gene, was used to measure mutations in vivo. Unexpectedly, a significant decrease was found in mutant frequencies of Ku- liver (5.04x10(-5)) and brain (4.55x10(-5)) compared to tissues obtained from normal (Ku+) littermates (7.92x10(-5)and 7.30x10(-5), respectively). No significant difference was found in mutant frequencies in spleen from Ku- (7.21x10(-5)) and Ku+ mice (8.16x10(-5)). The determination of the mutant spectrum in lacZ revealed the almost complete absence of chromosomal rearrangements (R) in Ku- tissues (0.5%, 3/616), a notable distinction from Ku+ controls (16.7%, 104/621). These findings suggest that accurate repair of DSB by HR and elimination of cells ...
As G4 motif requirements for G4 structure formation are known, it was possible to identify the locations of G4 motifs in whole genomes using computational tools. They are enriched at specific regions such as telomeres, promoters, mitotic and meiotic double strand break (DSB) sites, and origins of replication (1-3). Accordingly, G4 structures could be involved in telomere maintenance, (post-)transcriptional regulation, or meiotic DSB formation (Figure 1a-e). To date, it is not known if G4 structures are relevant for one or several of these biological processes. Furthermore, the specific function of identified G4 structures in these processes is still not understood. The current model is that it is unlikely that all G4s will have the same function in the cell. It is postulated that specific G4 structures form upon certain trigger events, such as transcription or meiosis, and some only under certain conditions, such as stress. In the current model, G4 structures are key regulatory elements that ...
Ionizing radiation has a number of harmful effects in humans. The most important among these is the induction of cancer. It is assumed that damage to DN
Université de Liège - ULiège , Département des sciences de la vie , GIGA-R : Virologie - Immunologie - Département des sciences de la vie - GIGA-Research ,] ...
1F2U: Structural biology of Rad50 ATPase: ATP-driven conformational control in DNA double-strand break repair and the ABC-ATPase superfamily.
Chk1 and Chk2 are differentially involved in homologous recombination repair and cell cycle arrest in response to DNA double-strand breaks induced by camptothecins ...
Fingerprint Dive into the research topics of Visualization of irreparable ischemic damage in brain by selective labeling of double-strand blunt-ended DNA breaks. Together they form a unique fingerprint. ...
Comparative study of kinetics on DNA double-strand break induced by photo- and gamma-irradiation: Protective effect of water-soluble flavonoids ...
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Daily News How Gaining and Losing Weight Affects the Body Millions of measurements from 23 people who consumed extra calories every day for a month reveal changes in proteins, metabolites, and gut microbiota that accompany shifts in body mass.. ...
Double-strand break (DSB) repair is essential for cell survival and for the maintenance of genome integrity. In this study, we utilized I-Sce I, an endonuclease from yeast with an 18-bp recognition site to introduce DSB ...
The shortcut is. Alt + Enter. To insert a line break within a cell hold down the Alt key (next to your space bar) and press Enter. This inserts a fixed line break within the cell.. This operates differently to the Wrap Text format. Wrap Text will break depending on the length of the words and the width of the column.. The Alt + Enter method will break in the spot you added Alt + Enter providing the column is wide enough. This method is ideal for data lists that require a single heading row. Instead of using two rows for the headings (not a good practice) you can use one row and get the same effect as two rows.. ...
This test has been cleared or approved by the U.S. Food and Drug Administration and is used per manufacturers instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements ...
Acne. I know Im not the only one who considers it the bane of their existence sometimes. When you break out (or at least when I break out) you tend to blame
From farm stays and bushwalking to pampering with champers and sports weekends, over 10 top tips for planning and enjoying a short break. Learn more.
just wanted to let everybody know in case someone thinks im missing. i ll try again to take a break from the DF for some time.. lets see if i can make it :)
A thermal break is an element of low conductivity thats placed between any two materials to try to stop or slow down the transfer...
There are many reasons why taking a break is important. But did you know that doing so can actually boost your productivity and success?
When it comes to healthy dinner ideas, youve been in the groove for a while now. These seven swaps can help you change it up and break out of a rut.
Michelle Janssen always struggled to relax, but when thoughts of catastrophe began popping into her head regularly, it exposed a much bigger problem.
bool MathStructure::isolate_x_sub(....) { .... for(size_t i = 0; i , mvar-,size(); i++) { if((*mvar)[i].contains(x_var)) { mvar2 = &(*mvar)[i]; if(mvar-,isMultiplication()) { for(size_t i2 = 0; i , mvar2-,size(); i2++) { if((*mvar2)[i2].contains(x_var)) {mvar2 = &(*mvar2)[i2]; break;} } } break ...
Often as coaches, we find ourselves replicating methods merely because others have had success with them. The prime example is the block
ТРЕКИ 2017: Skaarj - Afterworld (Breaks) NFBmusic youtu.be/6E1QFh8FRPM Skaarj - Origin (Breaks) NFBmusic youtu.be/SdXi4m2hPlU
OCLC 60932736.CS1 maint: multiple names: authors list (link) White, Ryan R.; Vijg, Jan (2016). "Do DNA Double-Strand Breaks ... DNA replication checkpoints are located at the G1, S and G2 phase to check if DNA is normal, and withdraws the cell from cycle ... appearing in their DNA. Therefore, the wearing off of DNA would not occur, and the genetic information would remain the same, ... The DNA structure in these organisms are in the form of circular chromosomes, meaning there would be no "ends" ...
CSB also accumulates at sites of DNA double-strand breaks in a transcription dependent manner and influences double-strand ... Batenburg NL, Thompson EL, Hendrickson EA, Zhu XD (2015). "Cockayne syndrome group B protein regulates DNA double-strand break ... CSB protein facilitates homologous recombinational repair of double-strand breaks and represses non-homologous end joining. In ... double-strand breaks > monoadducts > oxidative damages. The CSB protein interacts with SNM1A(DCLRE1A) protein, a 5'- 3' ...
Van Gent, D. C.; Hoeijmakers, J. H.; Kanaar, R (2001). "Chromosomal stability and the DNA double-stranded break connection". ... For example, a mutation in a caretaker gene coding for a DNA repair pathway that leads to the inability to properly repair DNA ... and other actions that ensure cell survival following DNA damage. Specific DNA maintenance operations encoded by caretaker ... The process of DNA replication inherently places cells at risk of acquiring mutations. Thus, caretaker genes are vitally ...
July 2010). "Targeting DNA Double-Strand Breaks with TAL Effector Nucleases". Genetics. 186 (2): 757-761. doi:10.1534/genetics. ... ZFNs can be used to disable dominant mutations in heterozygous individuals by producing double-strand breaks (DSBs) in the DNA ... It has been demonstrated in human cells that ZFNs can direct double-strand breaks (DSBs) to CAG repeats and shrink the repeat ... Such off-target cleavage may lead to the production of enough double-strand breaks to overwhelm the repair machinery and, as a ...
Detection, repair and signalling of DNA double-strand breaks". Biochemical Society Transactions. 27 (2): 1-13. doi:10.1042/ ... Lilley, D. M. (1983). "Structural perturbation in supercoiled DNA: Hypersensitivity to modification by a single-strand- ... Brownlee, G. G. (1979). "The Fourteenth Colworth Medal Lecture Sequencing eukaryotic genes or the anatomy of DNA". Biochemical ... Dillingham, M. S. (2011). "Superfamily I helicases as modular components of DNA-processing machines". Biochemical Society ...
A linear dose-response relationship has been observed between x-ray dose and double-strand breaks in DNA in human sperm. ... Singh, NP; Stephens, RE (January 1998). "X-ray induced DNA double-strand breaks in human sperm". Mutagenesis. 13 (1): 75-9. doi ... Travis, Alan (January 4, 2009). "New scanners break child porn laws". The Guardian. London. Archived from the original on 6 ... the energy being emitted by a backscatter X-ray is a type of ionizing radiation that breaks chemical bonds. Ionizing radiation ...
... cleaves DNA via a staggered DNA double-stranded break. Out of 16 Cpf1-family proteins, scientists identified two candidate ... consisting a of 2-6 base pair DNA sequence immediately following the DNA sequence targeted by the Cas9 nuclease in the CRISPR ... A transcription factor or promoter factor is a protein that controls the rate of transcription of genetic information from DNA ... to messenger RNA, by binding to a specific DNA sequence.. ...
During nuclear membrane rupture events, DNA double-strand breaks occur. Thus the survival of cells migrating through confined ... In mammals, the nuclear membrane can break down within minutes, following a set of steps during the early stages of mitosis. ... During the G2 phase of interphase, the nuclear membrane increases its surface area and doubles its number of nuclear pore ... In other eukaryotes (animals as well as plants), the nuclear membrane must break down during the prometaphase stage of mitosis ...
Examples are direct and indirect inhibitors on DNA double-strand breaks. Direct inhibitors target proteins (PARP family) and ... Direct radiation creates a free DNA radical from radiation energy deposition that damages DNA. Indirect radiation occurs from ... In this case, cells are able to replicate without repair of their DNA, prone to incidence of cancer. Most cells are in G1 and S ... G1 arrest delays repair mechanism before synthesis of DNA in S phase and mitosis in M phase, suggesting key checkpoint to lead ...
... surrounding a double-strand break in DNA, is needed for repair of the double-strand break. Phosphorylation of methylpurine DNA ... Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM (March 1998). "DNA double-stranded breaks induce histone H2AX ... When serine 337 is phosphorylated by protein kinase A in vitro, the DNA binding efficiency of the p50 subunit of NF-κB is ... Eukaryotic DNA is organized with histone proteins in specific complexes called chromatin. The chromatin structure functions and ...
... s serve as stimulators of DNA double-strand break repair in bacteria, which can arise from radiation or chemical ... "strand invasion," in which one strand of a homologous double-stranded DNA is displaced by the RecA-associated ssDNA. Strand ... 2008). RecBCD enzyme and the repair of double-stranded DNA breaks. Microbiol Mol Biol Rev. 72(4): 642-671. PMID 19052323 ... ended strand to cutting the 5'-ended strand. In either case the resulting 3' single-stranded DNA (ssDNA) is bound by multiple ...
Exposed chromosome ends are interpreted as double-stranded breaks (DSB) in DNA; such damage is usually repaired by reattaching ... TERT is a reverse transcriptase, which is a class of enzyme that creates single-stranded DNA using single-stranded RNA as a ... However, the genes that have mutated in these diseases all have roles in the repair of DNA damage and the increased DNA damage ... Telomerase allows each offspring to replace the lost bit of DNA, allowing the cell line to divide without ever reaching the ...
DNA double-strand breaks can be repaired during interphase by two principal processes. The first process, non-homologous end ... Shibata A (2017). "Regulation of repair pathway choice at two-ended DNA double-strand breaks". Mutat Res. 803-805: 51-55. doi: ... is more accurate than NHEJ in repairing double-strand breaks. HRR is active during the S and G2 phases of interphase when DNA ... can join the two broken ends of DNA in the G1, S and G2 phases of interphase. The second process, homologous recombinational ...
"Search-and-replace genome editing without double-strand breaks or donor DNA". Nature. 576 (7785): 149-157. Bibcode:2019Natur. ... Targeting human RNA after it has been transcribed from DNA, rather than DNA, would allow for more temporary effects than ... 1972 - The DNA composition of chimpanzees and gorillas is discovered to be 99% similar to that of humans. 1973 - Stanley Norman ... "Scientists use mushroom DNA to produce permanently-glowing plants". New Atlas. 28 April 2020. Archived from the original on 9 ...
They recognize damage sites through deformation of double stranded DNA (dsDNA) secondary structure. During DNA replication, DNA ... Double-strand breaks, both intentional and unintentional, regularly occur in cells. Unintentional breaks are commonly generated ... Both cases require the ends in double strand breaks be processed by nucleases before repair can take place. One such nuclease ... V(D)J recombination involves opening stem-loops structures associated with double-strand breaks and subsequently joining both ...
Fiedler, Anja; Reinert, Tilo; Tanner, Judith; Butz, Tilman (July 2007). "DNA double strand breaks and Hsp70 expression in ... "Enhanced DNA double-strand break repair of microbeam targeted A549 lung carcinoma cells by adjacent WI38 normal lung fibroblast ... At the time it was believed that radiation damage to cells was entirely the result of damage to DNA. Charged particle ...
Cann KL, Hicks GG (December 2007). "Regulation of the cellular DNA double-strand break response". Biochemistry and Cell Biology ... Xu Z, Zan H, Pone EJ, Mai T, Casali P (June 2012). "Immunoglobulin class-switch DNA recombination: induction, targeting and ...
October 2010). "Targeting DNA double-strand breaks with TAL effector nucleases". Genetics. 186 (2): 757-61. doi:10.1534/ ... "Ku regulates the non-homologous end joining pathway choice of DNA double-strand break repair in human somatic cells". PLOS ... have high transduction rates and have a unique property of stimulating endogenous HR without causing double strand DNA breaks ... December 2009). "Breaking the code of DNA binding specificity of TAL-type III effectors". Science. 326 (5959): 1509-12. Bibcode ...
"Targeting DNA double-strand breaks with TAL effector nucleases". Genetics. 186 (2): 757-61. doi:10.1534/genetics.110.120717. ... Genome editing uses artificially engineered nucleases that create specific double-stranded breaks at desired locations in the ... up-taken DNA can either integrate with the genome or exist as extrachromosomal DNA. DNA is generally inserted into animal cells ... "Simian virus 40 DNA sequences in DNA of healthy adult mice derived from preimplantation blastocysts injected with viral DNA". ...
"Targeting DNA double-strand breaks with TAL effector nucleases". Genetics. 186 (2): 757-61. doi:10.1534/genetics.110.120717. ... Gene targeting techniques, which creates double-stranded breaks and takes advantage on the cells natural homologous ... DNA is generally inserted into animal cells using microinjection, where it can be injected through the cell's nuclear envelope ... In plants the DNA is often inserted using Agrobacterium-mediated recombination, biolistics or electroporation. As only a single ...
July 2010). "TAL Effector Nucleases Create Targeted DNA Double-strand Breaks". Genetics. 186 (2): 757-61. doi:10.1534/genetics. ... hybrid nuclease with novel DNA binding specificity creates double-strand breaks". Proceedings of the National Academy of ... The TAL-DNA code was broken by two separate groups in 2010. The first group, headed by Adam Bogdanove, broke this code ... December 2009). "Breaking the code of DNA binding specificity of TAL-type III effectors". Science. 326 (5959): 1509-12. Bibcode ...
... based methods of identifying DNA double-strand breaks (DSBs) by labeling DNA repair proteins, BLESS utilizes biotinylated DNA ... Use of biotinylated DNA linkers designed to specifically recognize double-stranded DNA breaks allows for a less biased, more ... Aparicio T, Baer R, Gautier J (July 2014). "DNA double-strand break repair pathway choice and cancer". DNA Repair. 19: 169-75. ... Bouwman BA, Crosetto N (December 2018). "Endogenous DNA Double-Strand Breaks during DNA Transactions: Emerging Insights and ...
RAD51 maintains genome integrity by repairing DNA double-strand breaks through homologous recombination. RAD51 heterozygous ...
Homologous recombination (HR) is an accurate process for repairing DNA double-strand breaks. HR is nearly absent in G1 phase, ... a less accurate and more mutagenic process for repairing double strand breaks, is active throughout the cell cycle. Cellular ... Thus, during this phase, the amount of DNA in the cell has doubled, though the ploidy and number of chromosomes are unchanged. ... If the DNA is damaged, p53 will either repair the DNA or trigger the apoptosis of the cell. If p53 is dysfunctional or mutated ...
However, double-stranded DNA breaks are much more difficult to repair, and can lead to dramatic chromosomal abnormalities and ... Cells have mechanisms for repairing single-strand DNA damage and double-stranded DNA damage. ... Targeting double-stranded breaks increases the probability that cells will undergo cell death. Cancer cells are generally less ... of tumor oxygen supply because these particles act mostly via direct energy transfer usually causing double-stranded DNA breaks ...
DNA double-strand breaks can be repaired during interphase by two principal processes. The first process, non-homologous end ... ISBN 978-0-07-325839-3. Shibata A. Regulation of repair pathway choice at two-ended DNA double-strand breaks. Mutat Res. 2017 ... The second process, homologous recombinational repair (HRR), is more accurate than NHEJ in repairing double-strand breaks. ... Synthesis (S), in which the cell synthesizes its DNA and the amount of DNA is doubled but the number of chromosomes remains ...
"Repair of HZE-particle-induced DNA double-strand breaks in normal human fibroblasts". Radiation Research. 169 (4): 437-46. ... The double-detriment life-table approach is what is recommended by the NPRC to measure radiation cancer mortality risks. The ... Doubling Dose for 20 Years Following Exposure - Provides a roughly equivalent comparison based on life-loss from other ... to differences between space radiation and x-rays dependence of risk on dose-rates in space related to the biology of DNA ...
This complex functions in homologous recombination and repair of DNA double-strand breaks. Inherited mutations in MCM8 and MCM9 ... The germline MCM8-MCM9 protein complex is most likely required for the resolution of double-strand breaks that occur during ... Epigenetic alterations often occur in association with the DNA repair defect, and such alterations likely have a role in the ... Chromosome instability syndromes due to impaired DNA repair and with features of neurodegeneration and epigenetic alteration ...
... (also known as Mcd1, Scc1, KIAA0078, NXP1, HR21), an essential gene, encodes a DNA double-strand break (DSB) repair ... Unal E, Heidinger-Pauli JM, Koshland D (July 2007). "DNA double-strand breaks trigger genome-wide sister-chromatid cohesion ... September 1996). "Sequence conservation of the rad21 Schizosaccharomyces pombe DNA double-strand break repair gene in human and ... "Sequence conservation of the rad21 Schizosaccharomyces pombe DNA double-strand break repair gene in human and mouse". Genomics ...
DNA repair mechanism and/or the synthesis dependent strand annealing mechanism for repairing double strand breaks in DNA (see ... clinical manifestation of defective response to DNA double-strand breaks". DNA Repair (Amst). 3 (8-9): 1207-17. doi:10.1016/j. ... a process that accurately repairs double-strand breaks, both in somatic cells and during meiosis.[citation needed] There is no ... when there are errors in the cell DNA (2) to interact with FANCD2 that can activate the BRCA1/BRCA2 pathway of DNA repair. This ...
Segments with labels on the inside reside on the B strand of DNA, segments with labels on the outside are on the A strand. ... The results of the microscopy experiments led to the idea that chloroplast DNA replicates using a double displacement loop (D- ... the branched and complex structures seen in cpDNA experiments are real and not artifacts of concatenated circular DNA or broken ... DNA becomes susceptible to deamination events when it is single stranded. When replication forks form, the strand not being ...
In biology, a probe is a single strand of DNA or RNA that is complementary to a nucleotide sequence of interest. ... This technique is sometimes called "break-apart FISH". Single-molecule RNA FISH[edit]. Single-molecule RNA FISH, also known as ... This variation is often called double-fusion FISH or D-FISH. In the opposite situation-where the absence of the secondary color ... Probe size is important because longer probes hybridize less specifically than shorter probes, so that short strands of DNA or ...
single-stranded DNA-dependent ATPase activity. Cellular component. • cytoplasm. • site of double-strand break. • PML body. • ... In double-strand break repair[edit]. Double-strand break (DSB) repair by homologous recombination is initiated by 5' to 3' ... replication-born double-strand break repair via sister chromatid exchange. • cellular response to DNA damage stimulus. • strand ... single-stranded DNA binding. • double-stranded DNA binding. • ...
... can be infected by double-stranded DNA viruses that are unrelated to any other form of virus and have a variety of ... Methanogens also play a critical role in the carbon cycle, breaking down organic carbon into methane, which is also a major ... For example, thermostable DNA polymerases, such as the Pfu DNA polymerase from Pyrococcus furiosus, revolutionized molecular ... "Archaeal virus with exceptional virion architecture and the largest single-stranded DNA genome". Proceedings of the National ...
Jacqueline Fell, Adam Longo, Kelli Cook 20: Casey Anthony's defense begins case, challenges DNA evidence[dead link], Central ... Four hundred pieces of evidence were presented.[12] A strand of hair was recovered from the trunk of Casey's car which was ... Day 31: George Anthony breaks down, jury hears from Kronk's son, grief expert Archived 2011-09-01 at the Wayback Machine., ... and other news channels deciding to focus on the trial saw their ratings double and triple.[134] HLN achieved its most watched ...
Bekker-Jensen S, Mailand N (Dec 2010). "Assembly and function of DNA double-strand break repair foci in mammalian cells". DNA ... is a marker for DNA double strand breaks,[82] and forms part of the response to DNA damage.[36][83] H2AX is phosphorylated ... Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM (Mar 1998). "DNA double-stranded breaks induce histone H2AX phosphorylation ... "Megabase chromatin domains involved in DNA double-strand breaks in vivo". The Journal of Cell Biology. 146 (5): 905-16. doi: ...
Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans. Science Translational ... www.intechopen.com/books/dna-repair/meiosis-as-an-evolutionary-adaptation-for-dna-repair (页面存档备份,存于互联网档案馆) ... Harris Bernstein, Carol Bernstein and Richard E. Michod (2011). Meiosis as an Evolutionary Adaptation for DNA Repair. Chapter ... 19 in DNA Repair. Inna Kruman editor. InTech Open Publisher. doi:10.5772/25117 http:// ...
"for his discovery of آران‌ای سرکوبگر - gene silencing by double-stranded RNA"[۷۹] ... "for ground-breaking experimental methods that enable measuring and manipulation of individual quantum systems"[۱۱۹] ... "for his fundamental studies of the biochemistry of nucleic acids, with particular regard to recombinant-DNA"[۲۹] ...
... predominantly use homologous recombination to repair double-strand DNA breaks". 》Stem Cells and Development》 19 (11): 1699-1711 ... DNA 손상 복구[편집]. 분화된 체세포와 배아줄기세포는 DNA 손상을 처리하기 위해 다른 전략을 사용한다. 예를 들어, 체세포의 한 유형인 인간 포피 섬유 아세포는 모든 세포주기 단계에서 이중 가닥 파손을 복구하기 위한 ... 결과적으로, DNA 손상을 정확하게 복구하기 위해서는 배아줄기세포에서 강력한 메커니즘이 필요하고, 복구가 실패하면 DNA가 손상된 그 세포를 제거하는 것이 필요하다. 따라서, 마우스 배아줄기세포는 주로 이중 가닥 파손을 고치기 ... 오히려 그들은 DNA 손상에 대한 반응으로 프로그램된 세포 사멸(apoptosis)을 겪는다.[24] 세포 사멸은 돌연변이와 암 진행을 방지하기 위해서 DNA 손상된 세포를 제거하는 이중 안전 장치 전략으로 사용될 수 ...
... to denature the double-stranded DNA. The denaturation in an alkaline environment may improve binding of the negatively charged ... This depurinates the DNA fragments, breaking the DNA into smaller pieces, thereby allowing more efficient transfer from the gel ... thymine residues of DNA to a positively charged amino groups of membrane, separating it into single DNA strands for later ... A Southern blot is a method used in molecular biology for detection of a specific DNA sequence in DNA samples. Southern ...
In wild-type S. cerevisiae, DNA damage rates increased 3-fold with age, but more than 5-fold in mutants deleted for either the ... It was the first SOD whose atomic-detail crystal structure was solved, in 1975.[8] It is an 8-stranded "Greek key" beta-barrel ... double-blinding, or placebo.[50] Superoxide dismutase is known to reverse fibrosis, possibly through de-differentiation of ... as all ingested SOD is broken down into amino acids before being absorbed. However, ingestion of SOD bound to wheat proteins ...
... inducing double-strand DNA breaks which, when repaired, could result in a cell homozygous for one of the two alleles. After ... "Every Cell in Your Body Has the Same DNA. Except It Doesn't". The New York Times. 21 May 2018. Archived from the original on 23 ... the defect in RecQ an helicase facilitates the defective unwinding of DNA during replication and is thus associated with the ... Other endogenous factors can also lead to mosaicism including mobile elements, DNA polymerase slippage, and unbalanced ...
The overall structure of RNA and DNA are immensely similar-one strand of DNA and one of RNA can bind to form a double helical ... The chemical properties of RNA make large RNA molecules inherently fragile, and they can easily be broken down into their ... This forces an RNA double helix to change from a B-DNA structure to one more closely resembling A-DNA. ... Main articles: RNA and DNA. The major difference between RNA and DNA is the presence of a hydroxyl group at the 2'-position of ...
Toll-like receptors are located in the endosomal membrane and recognize double-stranded RNA (dsRNA), MDA5 and RIG-I receptors ... that attack and destroy specific regions of the viral DNA of invading bacteriophages. Methylation of the host's own DNA marks ... which are released following a contusion or other injury that breaks through the first-line physical barrier (not to be ...
"The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway". Annu. Rev. Biochem. 79: 181-211 ... consequences for the repair of DNA double-strand breaks". Blood 112 (4): 1413-23. PMC 2967309. PMID 18524993. doi:10.1182/blood ... "Deregulation of DNA double-strand break repair in multiple myeloma: implications for genome stability". PLoS ONE 10 (3): ... "Targeting abnormal DNA double-strand break repair in tyrosine kinase inhibitor-resistant chronic myeloid leukemias". Oncogene ...
... which inhibits the religation of single-stranded DNA breaks generated by topoisomerase I; lethal double-stranded DNA breaks ... Topoisomerase I is an enzyme that mediates reversible single-strand breaks in DNA during DNA replication. ... occur when the topoisomerase I-DNA complex is encountered by the DNA replication machinery, DNA replication is disrupted, and ... Belotecan blocks topoisomerase I with a pIC50 of 6.56,[4] stabilizing the cleavable complex of topoisomerase I-DNA, ...
RNA tends to be single stranded but in special cases it is double.[64] Unusually for a virus, its genome is not a single piece ... The sequencing of the influenza genome and recombinant DNA technology may accelerate the generation of new vaccine strains by ... since almost the entire indigenous population of the Antilles was killed by an epidemic resembling influenza that broke out in ...
... a double strand break in DNA can initiate unprogrammed epigenetic gene silencing both by causing DNA methylation as well as by ... "Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG ... 5-Methylcytosine performs much like a regular cytosine, pairing with a guanine in double-stranded DNA. However, some areas of ... If this enzyme reaches a "hemimethylated" portion of DNA (where 5-methylcytosine is in only one of the two DNA strands) the ...
Basic research on the maturation of sperm shows that hyaluronan-binding sperm are more mature and show fewer DNA strand breaks ... double-blinded and randomized controlled trial." Human reproduction 28(2):306-14 (2013) ... A systematic meta-analysis of 24 estimates of DNA damage based on a variety of techniques concluded that sperm DNA damage ... However, potential factors that may influence pregnancy rates (and live birth rates) in ICSI include level of DNA fragmentation ...
The methylation of histone lysine has an important role in choosing the pathway for repairing DNA double-strand breaks.[21] As ... "The Dot1 histone methyltransferase and the Rad9 checkpoint adaptor contribute to cohesin-dependent double-strand break repair ... Often, the β-strands found in the pre-SET domain will form β-sheets with the β-strands of the SET domain, leading to slight ... The genomic DNA of eukaryotes associates with histones to form chromatin.[8] The level of chromatin compaction depends heavily ...
The non-covalent interactions between antiparallel strands in DNA can be broken in order to "open" the double helix when ... Altan-Bonnet, Grégoire; Libchaber, Albert; Krichevsky, Oleg (1 April 2003). "Bubble Dynamics in Double-Stranded DNA". Physical ... Antiparellel strands in DNA double helices are non-covalently bound by hydrogen bonding between Watson and Crick base pairs;[27 ... For example, DNA strands denatured with alkaline agents such as NaOH renature as soon as phosphate buffer is added.[21] ...
H3K36me3 is required for homologous recombinational repair of DNA double-strand breaks, and H4K20me2 facilitates repair of such ... Together with similar modifications such as DNA methylation it is part of the epigenetic code.[1] Histones associate with DNA ... The histone code is a hypothesis that the transcription of genetic information encoded in DNA is in part regulated by chemical ... The hypothesis is that chromatin-DNA interactions are guided by combinations of histone modifications. While it is accepted ...
In addition, during repair of DNA double-strand breaks, or repair of other DNA damages, incompletely cleared sites of repair ... "Double Strand Breaks Can Initiate Gene Silencing and SIRT1-Dependent Onset of DNA Methylation in an Exogenous Promoter CpG ... DNA repair deficiency in NSCLC[edit]. Deficiencies in DNA repair underlie many forms of cancer.[21] If DNA repair is deficient ... Epigenetic promoter methylation in DNA repair genes in NSCLC Gene Frequency of hyper- (or hypo-) methylation DNA repair pathway ...
Another example is DNA polymerase. It reads an intact DNA strand and uses it as a template to make a new strand. ... They break down other enzymes and proteins back into amino acids.[3] Nucleases are enzymes that cut DNA or RNA, often in ... Lyases: split chemical bonds, and often add double bond or ring structure ... It breaks down starch molecules into smaller glucose and maltose molecules. Another kind of enzyme is lipase. It breaks down ...
... the molecular switch of double-strand break repair". International Journal of Proteomics. 2011: 373816. doi:10.1155/2011/373816 ... If damaged DNA is left unrepaired, it can lead to cell death or genomic instability, cancer and other pathologies.[23] ... In response to DNA damage, the kinase domain of one monomer phosphorylates ser-1981 of the other interacting ATM, resulting in ... The activated ATM triggers a sequence of events including cell cycle arrest which allows time for the repair of the damaged DNA ...
... this method allowed purified samples of double-stranded DNA to be used without further cloning. This method's use of ... end of the DNA and purification of the DNA fragment to be sequenced. Chemical treatment then generates breaks at a small ... large DNA fragments into shorter DNA fragments. The fragmented DNA may then be cloned into a DNA vector and amplified in a ... Testing DNA is a technique which can detect specific genomes in a DNA strand to produce a unique and individualized pattern. ...
... or double-strand breaks into DNA, reducing the tension in the DNA strand. This allows the normal unwinding of DNA to occur ... When the DNA double-strand helix is unwound, during DNA replication or transcription, for example, the adjacent unopened DNA ... This prevents DNA replication and transcription, causes DNA strand breaks, and leads to programmed cell death (apoptosis). ... If the cell tries to replicate crosslinked DNA during cell division, or tries to repair it, the DNA strands can break. This ...
"Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG ... CpG, "-C-phosphate-G-" nucleotides on one DNA strand (left), and complementary C-G base-paring on two DNA strands (right) ... DNA damage appears to be the primary underlying cause of cancer.[39][40] If accurate DNA repair is deficient, DNA damages tend ... This methylation helps distinguish the newly synthesized DNA strand from the parent strand, which aids in the final stages of ...
For some applications such as double-clad fibers another form is preferred.[71] In fiber lasers based on double-clad fiber, an ... 41] In 2009, Bell Labs broke the 100 (petabit per second)×kilometer barrier (15.5 Tbit/s over a single 7,000 km fiber).[42] ... In 1981, General Electric produced fused quartz ingots that could be drawn into strands 25 miles (40 km) long.[24] ... Even simple cleaving (breaking) of the ends of the fiber can provide nicely flat surfaces with acceptable optical quality. ...
Double-stranded breaks in DNA are important threats to genome integrity because they can result in chromosomal aberrations that ... Chromosomal stability and the DNA double-stranded break connection.. van Gent DC1, Hoeijmakers JH, Kanaar R. ... Recently, unexpected links between these double-stranded break-repair systems, and several human genome instability and cancer ... Now, interactions between both double-stranded break-repair pathways and other cellular processes, such as cell-cycle ...
Loss of REV7 is shown to regulate end resection of double-stranded DNA breaks in BRCA1-deficient cells, leading to PARP ... Loss of REV7 is shown to regulate end resection of double-stranded DNA breaks in BRCA1-deficient cells, leading to PARP ... DNA-binding and strand-annealing activities of human Mre11: implications for its roles in DNA double-strand break repair ... REV7 counteracts DNA double-strand break resection and affects PARP inhibition. *Guotai Xu1. *, J. Ross Chapman2. n1*, Inger ...
Histone H2A phosphorylation in DNA double-strand break repair.. Foster ER1, Downs JA. ... DNA repair must take place within the context of chromatin, and it is therefore not surprising that many aspects of both ... This modification is an early response to the induction of DNA damage, and occurs in a wide range of eukaryotic organisms, ... One of the best-characterized chromatin modification events in DNA-damage responses is the phosphorylation of the SQ motif ...
Biotinylated tags bind double-strand breaks in genomic DNA; after enrichment and sequencing, this allows precise, genome-wide ... Mapping of meiotic single-stranded DNA reveals double-stranded-break hotspots near centromeres and telomeres. . Curr. Biol. 17 ... Nucleotide-resolution DNA double-strand break mapping by next-generation sequencing. *Nicola Crosetto1, 2. n11, n12*, Abhishek ... High-resolution profiling of γH2AX around DNA double strand breaks in the mammalian genome. . EMBO J. 29, 1446-1457 (2010). ...
... linear double-stranded DNA; ss, single-stranded DNA. The ratios of relaxed circular and linear double-strand DNA (rc/lin) were ... b) A double-strand break formed by I-SceI endonuclease activity. (c) Product formed by NHEJ of a double-strand break. Precise ... Double-strand breaks can be repaired by homology- and nonhomology-dependent mechanisms, although repair of double-strand breaks ... often through conversion of single-strand lesions into double-strand breaks during DNA replication in growing cells. Double- ...
DNA double-strand break repair Rad50 ATPase, putative (B0EMR2) Accession. B0EMR2 (B0EMR2_ENTDS) ...
Here we show that in Arabidopsis, endoreduplication is induced by DNA double-strand breaks (DSBs), but not directly by DNA ... Programmed induction of endoreduplication by DNA double-strand breaks in Arabidopsis. Sumiko Adachi, Kazunori Minamisawa, Yoko ... Programmed induction of endoreduplication by DNA double-strand breaks in Arabidopsis. Sumiko Adachi, Kazunori Minamisawa, Yoko ... Programmed induction of endoreduplication by DNA double-strand breaks in Arabidopsis Message Subject (Your Name) has sent you a ...
When a double-strand DNA break occurs at the target site, it is repaired through single-strand annealing between the duplicated ... Targeting DNA Double-Strand Breaks with TAL Effector Nucleases Message Subject (Your Name) has forwarded a page to you from ... Targeting DNA Double-Strand Breaks with TAL Effector Nucleases. Michelle Christian, Tomas Cermak, Erin L. Doyle, Clarice ... Targeting DNA Double-Strand Breaks with TAL Effector Nucleases. Michelle Christian, Tomas Cermak, Erin L. Doyle, Clarice ...
DNA synthesis errors associated with double-strand-break repair. Message Subject (Your Name) has forwarded a page to you from ... DNA synthesis errors associated with double-strand-break repair.. J N Strathern, B K Shafer and C B McGill ... DNA synthesis errors associated with double-strand-break repair.. J N Strathern, B K Shafer and C B McGill ... DNA synthesis errors associated with double-strand-break repair.. J N Strathern, B K Shafer and C B McGill ...
DNA Double-Strand Breaks and γ-H2AX Signaling in the Testis. Geert Hamer, Hermien L. Roepers-Gajadien, Annemarie van Duyn- ... Within minutes of the induction of DNA double-strand breaks in somatic cells, histone H2AX becomes phosphorylated at serine 139 ... "DNA Double-Strand Breaks and γ-H2AX Signaling in the Testis," Biology of Reproduction, 68(2), 628-634, (1 February 2003) ... "DNA Double-Strand Breaks and γ-H2AX Signaling in the Testis," Biology of Reproduction 68(2), 628-634, (1 February 2003). https ...
... double-strand breaks (DSBs) are one of the most harmful lesions to a cell. Failure in DSB repair could lead to genomic ... DNA double-strand break repair inhibitors as cancer therapeutics Chem Biol. 2015 Jan 22;22(1):17-29. doi: 10.1016/j.chembiol. ... Among DNA damages, double-strand breaks (DSBs) are one of the most harmful lesions to a cell. Failure in DSB repair could lead ... Besides, therapeutic agents introduce breaks in the genome as an intermediate. Therefore, blocking the residual repair using ...
Scientists have revealed an important mechanism in the repair of DNA double-strand breaks, according to new research published ... Research reveals important mechanism in the repair of DNA double-strand breaks. *Download PDF Copy ... Scientists have revealed an important mechanism in the repair of DNA double-strand breaks, according to new research published ... This repairs a severe form of DNA damage where both strands of DNA are broken. A protein called Rad51 orchestrates HR, and ...
A particularly hazardous type of DNA lesion is the double-strand break (DSB),... ... Genomic integrity is constantly challenged by DNA lesions, several thousands of which occur in each human cell every day. ... A particularly hazardous type of DNA lesion is the double-strand break (DSB), which can lead to large genetic alterations if ... Sarangi P., Zhao X. (2014) Roles of Post-translational Modifications in DNA Double-Strand Break Repair. In: Bell E. (eds) ...
At a DNA double-strand break (DSB), potentially lost sequence information cannot be recovered from the same DNA molecule. ... However, simple repair by joining two broken ends, though inherently error prone, is preferabl … ... Breaks in both DNA strands are a particularly dangerous threat to genome stability. ... Breaks in both DNA strands are a particularly dangerous threat to genome stability. At a DNA double-strand break (DSB), ...
Among the large spectrum of DNA damage induced by radiation, DNA double-strand breaks (DSBs) are considered, to date, as the ... Intrinsic radiosensitivity and DNA double-strand breaks in human cells Bibliographie. Journal title : Cancer Radiothérapie. ... Keywords > DNA double-strand breaks, DNA repair, radiosensitivity Research Unit > IRSN Authors > FORAY Nicolas, JOUBERT Aurélie ...
"Ku protein stimulates DNA end joining by mammalian DNA ligases: a direct role for Ku in repair of DNA double-strand breaks," ... DNA double-strand breaks are extremely toxic DNA lesions that arise from a variety of sources, including ionizing radiation [1 ... phosphoglycolate-terminated DNA double-strand breaks," DNA Repair, vol. 8, no. 8, pp. 901-911, 2009. View at Publisher · View ... overhangs of DNA double strand breaks by the human tyrosyl-DNA phosphodiesterase hTdp1," Journal of Biological Chemistry, vol. ...
The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem. 2010;79:181-211 ... Many pathogenic bacteria have been shown to cause host cell DNA damage, often resulting in DNA double-strand breaks (DSBs) (9, ... Aparicio T, Baer R, Gautier J. DNA double-strand break repair pathway choice and cancer. DNA Repair (Amst). 2014;19:169-175. ... PARP activation regulates the RNA-binding protein NONO in the DNA damage response to DNA double-strand breaks. Nucleic Acids ...
"Ku protein stimulates DNA end joining by mammalian DNA ligases: a direct role for Ku in repair of DNA double-strand breaks," ... phosphoglycolate-terminated DNA double-strand breaks," DNA Repair, vol. 8, no. 8, pp. 901-911, 2009. View at Publisher · View ... overhangs of DNA double strand breaks by the human tyrosyl-DNA phosphodiesterase hTdp1," Journal of Biological Chemistry, vol. ... "DNA double-strand breaks and ATM activation by transcription-blocking DNA lesions," Cell Cycle, vol. 9, no. 2, pp. 274-278, ...
Double-strand breaks (DSBs) are the most deleterious form of DNA damage induced by ionizing radiation, and the cells capacity ... 63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; BRAIN; DNA; DNA ... Journal Article: DNA Double-Strand Break Rejoining in Complex Normal Tissues. *Citation Details ...
Radiation-induced DNA double-strand breaks after myocardial scintigraphy.. Outcome Description:. DNA double-strand breaks will ... DNA Double-strand Breaks Following Myocardial Scintigraphy. Trial Phase:. N/A. Minimum Age:. 19 Years. Maximum Age:. N/A ... DNA Double-strand Breaks Following Myocardial Scintigraphy. Inclusion Criteria:. - myocardial SPECT clinically indicated. ...
A paradigm for DNA repair targeted therapy has emerged in cancers that exhibit mutations in BRCA1 or BRCA2 tumor suppressor ... A paradigm for DNA repair targeted therapy has emerged in cancers that exhibit mutations in BRCA1 or BRCA2 tumor suppressor ... cancer cells have a higher DSB burden due to oncogene-induced replication stress and acquired defects in DNA damage response ( ... cancer cells have a higher DSB burden due to oncogene-induced replication stress and acquired defects in DNA damage response ( ...
Single strand annealing (SSA) is a process that is initiated when a double strand break is made between two repeated sequences ... Purified Rad59 possesses DNA binding properties and strand annealing activity.. RPA. Another DNA binding factor, the RPA ... Single stranded regions are created adjacent to the break that extend to the repeated sequences such that the complementary ... on these observations we proposed that Msh2 and Msh3 bind to the branched junction between the single and double stranded DNA. ...
... doublestrand breaks,which are caused by many factors such as chemical treatments, radiations and, often, biological factors, ... are lethal events in organisms carrying DNA as their genome, which include bacteria ... Multiple routes in the processing of DNA doublestrand breaks in E. coli. . A doublestrand break (a-b) may be rejoined by DNA ... Repair of a DNA doublestrand break by illegitimate recombination involving short repeats. DNA doublestrand break occurs ...
... a molecules eye view of the human cells DNA repair kit as it assembled on a double-strand break to link together the broken ... Double-strand breaks are ruptures that cut completely across the twisted, ladder-like structure of DNA, breaking it into two ... High-precision technique stores cellular memory in DNA Citation: DNA repair proteins monitored at double-strand break (2007, ... DNA repair proteins monitored at double-strand break. Investigators at St. Jude Childrens Research Hospital had a molecules ...
... of a double strand DNA break (DSB) is a key step to channel the repair of the lesion towards the homologous recombination, at ... degrade DNA strand in both the directions, creating the 3′ssDNA filament. Multiple levels of regulation of the break processing ... degrade DNA strand in both the directions, creating the 3′ssDNA filament. Multiple levels of regulation of the break processing ... single strand (ss) DNA, which is covered by RPA and recombination factors. Molecular details of the process have been first ...
Contact with E. coli expressing this gene cluster causes DNA double-strand breaks and activation of the DNA damage checkpoint ... Escherichia coli Induces DNA Double-Strand Breaks in Eukaryotic Cells Message Subject. (Your Name) has forwarded a page to you ... Escherichia coli Induces DNA Double-Strand Breaks in Eukaryotic Cells. By Jean-Philippe Nougayrède, Stefan Homburg, Frédéric ... Escherichia coli Induces DNA Double-Strand Breaks in Eukaryotic Cells. By Jean-Philippe Nougayrède, Stefan Homburg, Frédéric ...
In DNA double-strand break (DSB) repair, the well-known mark of histones is the phosphorylation of the H2A variant, H2AX, which ... The ubiquitylation of histone H2B by RNF20 E3 ligase was recently found to be a DNA damage-induced histone modification. This ... of histone modifications with chromatin remodeling factors has broadened our understanding of chromatin dynamics in DNA ... DNA double-strand break repair; ubiquitylation of histone H2B; RNF20; chromatin relaxation; SNF2H; KAP-1; CHD3.1 DNA double- ...
DNA Double-Strand Breaks Trigger Genome-Wide Sister-Chromatid Cohesion Through Eco1 (Ctf7) ... DNA Double-Strand Breaks Trigger Genome-Wide Sister-Chromatid Cohesion Through Eco1 (Ctf7) ... DNA Double-Strand Breaks Trigger Genome-Wide Sister-Chromatid Cohesion Through Eco1 (Ctf7) ... DNA Double-Strand Breaks Trigger Genome-Wide Sister-Chromatid Cohesion Through Eco1 (Ctf7) ...
Upon DNA double-strand breaks (DSBs), deacetylation of H3K56 and H4K16 by HDACs occurs immediately... ... Genome stability DNA damage Histone deacetylation Histone deacetylases (HDACs) DNA repair DNA double-strand breaks (DSBs) ... Upon DNA double-strand breaks (DSBs), deacetylation of H3K56 and H4K16 by HDACs occurs immediately at break sites, and is ... Burma S, Chen BP, Murphy M, Kurimasa A, Chen DJ (2001) ATM phosphorylates histone H2AX in response to DNA double-strand breaks ...
Antibodies for proteins involved in meiotic DNA double-strand break processing pathways, according to their Panther/Gene ... Antibodies for proteins involved in meiotic DNA double-strand break processing pathways; according to their Panther/Gene ...
  • Error-free repair of DNA double-strand breaks (DSBs) is achieved by homologous recombination (HR), and BRCA1 is an important factor for this repair pathway 1 . (nature.com)
  • REV7 is recruited to DSBs in a manner dependent on the H2AX-MDC1-RNF8-RNF168-53BP1 chromatin pathway, and seems to block HR and promote end joining in addition to its regulatory role in DNA damage tolerance 6 . (nature.com)
  • We present a genome-wide approach to map DNA double-strand breaks (DSBs) at nucleotide resolution by a method we termed BLESS (direct in situ breaks labeling, enrichment on streptavidin and next-generation sequencing). (nature.com)
  • Here we show that in Arabidopsis, endoreduplication is induced by DNA double-strand breaks (DSBs), but not directly by DNA replication stress. (pnas.org)
  • ATM specifically responds to DNA double-strand breaks (DSBs), and ATR primarily senses replication stress caused by a persistent block of replication fork progression. (pnas.org)
  • To determine whether the DNA synthesis associated with repair of DSBs has a higher error rate than that associated with genome duplication, HO-induced DSBs were generated 0.3 kb from revertible alleles of trp1. (genetics.org)
  • Among DNA damages, double-strand breaks (DSBs) are one of the most harmful lesions to a cell. (nih.gov)
  • Among the large spectrum of DNA damage induced by radiation, DNA double-strand breaks (DSBs) are considered, to date, as the key-lesions responsible for the cell killing. (irsn.fr)
  • Most DNA double-strand breaks (DSBs) formed in a natural environment have chemical modifications at or near the ends that preclude direct religation and require removal or other processing so that rejoining can proceed. (hindawi.com)
  • Free radical-mediated DSBs typically bear unligatable 3′-phosphate or 3′-phosphoglycolate termini and often have oxidized bases and/or abasic sites near the break. (hindawi.com)
  • DSBs induced by ionizing radiation stem from attack by free radicals, primarily the hydroxyl radical, on deoxyribose, with formation of carbon-centered free radicals on any of the five deoxyribose carbons potentially leading to strand cleavage. (hindawi.com)
  • Double-strand breaks (DSBs) are the most deleterious form of DNA damage induced by ionizing radiation, and the cells' capacity to rejoin radiation-induced DSBs is known to affect their intrinsic radiosensitivity. (osti.gov)
  • DNA double-strand breaks (DSBs) are highly deleterious, with a single unrepaired DSB being sufficient to trigger cell death. (frontiersin.org)
  • DNA double-strand breaks (DSBs) are considered the most lethal of all DNA lesions, eliciting the majority of the cytotoxic effects induced by ionizing radiation (IR) and certain anti-cancer drugs. (frontiersin.org)
  • Two-ended DSBs are preferably repaired by two major competing pathways: classical non-homologous end joining (c-NHEJ) and homologous recombination (HR). In addition, DSBs can be subjected to alternative end joining [a-EJ, also referred to as DNA polymerase theta-mediated end joining (TMEJ)] or single-strand annealing (SSA). (frontiersin.org)
  • DSBs are classically defined as broken chromosomes, however uncapped telomere ends and reversed forks are bound and processed by the same factors. (frontiersin.org)
  • In this review we generally focus on broken chromosomes, although proteins, and mechanisms that we mention are active on whole types of DSBs. (frontiersin.org)
  • In DNA double-strand break (DSB) repair, the well-known mark of histones is the phosphorylation of the H2A variant, H2AX, which has been used as a surrogate marker of DSBs. (mdpi.com)
  • Faithful chromosome segregation and repair of DNA double-strand breaks (DSBs) require cohesin, the protein complex that mediates sister-chromatid cohesion. (sciencemag.org)
  • Using budding yeast, we challenge this model by showing that cohesion is generated by an Eco1-dependent but replication-independent mechanism in response to DSBs in G 2 /M. Furthermore, our studies reveal that Eco1 has two functions: a cohesive activity and a conserved acetyltransferase activity, which triggers the generation of cohesion in response to the DSB and the DNA damage checkpoint. (sciencemag.org)
  • Cohesion plays a crucial role in chromosome segregation ( 1 ) as well as post-replicative repair of double-strand breaks (DSBs) ( 2 ) and is mediated by a large ring-shaped complex, cohesin, and its associated protein, Pds5 ( 3 , 4 ). (sciencemag.org)
  • However, cohesion is generated in G 2 /M upon irradiation ( 9 ) and was inferred to be mediated by cohesin loaded de novo around DSBs by a mechanism dependent on the DNA damage checkpoint ( 9 , 11 , 12 ). (sciencemag.org)
  • To determine whether DNA replication is required for DSB-induced cohesion, we developed an assay to detect cohesion of specific regions on chromosomes in response to defined DSBs ( Fig. 1A ). (sciencemag.org)
  • Upon DNA double-strand breaks (DSBs), deacetylation of H3K56 and H4K16 by HDACs occurs immediately at break sites, and is crucial for DSB repair. (springer.com)
  • Here we describe two assays that examine defective DSB repair caused by HDAC inhibition in primary cortical neurons: single-cell gel electrophoresis to assay DNA integrity (the comet assay) and western blot analysis for γH2AX, a phosphorylated histone variant associated with DSBs. (springer.com)
  • These data demonstrate a critical role for Dicer in promoting survival of thymocytes experiencing DNA double-strand breaks (DSBs) during TCRβ recombination. (jimmunol.org)
  • This paper introduces the Multicellular Signalling (MULTISIG1) model in which DNA double-strand break (DSB) repair initiation requires intercellular stress-response signalling from a threshold number of cells with DSBs, which occurs at the threshold radiation absorbed dose, T. The model applies to low radiation doses and employs an exponential distribution of times to DNA DSB repair completion with mean β. (environmental-expert.com)
  • The purpose of present study is to evaluate the induction of clastogenic effect after chronic exposure to low dose of ionising radiation in both CHO-K1 cells and in their DNA Double-Strand Breaks (DSBs)-repair deficient mutant xrs-5. (environmental-expert.com)
  • Unrepaired and misrepaired DNA Double-Strand Breaks (DSBs) were shown to be the key events of radiation-induced toxicity (radiosensitivity) and genomic instability (cancer proneness), respectively. (environmental-expert.com)
  • Depletion of polyamines sensitizes cells to DNA damage agents that lead to DNA double-strand breaks (DSBs), suggesting that endogenous polyamines may participate in DNA repair process. (aacrjournals.org)
  • DNA double-strand breaks (DSBs) jeopardize genome integrity and can-when repaired unfaithfully-give rise to structural rearrangements associated with cancer. (mdpi.com)
  • Exogenous agents such as ionizing radiation or chemotherapy can invoke DSBs, but a vast amount of breakage arises during vital endogenous DNA transactions, such as replication and transcription. (mdpi.com)
  • Genomic integrity is threatened by cytotoxic DNA double-strand breaks (DSBs), which must be resolved efficiently to prevent sequence loss, chromosomal rearrangements/translocations, or cell death. (rcsb.org)
  • The DNA-dependent protein kinase catalytic subunit (DNA-PK CS ) plays an important role during the repair of DNA double-strand breaks (DSBs). (rupress.org)
  • To study DNA-PK CS recruitment in vivo, we used a laser system to introduce DSBs in a specified region of the cell nucleus. (rupress.org)
  • However, impairment of both of these functions results in deficient DSB repair and the maintained presence of DNA-PK CS at unrepaired DSBs. (rupress.org)
  • DNA double-strand breaks (DSBs) are especially genotoxic DNA lesions because they potentially lead to chromosomal breakage, fragmentation, and translocation. (rupress.org)
  • DNA double-strand breaks (DSBs) and their repair can cause extensive epigenetic changes. (harvard.edu)
  • Using this model, we show that DSBs promote a DNA damage signaling-dependent decrease in gene expression in primary cells specifically at break-bearing genes, which is reversed upon DSB repair. (harvard.edu)
  • Together, our findings reveal an unexpected capacity of primary cells to maintain transcriptome integrity in response to DSBs, pointing to a limited role for DNA damage as a mediator of cell-autonomous epigenetic dysfunction. (harvard.edu)
  • Two major pathways for repairing DNA double-strand breaks (DSBs) have been identified in mammalian cells, nonhomologous end-joining (NHEJ) and homologous recombination (HR). Inactivation of NHEJ is known to lead to an elevated level of spontaneous and radiation-induced chromosomal rearrangements associated with an increased risk of tumorigenesis. (aacrjournals.org)
  • We propose that it serves as an efficient pathway for rejoining correct break ends in situations of separated breaks but generates genomic rearrangements if DSBs are close in time and space. (aacrjournals.org)
  • Of the many types of DNA damage, DNA double-strand breaks (DSBs) represent a particularly dangerous form of damage. (asm.org)
  • DSBs can arise spontaneously or may be induced by exogenous DNA damaging agents. (asm.org)
  • Maintaining genome integrity through the repair of DNA double-strand breaks (DSBs) is critical to cell survival. (asm.org)
  • Multiple pathways for repairing DNA DSBs have been identified, including synthesis-dependent strand annealing both with and without extended DNA synthesis ( 31 , 45 ), nonhomologous end joining, and homologous recombination (HR), working in a coordinated manner on the various damage types ( 36 , 37 ). (asm.org)
  • The process of HR repair of DNA DSBs in both the Bacteria and Eukarya has been extensively studied (see reviews in references 24 , 25 , 38 , 41 , and 44 ). (asm.org)
  • Rad50 has an ATP-dependent DNA binding activity, and coiled-coil domains of Rad50 are separated by a zinc hook found to be required for the repair of DSBs by HR ( 43 ). (asm.org)
  • Deletions of sbcC and/or sbcD in D. radiodurans also result in delayed repair kinetics of DNA DSBs following γ irradiation ( 5 ). (asm.org)
  • DNA double-strand breaks (DSBs) are considered the most biologically damaging lesions produced by ionizing radiation (IR) and some chemicals. (asm.org)
  • Higher eukaryotic cells primarily repair DSBs by one of two genetically separable pathways, nonhomologous end joining (NHEJ) and homologous recombination (HR). NHEJ repairs broken ends with little or no requirement for sequence homology and involves the XRCC4-LIG4 complex and the DNA-dependent protein kinase (DNA-PK) holoenzyme, consisting of the DNA end-binding heterodimer Ku70-Ku80 and the catalytic subunit DNA-PK cs ( 22 , 23 , 53 ). (asm.org)
  • However, when IR produce double-strand breaks (DSBs) in DNA it comes a large rise in relative biological response to cellular damage. (wikipathways.org)
  • In general terms, IRs produce a wide variety of DNA lesions and DSBs are considered to be the major actor responsible for cell death. (wikipathways.org)
  • The production of DSBs can be quantified by biochemical techniques, e.g., pulsed field gel electrophoresis (PFGE) and cell imaging, either globally or damage specific, through immunostaining of marker proteins or recruitment of fluorescent proteins to the DNA breaks. (wikipathways.org)
  • A major role is that of the MRN (MRE11/RAD50/NBS1) complex binding to DSBs and facilitating the activation of ATM (Ataxia Telangiectasia Mutated) protein, a key PI3K (Phosphatidylinositol 3-kinase) related kinase in the DNA damage response (DDR). (wikipathways.org)
  • We analysed protein-DNA and protein-protein interactions relevant to the repair of DNA DSBs (double-strand breaks) by NHEJ (non-homologous end-joining). (portlandpress.com)
  • Consequently, cells expressing the DNA binding mutant CtIP are defective in DSB resection and HR. Collectively, our work highlights minimal structural requirements for CtIP protein family members to facilitate the processing of DSBs, thereby maintaining genome stability as well as enabling sexual reproduction. (bioportfolio.com)
  • In this article, we focused on the detection of DNA double-strand breaks (DSBs) by phosphorylated histone H2AX (known as gammaH2AX) and p53-binding protein 1 (53BP1) in three distinct lines of hiPSCs, their source cells, and one line of human embryonic stem cells (hESCs). (muni.cz)
  • To assess the variations in the functionality of the DNA repair system among the samples, the number of DSBs induced by gamma-irradiation and the decrease over time was analysed. (muni.cz)
  • In this study, we show that SETD2, the enzyme that trimethylates histone H3 lysine 36 (H3K36me3), is required for ATM activation upon DNA double-strand breaks (DSBs). (elifesciences.org)
  • DNA double-strand breaks (DSBs) are the most catastrophic form of DNA damage and pose great threat to genome stability. (elifesciences.org)
  • The major sensor of DSBs is ataxia telangiectasia mutated (ATM) kinase, which is critical for the initial steps of the DNA damage response (DDR). (elifesciences.org)
  • DNA double-strand breaks (DSBs) are a highly mutagenic form of DNA damage that can be repaired through one of several pathways with varied degrees of sequence preservation. (prolekare.cz)
  • DNA double-strand breaks (DSBs) are the most dangerous type of DNA damage due to their tendency to lead to chromosomal rearrangements, a hallmark of tumorigenesis, when they are repaired [ 1 ]. (prolekare.cz)
  • Bacillus subtilis cells respond to double strand breaks (DSBs) with an ordered recruitment of repair proteins to the site lesion, being RecN one of the first responders. (csic.es)
  • End-processing activities and the RecA protein itself contribute to increase RecN levels after DNA DSBs. (csic.es)
  • DNA double-strand breaks (DSBs) constitute a particularly toxic type of DNA lesion. (theses.cz)
  • The proper repair of DSBs is critical for cell well-being, as unrepaired breaks can cause cell death or genome rearrangements that can lead to cancer. (theses.cz)
  • The role of ATM as a key regulator of signaling following DNA double-strand breaks (DSBs) has been dissected in extraordinary detail, but the impact of this process on DSB repair still remains controversial. (sebbm.es)
  • Homologous recombination (HR) repairs DNA double-strand breaks (DSBs) to maintain genomic integrity. (physiciansweekly.com)
  • We map the MEILB2-binding domain within BRCA2 that is distinct from the canonical DNA-binding domain but is sufficient to localize to meiotic DSBs in a MEILB2-dependent manner. (physiciansweekly.com)
  • Efficient and correct repair of DNA damage, especially DNA double-strand breaks (DSBs), is vital for the survival of individual cells and organisms. (diva-portal.org)
  • The lesions transformed to DSBs during incubation at 50ºC were repaired within 60-90 minutes in vivo and the repair was independent of DNA-PK, XRCC1 and PARP-1. (diva-portal.org)
  • We show that DSBs are processed into long single-stranded DNA (ssDNA) ends after ≥1 h of repair in NHEJ deficient cells. (diva-portal.org)
  • Persistent DNA double-strand breaks (DSBs) are recruited to the nuclear periphery in budding yeast. (uzh.ch)
  • Previous results showed that some polymorphic changes in LIG4 impact on the efficiency of double strand breaks (DSBs) repair. (bham.ac.uk)
  • Abstract: DNA double-strand breaks (DSBs) are repaired by homology-directed repair or non-homologous end joining. (tufts.edu)
  • This action seems to be related to suppression of cellular DNA DSB repair activities because NHEJ-mediated rejoining of DSBs occurs with significantly lower efficiency in the presence of trifluoperazine. (diva-portal.org)
  • Rassool, F.V. Genomic instability in myeloid malignancies: Increased Reactive Oxygen Species (ROS), DNA Double Strand Breaks (DSBs) and error-prone repair. (eurekaselect.com)
  • Here, we provide genetic and biochemical evidence that DNA double‐strand breaks (DSBs) can be directly generated by Top1 at sites of genomic ribonucleotides. (embopress.org)
  • We demonstrate biochemically that irreversible DSBs are generated by subsequent Top1 cleavage on the opposite strand from the Top1‐induced DNA nicks at ribonucleotide sites. (embopress.org)
  • Sequential Top1 cleavage on the opposite strand can directly lead to DNA double‐strand breaks (DSBs), causing replication stress and genome instability and requiring repair by homologous recombination. (embopress.org)
  • Ionizing radiation (IR) induces a variety of DNA lesions among which DNA double strand breaks (DSBs) are biologically most significant. (tu-darmstadt.de)
  • In parallel to this event, DNA repair machinery repairs the DSBs. (tu-darmstadt.de)
  • The majority of IR-induced DSBs are repaired fast via canonical non-homologous end-joining (c-NHEJ) in which DNA-PKcs is one of the core enzymes. (tu-darmstadt.de)
  • The expression of ERGs depends on NMDAR-induced DNA-double strand breaks (DSBs) in the transcriptional start site of these genes. (tu-darmstadt.de)
  • Comet assay analysis of isolated nuclei showed atlig1 - RNAi lines displayed slower repair of single strand breaks (SSBs) and also double strand breaks (DSBs), implicating AtLIG1 in repair of both these lesions. (biomedcentral.com)
  • Little information is available on the ability of terminally differentiated cells to efficiently repair DNA double strand breaks (DSBs), and one might reasonably speculate that efficient DNA repair of these threatening DNA lesions, is needed in cells of long life span with no or limited regeneration from precursor. (inserm.fr)
  • Few tissues are available besides neurons that allow the study of DNA DSBs repair activity in very long-lived cells. (inserm.fr)
  • In mammalian cells, DSBs are mainly repaired by the non-homologous end-joining pathway (NHEJ) that relies on the DNA dependent protein kinase (DNA-PK) activity. (inserm.fr)
  • The increased in DNA DSBs repair activity observed in adipocytes was due to the increase in DNA-PK activity as shown by the use of DNA-PK inhibitor or sub-clones of 3T3F442A deficient in DNA-PKcs using long term RNA interference. (inserm.fr)
  • Finally, similar positive regulation of DNA-PKcs expression and activity was observed during differentiation of primary culture of pre-adipocytes isolated from human sub-cutaneous adipose tissue.Our results show that DNA DSBs repair activity is up regulated during the early commitment into adipogenesis due to an up-regulation of DNA-PK expression and activity. (inserm.fr)
  • In opposition to the general view that DNA DSBs repair is decreased during differentiation, our results demonstrate that an up-regulation of this process might be observed in post-mitotic long-lived cells. (inserm.fr)
  • DNA double-strand breaks (DSBs) are deleterious lesions that are generated in response to ionizing radiation or replication fork collapse that can lead to genomic instability and cancer. (preprints.org)
  • Of particular importance are the repair pathways, which respond to DNA double-strand breaks (DSBs), and how the efficiency of repair is influenced by sequence homology. (elsevier.com)
  • The rapid cellular responses to DSBs may be blocked by compact heterochromatin structure which then allows these breaks to be repaired by a more precise ATM-dependent pathway. (biomedcentral.com)
  • Interestingly, these DNA lesions, which are the product of recombination between different loci, are mediated by DNA double strand breaks (DSBs). (biomedcentral.com)
  • Synthesis-dependent strand annealing (SDSA) is a major mechanism of homology-directed repair of DNA double-strand breaks (DSBs). (wikipedia.org)
  • Now, interactions between both double-stranded break-repair pathways and other cellular processes, such as cell-cycle regulation and replication, are being unveiled. (nih.gov)
  • When replication of an avian hepadnavirus, duck hepatitis B virus, occurred at the time of double-strand break repair, we observed integration of viral DNA at the site of the break with a frequency of ≈10 -4 per transfected cell. (pnas.org)
  • Spontaneous integration of viral DNA into host chromosomes occurs in both chronic and acute infections, but in contrast to retroviruses, viral integration does not play a role in hepadnavirus replication ( 4 - 8 ). (pnas.org)
  • Replication of duck HBV (DHBV) in the cells undergoing imprecise repair of the induced double-strand break resulted in integration of viral DNA at the repaired site 7-14% of the time. (pnas.org)
  • Genome integrity is continuously threatened by external stresses and endogenous hazards such as DNA replication errors and reactive oxygen species. (pnas.org)
  • Eukaryotic DNA damage checkpoints delay or arrest the cell cycle to provide time for DNA repair before the cell enters a new round of DNA replication or mitosis ( 1 ). (pnas.org)
  • Compared to healthy cells, cancer cells have a higher DSB burden due to oncogene-induced replication stress and acquired defects in DNA damage response (DDR) mechanisms. (frontiersin.org)
  • While healthy cells have to deal with a minor amount of damage and take advantage of the full DNA repair capacity, malignant cells are frequently equipped with reduced DNA repair functionality to cope with increased replication stress and elevated levels of endogenous DNA damage ( 3 ). (frontiersin.org)
  • An allele of RPA1 , rpa1-t11 , is partially defective for SSA but is still capable of carrying out its role in DNA replication as cells appear to grow normally. (brandeis.edu)
  • Cohesion between sister chromatids is thought to be generated only during ongoing DNA replication by an obligate coupling between cohesion establishment factors such as Eco1 (Ctf7) and the replisome. (sciencemag.org)
  • Many anticancer chemotherapeutic agents inhibit DNA metabolism by targeting DNA replication process. (aacrjournals.org)
  • The cellular methyl donor S-adenosylmethionine (SAM) and other endo/exogenous agents methylate DNA bases non-enzymatically into products interfering with replication and transcription. (medworm.com)
  • SbcCD has been shown to cleave hairpin DNA, which can block stalled replication forks, prior to homologous recombination rescue of the fork ( 8 ). (asm.org)
  • They also arise endogenously during DNA replication or as initiators of programmed processes, such as V(D)J recombination and meiotic exchange. (asm.org)
  • The accurate preservation of chromosome continuity in human cells during either DNA replication or repair is critical for preventing the conversion of normal cells to an oncogenic status. (wikipathways.org)
  • We have previously shown that Escherichia coli cells subject to a single, repairable site-specific DNA double-strand break (DSB) per DNA replication cycle reach a new average cell length, with a negligible effect on population growth rate. (prolekare.cz)
  • This delay occurs despite unperturbed cell size regulated initiation of both chromosomal DNA replication and cell division. (prolekare.cz)
  • Furthermore, despite DSB repair altering the profile of DNA replication across the genome, the time required to complete chromosomal duplication is invariant. (prolekare.cz)
  • Broken replication forks trigger heritable DNA breaks in the terminus of a circular chromosome. (prolekare.cz)
  • Relationship between cell size and time of initiation of DNA replication. (prolekare.cz)
  • 7. Wold S, Skarstad K, Steen HB, Stokke T, Boye E. The initiation mass for DNA replication in Escherichia coli K-12 is dependent on growth rate. (prolekare.cz)
  • The MMR pathway acts to remove bases that are mispaired as a result of a failure during replication, illustrated by the functional interaction of the MMR proteins with the DNA replication factor PCNA ( 5 , 8 ). (asm.org)
  • DNA ligase enzymes catalyse the joining of adjacent polynucleotides and as such play important roles in DNA replication and repair pathways. (biomedcentral.com)
  • DNA ligase 1, present in all eukaryotes, plays critical roles in both DNA repair and replication and is indispensable for cell viability. (biomedcentral.com)
  • Reduced levels of Arabidopsis DNA ligase 1 in the silenced lines are sufficient to support plant development but result in retarded growth and reduced cell size, which may reflect roles for AtLIG1 in both replication and repair. (biomedcentral.com)
  • These results indicate that DNA ligase 1 functions in both DNA replication and in repair of both ss and dsDNA strand breaks in higher plants. (biomedcentral.com)
  • These enzymes seal gaps in the sugar-phosphate backbone of DNA that arise during DNA replication, DNA damage and repair. (biomedcentral.com)
  • Eukaryotes have evolved multiple DNA ligase isoforms, with both specific and overlapping roles in the replication and repair of the nuclear and organellar genomes. (biomedcentral.com)
  • DNA ligase 1 (LIG1) is present in all eukaryotes where it is required for joining DNA fragments produced during DNA replication. (biomedcentral.com)
  • Various viruses have evolved a plethora of strategies to manipulate DNA damage machinery and commandeer cells to maximize their own replication. (pirbright.ac.uk)
  • Most studies have focused on the relationship between DNA virus replication and the host DDR pathway, but few have investigated the interface between the DDR pathway and ribonucleic acid (RNA) viruses, such as oncolytic Newcastle disease virus (NDV). (pirbright.ac.uk)
  • Maintenance of genome stability is carried out by a suite of DNA repair pathways that ensure the repair of damaged DNA and faithful replication of the genome. (elsevier.com)
  • SDSA is unique in that D-loop translocation results in conservative rather than semiconservative replication, as the first extended strand is displaced from its template strand, leaving the homologous duplex intact. (wikipedia.org)
  • This dismantling activity is specific for Rad51 since Srs2 does not dismantle DMC1 (a meiosis-specific Rad51 homolog), Rad52 (a Rad 51 mediator) or replication protein A (RPA, a single-stranded DNA binding protein). (wikipedia.org)
  • During the process, all cell duplication process, including mitosis, meiosis as well as DNA replication, will be paused. (wikipedia.org)
  • The permanent cell cycle withdrawal is mainly done by the wearing off of DNA sequences during S Phase, the second stage during a DNA replication progress. (wikipedia.org)
  • During the replication process, the DNA replication enzymes are not able to copy the ending sequences at the telomere. (wikipedia.org)
  • It replenishes the telomeres that are lost during DNA replication, compensating for enough telomerase sequence so that the useful DNA content would not be damaged. (wikipedia.org)
  • Chromosomal stability and the DNA double-stranded break connection. (nih.gov)
  • Double-stranded breaks in DNA are important threats to genome integrity because they can result in chromosomal aberrations that can affect, simultaneously, many genes, and lead to cell malfunctioning and cell death. (nih.gov)
  • TDP1 facilitates chromosomal single-strand break repair in neurons and is neuroprotective in vivo," EMBO Journal , vol. 26, no. 22, pp. 4720-4731, 2007. (hindawi.com)
  • Bacterial cells dying from chromosomal DNA double‐strand breaks made by a restriction enzyme. (els.net)
  • David LeachSeries Type : OtherOrganism : Escherichia coli K-12The effect of a site-specific DNA double-strand break on the abundance of E. coli chromosomal DNA during exponential growth was investigated by marker frequency analysis (MFA). (medworm.com)
  • This shows that in situations of separated breaks, NHEJ deficiency leads to genomic rearrangements, in agreement with chromosomal studies. (aacrjournals.org)
  • We studied Rad51-dependent HR and random chromosomal integration of linearized plasmid DNA, a subtype of NHR, which we demonstrate to be dependent on the Mre11-Rad50-Nbs1 complex. (asm.org)
  • The data on the DSB hotspots in human ribosomal DNA gene clusters and their possible association with chromosomal translocations are presented. (springer.com)
  • TA transitions and DNA breaks leading to chromosomal rearrangements in human cancer genomes. (pasteur.fr)
  • However, very little is known about RNA-DNA HR. Previously, it was demonstrated that synthetic RNA-containing molecules can serve as templates for repairing defective or broken homologous chromosomal DNA in yeast, human and bacterial cells, but it remained unclear whether cellular RNA transcripts can recombine with genomic DNA. (gatech.edu)
  • Here, we investigated whether yeast cells can use transcript RNA as a template to repair a chromosomal DSB either directly or indirectly, if the RNA is converted first into a DNA copy, cDNA. (gatech.edu)
  • We developed a system to detect HR between chromosomal DNA and transcript RNA in budding yeast, Saccharomyces cerevisiae. (gatech.edu)
  • Here we show, that pollambda participates at the molecular level in a chromosomal context, in the repair of DNA double strand breaks (DSB) via non-homologous end joining (NHEJ) in mammalian cells. (inserm.fr)
  • The loss of chromosomal integrity from DNA double-strand breaks introduced into mammalian cells by ionizing radiation results in the specific phosphorylation of histone H2AX on serine residue 139, yielding a specific modified form named γ-H2AX. (rupress.org)
  • These results offer direct visual confirmation that γ-H2AX forms en masse at chromosomal sites of DNA double-strand breaks. (rupress.org)
  • Despite covalent blockage of the 5′ ends of both strands by protein or RNA, the ends of these molecules have been shown to undergo efficient intra- and intermolecular ligation by nonhomologous end joining (NHEJ). (pnas.org)
  • We previously suggested that integration into cellular chromosomes may occur by NHEJ at double-strand breaks in cellular DNA ( 15 , 16 ). (pnas.org)
  • We concluded that the repair of double-strand breaks by imprecise NHEJ is sometimes accompanied by insertion of viral sequences, implying that the amount of integrated viral DNA in the liver may reflect the degree of overall genetic damage sustained by the liver during a course of chronic hepatitis. (pnas.org)
  • In all the eukaryotic cells, nucleolytic processing (resection) of a double strand DNA break (DSB) is a key step to channel the repair of the lesion toward the homologous recombination, at the expenses of the non-homologous end joining (NHEJ). (frontiersin.org)
  • DNA:RNA hybrids), which interfere with their repair through NHEJ and HDR ( Figures 1A-C ). Moreover, an irreparable DSB can be eventually processed by telomerase and DNA polymerase alpha-primase (Pol α-Prim), together with other factors, leading to de novo telomere addition ( Putnam and Kolodner, 2017 ). (frontiersin.org)
  • Polymerase μ (Polμ) participates in DSB repair via the nonhomologous end-joining (NHEJ) pathway, by filling small sequence gaps in broken ends to create substrates ultimately ligatable by DNA Ligase IV. (rcsb.org)
  • These structures demonstrate that Polμ may address complementary DSB substrates during NHEJ in a manner indistinguishable from single-strand breaks. (rcsb.org)
  • It is recruited to DNA ends in the early stages of the nonhomologous end-joining (NHEJ) process, which mediates DSB repair. (rupress.org)
  • We suggest a model in which DNA-PK CS phosphorylation/autophosphorylation facilitates NHEJ by destabilizing the interaction of DNA-PK CS with the DNA ends. (rupress.org)
  • NHEJ is considered to be the prevailing pathway during the G0 and G1 phases of the cell cycle in mammalian cells because this repair pathway does not require the presence of an intact DNA template. (rupress.org)
  • NHEJ involves juxtaposition of DNA ends by an enzymatic machinery and subsequent ligation. (rupress.org)
  • Ligase IV-XRCC4 mediates ligation of the juxtaposed DNA ends in the final NHEJ step. (rupress.org)
  • To investigate, on the DNA level, the influence of a defect in NHEJ on the formation of genomic rearrangements, we applied an assay based on Southern hybridization that allows the identification and quantification of incorrectly rejoined DSB ends produced by ionizing radiation. (aacrjournals.org)
  • Our results suggest that Msh2 influences error-prone NHEJ repair at the step of pairing of terminal DNA tails. (biomedsearch.com)
  • Little is known about the quantitative contributions of nonhomologous end joining (NHEJ) and homologous recombination (HR) to DNA double-strand break (DSB) repair in different cell cycle phases after physiologically relevant doses of ionizing radiation. (asm.org)
  • HR, which appears to be less important than NHEJ for repairing IR-induced breaks in higher eukaryotes, utilizes extensive homology to faithfully restore the sequence at the break site by processes that involve proteins of the Rad52 epistasis group ( 20 , 61 , 62 , 63 ). (asm.org)
  • The protein-protein and protein-DNA interactions detected and analysed generate a framework for the characterization of molecular interactions fundamental to the function of NHEJ pathways in higher eukaryotes. (portlandpress.com)
  • During NHEJ, the broken DNA ends are blocked from 5′ end resection and held in close proximity by the Ku70-Ku80 heterodimer (Ku) ( Lieber, 2010 ). (elifesciences.org)
  • The ssDNA was formed outside of the G 1 phase of the cell cycle and only in the absence of the NHEJ proteins DNA-PK and DNA Ligase IV/XRCC4. (diva-portal.org)
  • Correlating the patterns of SD-MMEJ consistent repeats at breaks from C-NHEJ proficient and deficient backgrounds with sequence content and break end structure confirms a complex relationship among sequence content, genetic background, and end-joining repair outcome. (tufts.edu)
  • In the present study, we investigated the effect of trifluoperazine on (a) survival of bleomycin-treated human non-small cell lung carcinoma U1810 cells, (b) induction and repair of bleomycin-induced DNA strand breaks, and (c) nonhomologous end-joining (NHEJ), the major DNA double-strand break (DSB) repair pathway in mammalian cells. (diva-portal.org)
  • Our data support a requirement for pollambda in repairing a subset of DSB in genomic DNA, thereby contributing to the maintenance of genetic stability mediated by the NHEJ pathway. (inserm.fr)
  • The finding that DNA ligase 1 plays an important role in DSB repair in addition to its known function in SSB repair, demonstrates the existence of a previously uncharacterised novel pathway, independent of the conserved NHEJ. (biomedcentral.com)
  • DNA double strand breaks induced by DNA damaging agents, such ionizing radiation, are repaired by multiple DNA repair pathways including non-homologous end-joining (NHEJ) repair and homologous recombination (HR) repair. (altmetric.com)
  • Whereas the roles of protein-DNA interactions in HR and NHEJ have been fairly well defined, the functions of small and long non-coding RNAs and RNA-DNA hybrids in the DNA damage response is just beginning to be elucidated. (preprints.org)
  • The repair may occur through a few different but complementary pathways like homology directed repair (HDR), nonhomologous end joining (NHEJ), microhomology-mediated end joining (MMEJ) and single-strand annealing (SSA). (igtrcn.org)
  • These detrimental consequences are counteracted by two mechanistically distinct pathways of double-stranded break repair: homologous recombination and non-homologous end-joining. (nih.gov)
  • We argue that although categorizing different DSB repair mechanisms along pathways and subpathways can be conceptually useful, in cells flexible and reversible interactions among DSB repair factors form a web from which a nonpredetermined path to repair for any number of different DNA breaks will emerge. (nih.gov)
  • During tumorigenesis, however, precancerous cells frequently acquire loss-of-function alterations in DDR genes, including core components of selected DNA repair pathways, to accelerate mutagenesis and become malignant ( 2 ). (frontiersin.org)
  • In summary, cancer cells are often compromised in their ability to adequately process DNA damage, which exerts selective pressure to sustain DNA repair through upregulation of mutagenic pathways, ultimately promoting disease progression and therapy resistance ( 4 , 5 ). (frontiersin.org)
  • Importantly, functional interdependencies between different DNA repair pathways and within compensatory DSB repair mechanisms offer therapeutic opportunities to selectively treat DDR-deficient tumors based on the concept of synthetic lethality (SL) ( 3 , 5 , 8 , 9 ). (frontiersin.org)
  • Among the DNA repair pathways, the homologous recombination process of the DNA DSB repair seems to best fit this criterion. (aacrjournals.org)
  • However, these studies have been carried out with restriction enzyme-cut breaks, whereas only limited information is available about the mechanisms and the enzymatic pathways involved in rejoining radiation-induced breaks. (aacrjournals.org)
  • In the Bacteria , this is done primarily by the RecBCD complex, although there are redundant pathways for RecBCD activities, including the use of the RecFOR complex for recombinase loading along with the RecQ helicase and RecJ nuclease for DNA end processing ( 44 ). (asm.org)
  • Both pathways proceed through a cascade of events whereby DNA damage sensors, transducers, and effectors detect and rejoin the broken DNA ends ( Harper and Elledge, 2007 ). (elifesciences.org)
  • A number of different pathways can give rise to these Alu/Alu deletions, including single-strand annealing (SSA) repair that may predominate when there are high levels of homology, and mechanisms such as microhomology-mediated end joining (MMEJ) where the microhomology happens to be 'in register' between the two Alu elements, allowing formation of a single chimeric Alu element [ 7 ]. (prolekare.cz)
  • To determine whether these types of alterations result when DNA repair pathways are eliminated, we constructed yeast strains bearing deletions in six genes involved in mismatch repair ( MSH2 and PMS1 ) or double-strand break repair ( MRE11, RAD50, RAD52 , and YKU80 ). (asm.org)
  • The effectiveness of numerous anti-tumor therapies depends on induction of DNA damage therefore tumor cells expressing abnormalities in genes whose products are crucial for DNA repair pathways are promising targets for synthetic lethality. (eurekaselect.com)
  • Here, we discuss mechanistic aspects of synthetic lethality in the context of deficiencies in DNA double strand break repair pathways. (eurekaselect.com)
  • In somatic cells, several cellular DNA damage response (DDR) mechanisms such as cell cycle checkpoints and DSB repair pathways work in concern to handle these threats. (tu-darmstadt.de)
  • DNA ligase 1 also plays important roles in DNA single strand break (SSB) repair pathways in mammals and yeast. (biomedcentral.com)
  • ATM-dependent DNA damage checkpoint regulates a part of DNA repair pathways, however, the exact role of ATM activity remains to be elucidated. (altmetric.com)
  • Genomic integrity is constantly challenged by DNA lesions, several thousands of which occur in each human cell every day. (springer.com)
  • The MR (Mre11 nuclease and Rad50 ABC ATPase) complex is an evolutionarily conserved sensor for DNA double-strand breaks, highly genotoxic lesions linked to cancer development. (rcsb.org)
  • In addition, its enhanced capacity may allow a faster repair of spontaneous DNA lesions arisen from rapid proliferation of the cancer cells. (aacrjournals.org)
  • BRCA1-deficient cells are hypersensitive to IR and DNA cross-linking agents, and the repair of both classes of lesions involves HR ( 5 , 16 , 41 , 53 ). (asm.org)
  • However, despite the persistence of DNA lesions, SETD2-deficient cells failed to activate p53, a master guardian of the genome rarely mutated in ccRCC and showed decreased cell survival after DNA damage. (elifesciences.org)
  • A double-strand break (DSB) is one of the most deleterious DNA lesions and its repair is crucial for genome stability. (gatech.edu)
  • One of the most serious cellular lesions induced by radiation is the random DNA double-strand break. (rupress.org)
  • Chromosome breaks created by these engineered nucleases stimulate homologous recombination or gene targeting: in the presence of a template for repairing the double-strand break, specific DNA sequence changes in the template become incorporated into chromosomes at or near the break site. (genetics.org)
  • One of the main DNA repair processes is called homologous recombination (HR). This repairs a severe form of DNA damage where both strands of DNA are broken. (news-medical.net)
  • A paradigm for DNA repair targeted therapy has emerged in cancers that exhibit mutations in BRCA1 or BRCA2 tumor suppressor genes, conferring a strong defect in homologous recombination, a major and error-free DSB repair pathway. (frontiersin.org)
  • As lambdoid bacteriophage recombination function action of RecE (or Red α) exonuclease generates 3′ single‐strand tail (e), which will pair with a homologous DNA. (els.net)
  • This results in homologous recombination near the break (f). (els.net)
  • As bacterial homologous recombination DNA degradation by RecBCD exonuclease/helicase from the double‐strand break (g) is attenuated at χ sequence. (els.net)
  • Near χ, RecA promotes homolgous recombination with a homologous DNA (i). (els.net)
  • The endonuclease introduces a double‐strand break at an unoccupied, homologous site. (els.net)
  • Left) The restriction break may be repaired by homologous recombination functions carried by the bacteriophage or its resident homologous prophage. (els.net)
  • Living organisms repair DNA by a variety of mechanisms including excision repair (base excision and nucleotide excision) and DNA double-stranded break (DSB) repair (homologous recombination and nonhomologous end joining) systems ( 5 , 8 -12 ). (aacrjournals.org)
  • Cells that are deficient in homologous recombination process are less prone to mutagenesis as cells lacking the DNA excision repair or the DNA mismatch repair pathway. (aacrjournals.org)
  • A growing body of evidence suggests that promotion of DNA double-strand break repair by homologous recombination (HR) may be the means by which BRCA1 maintains genomic stability, while a role of BRCA1 in error-prone nonhomologous recombination (NHR) processes has just begun to be elucidated. (asm.org)
  • Homology-mediated repair requires an undamaged template molecule that contains a homologous DNA sequence ordinarily on a sister chromatid or a homologous chromosome. (asm.org)
  • Deletion of the recD gene drastically decreased the length of resection, allowing for recombination with short ectopic plasmid homologies and significantly increasing the efficiency of horizontal gene transfer between strains.We thus visualized and quantified DNA end resection by the RecBCD complex in live cells, recorded DNA-degradation linked to end resection and uncovered a general relationship between the length of end resection and the choice of the homologous recombination template. (tudelft.nl)
  • strain NRC-1 encodes homologs of the eukaryotic Mre11 and Rad50 proteins, which are involved in the recognition and end processing of DNA double-strand breaks in the homologous recombination repair pathway. (asm.org)
  • This is the first identification of a Rad50-independent function for the Mre11 protein, and it represents a shift in the Archaea away from the eukaryotic model of homologous recombination repair of DNA double-strand breaks. (asm.org)
  • For the purposes of this study, we will refer to any DNA repair event that occurs through either homologous or homeologous recombination between two non-allelic Alu elements and generates a single chimeric, Alu element, as Alu/Alu recombination. (prolekare.cz)
  • A meiosis-specific BRCA2 binding protein recruits recombinases to DNA double-strand breaks to ensure homologous recombination. (physiciansweekly.com)
  • End-joining repair can be classified as classical non-homologous end joining, which requires DNA ligase 4, or "alternative" end joining (alt-EJ), which does not. (tufts.edu)
  • The switch from mutagenic to error-free DNA double strand break repair by homologous recombination is therefore controlled by chromatin. (ku.dk)
  • The safest mechanism to repair a DSB is homologous recombination (HR). HR requires an identical or nearly identical DNA template, such as a sister chromatid or a homologous chromosome to retrieve the missing genetic information and accomplish error-free repair. (gatech.edu)
  • The synthesis of DNA that contributes to the process of double-strand break repair via homologous recombination. (zfin.org)
  • This method employs the use of oligonucleotides homologous to a region of interest that encompasses a desired mutation enabling DNA modification in a locus-specific manner. (igtrcn.org)
  • In the SDSA model, repair of double-stranded breaks occurs without the formation of a double Holliday junction, so that the two processes of homologous recombination are identical until just after D-loop formation. (wikipedia.org)
  • The invading 3' strand is thus extended along the recipient homologous DNA duplex by DNA polymerase in the 5' to 3' direction, so that the D-loop physically translocates - a process referred to as bubble migration DNA synthesis. (wikipedia.org)
  • Therefore, although SDSA produces non-crossover products because flanking markers of heteroduplex DNA are not exchanged, gene conversion may occur, wherein nonreciprocal genetic transfer takes place between two homologous sequences. (wikipedia.org)
  • The microscopy observations are confirmed using quantitative polymerase chain reaction measurements of the DNA degradation. (tudelft.nl)
  • Conformational transitions in mammalian DNA ligases III (LigIII) and IV (LigIV), as well as in PARP-1 [poly(ADP-ribose) polymerase-1], were analysed upon binding to double-stranded DNA by changes in tryptophan emission and FRET (Förster resonance energy transfer) from tryptophan to DNA-conjugated Alexa Fluor® 532. (portlandpress.com)
  • Based on sequence analysis, we propose a model of synthesis-dependent microhomology-mediated end joining (SD-MMEJ), in which de novo synthesis by an accurate non-processive DNA polymerase creates microhomology. (tufts.edu)
  • DNA polymerase lambda (pollambda) is a recently identified DNA polymerase whose cellular function remains elusive. (inserm.fr)
  • Importantly, we found that DNA polymerase delta (Pol δ) is critical for MMEJ, independent of microhomology length and base-pairing continuity. (elsevier.com)
  • Furthermore, mutations in Pol δ and DNA polymerase 4 (Pol λ), the DNA polymerase previously implicated inMMEJ, cause a synergistic decrease in MMEJ repair. (elsevier.com)
  • To test whether it was this other HR pathway that was rescuing DNA repair, the team used yeast that lacked the Rad51 paralogs. (news-medical.net)
  • Factors determining DNA double-strand break repair pathway choice in G2 phase," EMBO Journal , vol. 30, no. 6, pp. 1079-1092, 2011. (hindawi.com)
  • Contact with E. coli expressing this gene cluster causes DNA double-strand breaks and activation of the DNA damage checkpoint pathway, leading to cell cycle arrest and eventually to cell death. (sciencemag.org)
  • In this study, we report that the endo-exonuclease, a protein involved in the recombination repair process of the DNA double-stranded break pathway, is overexpressed in a variety of cancer cells and could represent an effective target for developing anticancer drugs. (aacrjournals.org)
  • This dual and opposing action of the DNA repair process indicated that, whereas DNA repair protein(s) could be a target for anticancer drug development, the choice of the DNA repair protein and its corresponding repair pathway as a target is highly critical. (aacrjournals.org)
  • The first step in this pathway is the recognition of the DSB and the resection of the 5′ strand to produce a 3′-OH overhang that can be recognized by the recombinase. (asm.org)
  • We genotyped 10 potentially functional single nucleotide polymorphisms (SNPs) in 7 DNA double-strand break repair pathway genes ( XRCC3 , BRCA2 , RAG1 , XRCC5 , LIG4 , XRCC4 and ATM ) in a case-control study including 384 glioma patients and 384 cancer-free controls in a Chinese Han population. (biomedcentral.com)
  • Comprehensive Mapping of Histone Modifications at DNA Double-Strand Breaks Deciphers Repair Pathway Chromatin Signatures. (physiciansweekly.com)
  • The MMR pathway also plays a role in maintaining the stability of certain types of repetitive DNA tracts ( 28 ). (asm.org)
  • Therefore, we asked if an alternative repair pathway provides a backup repair mechanism in DNA-PKcs- and Rad51-deficient ESCs. (tu-darmstadt.de)
  • In yeast, the D-loop is formed by strand invasion with the help of proteins Rad51 and Rad52, and is then acted on by DNA helicase Srs2 to prevent formation of the double Holliday junction in order for the SDSA pathway to occur. (wikipedia.org)
  • Srs2 promotes the non-crossover SDSA pathway, apparently by regulating RAD51 binding during strand exchange. (wikipedia.org)
  • DNA repair must take place within the context of chromatin, and it is therefore not surprising that many aspects of both chromatin components and proteins that modify chromatin have been implicated in this process. (nih.gov)
  • TALE binding to DNA is mediated by a central region of these proteins that contains as many as 30 tandem repeats of a 33- to 35-amino-acid-sequence motif ( Figure 1A ). (genetics.org)
  • The ability to predict the DNA binding specificity of native or artificial TALEs suggests a variety of applications for these proteins in the targeted modification of genomes. (genetics.org)
  • Surprisingly, they found that although the mutated helper proteins could not switch on Rad51 in a test tube, yeast cells with these mutations were still able to repair their DNA without problems. (news-medical.net)
  • This led the team to speculate that another group of helper proteins, which are present in the cell but absent in the test tube, was rescuing the DNA repair process. (news-medical.net)
  • Although these two groups of helper proteins were previously thought to function independently, our study shows that they actually work together to activate Rad51 in DNA repair,' explains senior author Hiroshi Iwasaki, Professor at the Tokyo Institute of Technology. (news-medical.net)
  • Polo SE, Jackson SP (2011) Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications. (springer.com)
  • Using a technique developed specifically for this project, the St. Jude researchers could determine when repair proteins arrived at or around the DNA break and evaluate its repair-even when particular proteins shifted away from the break to make room for others. (phys.org)
  • The findings are important because disruption of the precise movement of these repair proteins can cause mutations, cell death or cancer, and the ability to track the process so closely will give researchers critical insights into what can go wrong with DNA repair. (phys.org)
  • Prior to this work, there was no practical and efficient way to find and study the DNA repair proteins that organize themselves on and around a double-strand break in human cells," said Michael Kastan, M.D., Ph.D., St. Jude Cancer Center director. (phys.org)
  • The technique provides significantly more information about the proteins that repair DNA than is possible using the standard microscope-based approach previously used for such work. (phys.org)
  • A deficiency in two of these repair proteins, ATM and NBS1, leads to defects in double-strand break repair by disrupting the signaling processes triggered by the break. (phys.org)
  • and that ATM and NBS1 cooperate to disrupt nucleosomes-the compact packages formed when strands of DNA wind around proteins, called histones, like thread around a spool. (phys.org)
  • The researchers suggested that ATM had been displaced or moved so that the repair proteins could gain access to the damaged DNA site. (phys.org)
  • The team then used a biochemical technique called chromatin immunoprecipitation to collect and identify repair proteins and show where each one bound to the DNA. (phys.org)
  • Of note, specific mechanisms are required to process DSB ends containing covalently-bound proteins (such as Topoisomerase), DNA alterations (oxidation, methylation, hairpin formation, and others) and associated RNA molecules (e.g. (frontiersin.org)
  • The data on forum domains formed by DNA double-strand break (DSB) hotspots are reviewed including forum domain identification by pulsed-field gel electrophoresis, whole genome mapping of these domains using deep sequencing strategies, analysis of gene expression in forum domains, and binding of nuclear proteins to their boundaries. (springer.com)
  • In vitro experiments with recombinant human proteins show that Mre11 can cut the 5′-strand of a DNA duplex downstream of a break. (elifesciences.org)
  • Our data demonstrate that defects in double-strand break repair lead to an increase in genome instability, while drug resistance arises more rapidly in C. albicans strains lacking mismatch repair proteins or proteins central to double-strand break repair. (asm.org)
  • This active form of DNA-PK phosphorylate a variety of proteins including p53, XRCC4 proteins, etc. (nii.ac.jp)
  • DSB repair by transcript RNA in cis is promoted by the HR protein Rad52 but not Rad51, in agreement with the demonstration that the yeast and human Rad52 proteins efficiently catalyze annealing of RNA to a DSB-like DNA end in vitro. (gatech.edu)
  • The mechanisms involve the proteins and DNA sequences inside cells. (wikipedia.org)
  • One of the best-characterized chromatin modification events in DNA-damage responses is the phosphorylation of the SQ motif found in histone H2A or the H2AX histone variant in higher eukaryotes. (nih.gov)
  • These foci then play a role in recruiting DNA repair and damage-response factors and changing chromatin structure to accurately repair the damaged DNA. (bioone.org)
  • Shanbhag NM, Rafalska-Metcalf IU, Balane-Bolivar C, Janicki SM, Greenberg RA (2010) ATM-dependent chromatin changes silence transcription in cis to DNA double-strand breaks. (springer.com)
  • Rapid progress in the study on the association of histone modifications with chromatin remodeling factors has broadened our understanding of chromatin dynamics in DNA transactions. (mdpi.com)
  • BRCA1 is necessary for cellular processes ranging from cell cycle checkpoint control, DNA repair, regulation of transcription, protein ubiquitination, and apoptosis to chromatin remodeling ( 28 , 48 , 54 , 63 ). (asm.org)
  • At the break site, ATM autophosphorylates, allowing its activation and the following phosphorylation of several substrates in the surrounding chromatin. (wikipathways.org)
  • Histone modifications establish the chromatin states that coordinate the DNA damage response. (elifesciences.org)
  • The results further suggest the possible existence of units of higher order chromatin structure involved in monitoring DNA integrity. (rupress.org)
  • On the other hand, a reduced capacity in DNA repair process has been reported to play a vital role in genomic instability and cancer development. (aacrjournals.org)
  • Defects in the DNA repair may lead to cell death or genomic instability and development of cancer. (diva-portal.org)
  • A single I- Sce I homing endonuclease recognition site was introduced into the DNA of the chicken hepatoma cell line LMH by stable DNA transfection, and double-strand breaks were induced by transient expression of I- Sce I after transfection of an I- Sce I expression vector. (pnas.org)
  • Chen X, Niu H, Chung WH, Zhu Z, Papusha A, Shim EY, Lee SE, Sung P, Ira G (2011) Cell cycle regulation of DNA double-strand break end resection by Cdk1-dependent Dna2 phosphorylation. (springer.com)
  • Kaidi A, Weinert BT, Choudhary C, Jackson SP (2010) Human SIRT6 promotes DNA end resection through CtIP deacetylation. (springer.com)
  • CtIP is involved in the resection of broken DNA during the S and G2 phases of the cell cycle for repair by recombination. (elifesciences.org)
  • Acting with the MRN complex, it plays a particularly important role in handling complex DNA end structures by localised nucleolytic processing of DNA termini in preparation for longer range resection. (elifesciences.org)
  • DNA end resection can be broadly separated into three mechanistic stages: initial recognition of the DSB, short-range resection and long-range resection. (elifesciences.org)
  • In addition, we showed that in contrast to DSB repair by single strand DNA (ssDNA) oligonucleotides (oligos), RNA templated DSB repair is not dependent on factors that are major players in DNA end resection. (gatech.edu)
  • This result could be explained by a mechanism in which transcript RNA repairs a DSB in conditions of limited end resection via an inverse strand exchange reaction. (gatech.edu)
  • The 5' to 3' exonucleolytic resection of the DNA at the site of the break at the mating-type locus to form a 3' single-strand DNA overhang. (zfin.org)
  • Integration appeared to occur through nonhomologous end joining between the viral linear DNA ends and the I- Sce I-induced break, because small deletions or insertions were observed at the sites of end joining. (pnas.org)
  • In the absence of a repair template, broken chromosomes are rejoined by nonhomologous end joining, which often introduces short DNA insertions or deletions that create targeted gene knockouts. (genetics.org)
  • Miller KM, Tjeertes JV, Coates J, Legube G, Polo SE, Britton S, Jackson SP (2010) Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining. (springer.com)
  • The ubiquitylation of histone H2B by RNF20 E3 ligase was recently found to be a DNA damage-induced histone modification. (mdpi.com)
  • These repair events are absent in Ku80-, DNA-PKcs-, and DNA ligase IV-deficient cells but are present in RAD54 −/− cells. (aacrjournals.org)
  • XLF enhances ligation of DNA ends by DNA ligase IV (LIG4) and functionally interacts with KU70. (bham.ac.uk)
  • Eukaryotes possess multiple DNA ligases with distinct roles in DNA metabolism, with clear differences in the functions of DNA ligase orthologues between animals, yeast and plants. (biomedcentral.com)
  • Therefore, RNAi lines with reduced levels of AtLIG1 were generated to allow the roles and importance of Arabidopsis DNA ligase 1 in DNA metabolism to be elucidated. (biomedcentral.com)
  • Histone H2A phosphorylation in DNA double-strand break repair. (nih.gov)
  • Within minutes of the induction of DNA double-strand breaks in somatic cells, histone H2AX becomes phosphorylated at serine 139 and forms γ-H2AX foci at the sites of damage. (bioone.org)
  • Thurn KT, Thomas S, Raha P, Qureshi I, Munster PN (2013) Histone deacetylase regulation of ATM-mediated DNA damage signaling. (springer.com)
  • Burma S, Chen BP, Murphy M, Kurimasa A, Chen DJ (2001) ATM phosphorylates histone H2AX in response to DNA double-strand breaks. (springer.com)
  • This unit describes immunocytochemical detection of phosphorylated histone H2AX for revealing the presence of DNA double-strand breaks. (wiley.com)
  • The protocol describes the immunocytochemical detection of histone H2AX phosphorylated on Ser- 139 combined with measurement of DNA content to identify cells that have DNA double-strand breaks and to concurrently assess their cell cycle phase. (wiley.com)
  • Double-strand breaks were assessed by the detection of phosphorylated histone H2AX foci (γH2AX). (environmental-expert.com)
  • To investigate the timing of and requirements for double-strand break formation during Drosophila meiosis, we used an antibody that recognizes a histone modification at double-strand break sites, phosphorylation of HIS2AV (γ-HIS2AV). (biologists.org)
  • Overall the results help to illustrate how histone modifications and the DNA damage repair mechanisms and checkpoints work in concert to suppress cancer. (elifesciences.org)
  • Pharmacodynamic studies compared histone acetylation, apoptosis, proliferation, and DNA damage in vitro and in vivo . (aacrjournals.org)
  • A lack of functioning ATM causes ataxia-teleangiectasia, a disease that causes a variety of debilitating problems, such as neurodegeneration, cancer and sensitivity to irradiation leading to double-strand breaks that are not repaired," Kastan said. (phys.org)
  • Transient inhibition of ATM and DNA-PK during mitosis before irradiation results in the increase of persistent IRIF 24 h after treatment. (rupress.org)
  • Furthermore, in normal cells difficulty in repairing clustered breaks was observed as a large fraction of γ-H2AX foci remaining 24 h after irradiation with high-LET ions. (diva-portal.org)
  • This modification is an early response to the induction of DNA damage, and occurs in a wide range of eukaryotic organisms, suggesting an important conserved function. (nih.gov)
  • G. E. Iliakis, G. E. Pantelias, R. Okayasu, and W. F. Blakely, "Induction by H 2 O 2 of DNA and interphase chromosome damage in plateau- phase Chinese hamster ovary cells," Radiation Research , vol. 131, no. 2, pp. 192-203, 1992. (hindawi.com)
  • induction of DNA double-strand breaks associated with the down-regulation of the DNA repair gene Rad52. (aacrjournals.org)
  • Its mechanism of action involves the induction of DNA double-strand breaks, suggesting rational combinations with DNA active drugs or radiation. (aacrjournals.org)
  • Characterization of the NCS-induced DNA damage response in terms of cell viability and early induction of DSB sensors in ALS- and HC-hMSC populations. (biologists.org)
  • The cells were treated with 50 ng/ml NCS and were incubated for 1, 2, 4, 12 and 24 h post DNA damage induction in the presence or absence of the apoptosis inhibitor Q-VAD-OPH at 20 μM or of the autophagy inhibitor 3MeA at 10 mM. (biologists.org)
  • Recently, unexpected links between these double-stranded break-repair systems, and several human genome instability and cancer predisposition syndromes, have emerged. (nih.gov)
  • Multiple levels of regulation of the break processing ensure faithful DSB repair, preventing chromosome rearrangements, and genome instability. (frontiersin.org)
  • Our study demonstrated that BRCA1 may interfere with yeast DNA repair functions that are active in S-phase causing high level of GR. In addition, we confirmed here that yeast could be a reliable model to investigate the mechanism and genetic requirements of BRCA1-induced genome instability. (unboundmedicine.com)
  • The DNA-PK holoenzyme consists of the Ku70/80 heterodimer and a 470-kD catalytic subunit (DNA-PK CS ) with serine/threonine protein kinase activity. (rupress.org)
  • Double stranded DNA dependent protein kinase (DNA-PK) consist of DNA-PKcs (catalytic subunit) and Ku70/80 heterodimer (DNA double strand break end binding subunit). (nii.ac.jp)
  • Publications] Ihara,M.: 'Heat sensitivity of double-stranded DNA-dependent protein kinase(DNA-PK) activity'Int.J.Radiat.Biol. (nii.ac.jp)
  • Publications] Okumura, Y.: 'Heat inactivation of DNA-dependent protein kinase : Possible mechanism of hyperthermic radiosensitization. (nii.ac.jp)
  • Interestingly, inhibition of DNA-dependent protein kinase indicates that NMDAR-mediated transcription involves factors required in DSB repair, suggesting an important role for DNA repair in NMDAR-mediated transcriptional regulation. (tu-darmstadt.de)
  • Once inside the plant cell, TALEs enter the nucleus, bind effector-specific DNA sequences, and transcriptionally activate gene expression. (genetics.org)
  • Expression of the HO gene from a galactose-inducible promoter allowed efficient DNA cleavage at a single site in large populations of cells. (genetics.org)
  • The break is repaired by copying the endonuclease gene. (els.net)
  • TY - JOUR T1 - Effect of BRCA1 missense variants on gene reversion in DNA double-strand break repair mutants and cell cycle-arrested cells of Saccharomyces cerevisiae. (unboundmedicine.com)
  • However, a decreased rate of repair of DNA double-strand breaks in strains lacking the mre11 gene was observed using pulsed-field gel electrophoresis. (asm.org)
  • A DNA substrate containing a thymidine kinase (tk) gene fused to a neomycin-resistance (neo) gene was stably integrated into cells. (biomedsearch.com)
  • The gene for this protein, which impedes the proliferation of cells with genomic aberrations, such as double-strand breaks, is mutated in most cancers. (elifesciences.org)
  • Most important are DNA repair ( 1 ) and radiation-induced signaling mechanisms that cause changes in gene expression, cell cycle progression, and apoptosis ( 2 ). (aacrjournals.org)
  • RePub, Erasmus University Repository: Sequence conservation of the rad21 Schizosaccharomyces pombe DNA double-strand break repair gene in human and mouse. (eur.nl)
  • The rad21 gene of Schizosaccharomyces pombe is involved in the repair of ionizing radiation-induced DNA double-strand breaks. (eur.nl)
  • Here, we identified an elephant A3Z1 gene, related to human APOBEC3A and showed that it could efficiently deaminate cytidine, 5-methylcytidine and produce DNA breaks leading to massive apoptosis, similar to other mammalian APOBEC3A enzymes where body mass varies by up to four orders of magnitude. (pasteur.fr)
  • They mentioned that in the dearth of naturally DNA-modifying catalysts, RNA has a variety of enzymatic options for modulating its biological activity with a temporal resolution without the risk of permanently modifying the genome therefore a safer option for gene therapies, for example. (igtrcn.org)
  • Engineered nucleases that cleave specific DNA sequences in vivo are valuable reagents for targeted mutagenesis. (genetics.org)
  • The animal model clearly highlights the significant contribution of polyamines to the DNA repair in vivo. (aacrjournals.org)
  • Not much is known about the in vivo dynamics of enzyme-DNA complex formation upon the onset of a DSB event. (rupress.org)
  • When root or sepal cells, or undifferentiated suspension cells, were treated with DSB inducers, they displayed increased cell size and DNA ploidy. (pnas.org)
  • In this study, we found that Arabidopsis cells treated with DSB inducers displayed increased cell size and DNA ploidy without a concomitant change in chromosome number. (pnas.org)
  • They genetically engineered yeast cells so that they lacked either Module 1 or Module 2 of Swi5-Sfr1 and found that this prevented DNA repair by HR. This shows that both modules are needed for Rad51 to switch on HR repair. (news-medical.net)
  • To counteract genotoxic threats, cells are equipped with a diverse set of DNA damage signaling and repair mechanisms, collectively known as the DNA damage response (DDR) ( 1 ). (frontiersin.org)
  • Consequently, cancer cells become even more dependent on DNA repair mechanisms to survive and proliferate. (frontiersin.org)
  • This could lead to novel ways to make cancer cells more sensitive to therapy by blocking their ability to repair double-stranded breaks caused by chemotherapy or radiation. (phys.org)
  • Olive PL, Banath JP (2006) The comet assay: a method to measure DNA damage in individual cells. (springer.com)
  • However, double-strand breaks can also be intrinsic, occurring in healthy, nontreated cells for a variety of reasons, and are generated in the course of DNA fragmentation in apoptotic cells. (wiley.com)
  • The unit presents strategies to distinguish radiation- or drug-induced breaks from those intrinsically formed in untreated cells or associated with apoptosis. (wiley.com)
  • D) Radiosensitivity of asynchronous and mitotic cells pretreated for 1 h with DMSO or a combination of ATM and DNA-PK inhibitors and then exposed to various doses of IR. (rupress.org)
  • The aim of this study was to evaluate the DNA damage induced by low and high linear energy transfer radiation in two related cell lines with different radiation sensitivity, CHO10B2 and irs-20 cells (defective in DNA-PKcs). (environmental-expert.com)
  • As DNA repair is regulated by cell cycle, we determined the effect on GR of BRCA1 variants in cell cycle-arrested RSYwt cells. (unboundmedicine.com)
  • Detection of γ‑H2AX using western blot analysis at 0, 0.5, 1, 6 and 24 h following the exposure of cervical cancer cells to X‑rays illustrated that eIF4A1‑knockdown results in postponed radiation‑induced DNA double strand break (DSB) repair. (spandidos-publications.com)
  • It is critical that the genomic integrity of the cells remains intact and that the DNA repair systems are fully functional. (muni.cz)
  • In agreement, SETD2-mutant clear cell renal cell carcinoma (ccRCC) cells displayed impaired DNA damage signaling. (elifesciences.org)
  • Normal wear and tear, exposure to chemicals, and ultraviolet light can all damage DNA, so cells rely on a range of sensors and mechanisms to detect and repair damaged DNA. (elifesciences.org)
  • Cells also package DNA molecules inside structures called histones to protect them against damage. (elifesciences.org)
  • These clusters are the most actively transcribed DNA regions in cells, as well as the most fragile sites in human chromosomes. (springer.com)
  • A) The cells were treated with 50, 150, 300 and 500 ng/ml NCS for 30 min to induce DNA damage, rinsed and then kept in culture with fresh medium for 24 h. (biologists.org)
  • Cells were then fixed and the DNA damage response in terms of cell viability was quantified for the total number of nuclei using a living and dead fluorescence assay by staining the cells in microscopy-grade 96-well plates with a mix of Calcein-AM for live cells, propidium iodide (PI) for dead cells, and Hoechst 33342 to label all nuclei. (biologists.org)
  • To prevent the transmission of damaged genomic material between generations, cells require a system for accommodating DNA repair within their cell cycles. (prolekare.cz)
  • SWR1-dependent incorporation of Htz1 (H2A.Z) is necessary for break relocation to either site in both G1- and S-phase cells. (uzh.ch)
  • Moreover, trifluoperazine also increases the longevity of bleomycin-induced DNA strand breaks in U1810 cells, as shown by both comet assay and fraction of activity released (FAR)-assay. (diva-portal.org)
  • We propose that TFP might be capable of inhibiting one or more elements of the DNA DSB repair machinery, thereby increasing the cytotoxicity of bleomycin in lung cancer cells. (diva-portal.org)
  • In many organisms, cells deficient in DNA mismatch repair (MMR) exhibit a mutator phenotype in which the rate of spontaneous mutation is greatly elevated ( 6 , 10 ). (asm.org)
  • We analyzed the heat sensitivity of DNA-PK activity in hybrid cells and the possible restoration of this activity with extracts from scid cells (defective in DNA-PKcs). (nii.ac.jp)
  • The cell extract from scid cells or sxi-3 cells was added to heat-treated hybrid cell extracts, and the DNA-PK activity was assayed. (nii.ac.jp)
  • When hybrid cells were heated at 44℃ for 15 min, DNA-PK activity was reduced to undetectable levels. (nii.ac.jp)
  • DNA double strand breaks was repaired by two phase, namely fast repair and slow repair in hybrid cells. (nii.ac.jp)
  • Analysis of Top1‐linked DNA from pull‐down experiments revealed that Top1 is covalently linked to the end of DNA in RNase H2 ‐deficient yeast cells, supporting this model. (embopress.org)
  • In response to DNA damage, G1/S and G2/M checkpoints activities prevent the progression of the cells to the next cell cycle phase. (tu-darmstadt.de)
  • In order to define the molecular structure of DNA double strand breaks requiring ATM activity we examined repair of DNA double strand breaks induced by different restriction endonucleases in normal human diploid cells treated with or without ATM-specific inhibitor. (altmetric.com)
  • Positive regulation of DNA double strand break repair activity during differentiation of long life span cells: the example of adipogenesis. (inserm.fr)
  • When DNA double-strand breaks are introduced into specific partial nuclear volumes of cells by means of a pulsed microbeam laser, γ-H2AX foci form at these sites. (rupress.org)
  • In mitotic cells from cultures exposed to nonlethal amounts of ionizing radiation, γ-H2AX foci form band-like structures on chromosome arms and on the end of broken arms. (rupress.org)
  • Junctions between the 3' end of the provirus and the host DNA were analyzed in control cells, mutant cell lines, and complemented cell lines transduced with the HIV-based vector. (biomedcentral.com)
  • On the contrary, host cells have also evolved to maintain cellular genomic stability and suppress carcinogenesis through multifaceted cellular DNA damage response (DDR). (pirbright.ac.uk)
  • When cells were treated with tricostatin A (TSA) and the histones became hyperacetylated, the amount of γ-H2AX-bound DNA increased and the retained RIND-EDSBs were rapidly repaired. (biomedcentral.com)
  • Certain mechanisms are present to prevent cells from indefinite division, which is mostly done by programmed failure in DNA synthesis. (wikipedia.org)
  • The withdrawal process also prevents diseased cells, or cells with mutated or damaged DNA, from continuing to divide and increasing the percentage of abnormal cells inside the body. (wikipedia.org)
  • The results were striking: in yeast with mutant Swi5-Sfr1 and no Rad51 paralogs, the DNA damage was much more severe. (news-medical.net)
  • Rad52 was shown to be a DNA binding protein that can anneal ssDNA in vitro and in its absence Rad51 fails to bind to the single-stranded DNA tails. (brandeis.edu)
  • Rad51 may be involved in strand invasion or strand exchange, and hence might not be expected to play a role in SSA, where two strands interact by intertwining around each other. (brandeis.edu)
  • Furthermore, our in vitro reconstitution system and functional analyses demonstrated that polyamines significantly enhance RAD51-mediated DNA strand exchange reaction. (aacrjournals.org)
  • Importantly, we reveal that the stimulatory effect of polyamines by RAD51 stems from the enhancement of duplex DNA captures in the DNA exchange reaction. (aacrjournals.org)
  • The involvement of a crossover structure and a recombinase such as RecA ( Bacteria ), RadA ( Archaea ), or Rad51 ( Eukarya ) is common to both HR and extended-synthesis-dependent strand annealing, and the processing of double-stranded DNA ends to produce a 3′ overhang is found in HR, synthesis-dependent strand annealing, and extended-synthesis-dependent strand annealing ( 45 ). (asm.org)
  • Furthermore, mutations in Drosophila Rad54 ( okr ) and Rad51 ( spnB ) homologs cause delayed and prolonged γ-HIS2AV staining, suggesting that double-strand break repair is delayed but not eliminated in these mutants. (biologists.org)
  • These are stabilised by RPA and then bound by Rad51, which forms nucleoprotein filaments that undergo strand invasion with the sister chromatid, eventually leading to DNA repair without loss of genetic information ( Kowalczykowski, 2015 ). (elifesciences.org)
  • Top1‐induced DNA damage at ribonucleotide incorporation sites requires Rad51 and Rad52 for repair. (embopress.org)
  • However, inhibition of PARP1 induced an additional significant repair defect in DNA-PKcs- and Rad51-inhibited ESCs, not in NSCs. (tu-darmstadt.de)
  • Assembly of a nucleoprotein filament comprising single-stranded DNA (ssDNA) and the RecA homolog, Rad51, is a key step necessary for homology search during recombination. (wikipedia.org)
  • M. Isildar, M. N. Schuchmann, D. Schulte-Frohlinde, and C. Von Sonntag, " γ -Radiolysis of DNA in oxygenated aqueous solution: alterations at the sugar moiety," International Journal of Radiation Biology , vol. 40, no. 4, pp. 347-354, 1981. (hindawi.com)
  • P. L. Olive, "The role of DNA single- and double-strand breaks in cell killing by ionizing radiation," Radiation Research , vol. 150, supplement 5, pp. (hindawi.com)
  • Radiation-induced DNA double-strand breaks after myocardial scintigraphy. (knowcancer.com)
  • DNA double-strand breaks will be measured before and up to 48 hours after radiation. (knowcancer.com)
  • Conventional treatment modalities such as radiation therapy and certain forms of chemotherapy have been built on the premise to force DNA damage-induced cell death. (frontiersin.org)
  • It could also suggest new strategies for enhancing repair of double-stranded DNA caused by radiation, natural oxidants in food or the body and other toxins that can cause disease and aging. (phys.org)
  • And a lack of NBS1 causes Nijmegen breakage syndrome, another disease that leaves its victims at high risk for cancer and higher sensitivity to DNA-damaging radiation. (phys.org)
  • Double-strand breaks indicate DNA damage induced by ionizing radiation or by treatment with antitumor drugs such as DNA topoisomerase inhibitors. (wiley.com)
  • It is particularly essential following exposure to ionizing radiation, which has been shown to produce extensive DNA fragmentation ( 11 , 14 ). (asm.org)
  • Similar to DNA damage-triggered stress responses, signal mechanisms originating from activated cell receptors also affect the cellular susceptibility to radiation ( 9 , 10 ). (aacrjournals.org)
  • A statistically significant increase in formation of double-strand breaks and apoptosis was detected in samples after X-ray radiation with 10 - 200 mGy compared to the control. (emf-portal.org)
  • Therefore, the authors conclude that any generation of double-strand breaks and apoptosis in fetal mouse brain by an exposure to magnetic fields is lower than by radiation with 10 mGy X-rays . (emf-portal.org)
  • Agents such as cisplatin induce DNA alteration in part by cross-linking DNA strands and inhibition of the subsequent enzymatic processing of the DNA-damaging sites by DNA repair enzymes ( 3 -5 ). (aacrjournals.org)
  • In contrast, in NSCs, DSB repair was almost stalled after inhibition of DNA-PKcs. (tu-darmstadt.de)
  • In addition, the investigators showed that ATM initially binds to DNA both at the site of the break as well as on each side of it. (phys.org)
  • Because Ku70/80 has much higher affinity for DNA ends than DNA-PK CS , this heterodimer most likely binds to DNA termini first and subsequently attracts DNA-PK CS toward the DSB. (rupress.org)
  • Xrs2 binds DNA and Mre11 and aids in the localization of the complex to the DSB as well as the stimulation of the Mre11 exonuclease ( 38 ). (asm.org)
  • Mre11 binds to DSB ends and has both double-stranded 3'-5' exonuclease activity and single-stranded endonuclease activity (By similarity). (uniprot.org)
  • Using in vitro assays, we find that purified recombinant PtCtIP preferentially binds to double-stranded DNA substrates but does not contain intrinsic nuclease activity. (bioportfolio.com)
  • The protein complex binds two short DNA duplexes with high affinity and bridges DNA molecules in trans. (elifesciences.org)
  • Recently, we established a method for the detection of DNA methylation levels at sites close to endogenous DNA double strand breaks (EDSBs), and found that those sites have a higher level of methylation than the rest of the genome. (biomedcentral.com)
  • Breaks in both DNA strands are a particularly dangerous threat to genome stability. (nih.gov)
  • The DSB response, which requires end-processing and RecA or short RecO-independent RecA filaments, highlights the importance of guarding genome stability by modulating the DNA damage responses. (csic.es)
  • This has important implications for genome stability, because ribonucleotides are more susceptible to spontaneous hydrolysis (Li & Breaker, 1999 ), generating DNA ends that cannot be directly ligated. (embopress.org)
  • Our study provides proof and initial characterization of a new mechanism of DNA repair and HR mediated by RNA in yeast, and unravels novel aspects in the complex relationship between RNA and DNA in genome stability. (gatech.edu)
  • Possibly the most harmful type of lesion the DNA may undergo is the breakage of the two strands (DSB) and the repair of this damage is of great importance to maintain genome stability. (igtrcn.org)
  • Then, starting from the nick, the nucleases Mre11, Exo1, Dna2, in cooperation with Sgs1 helicase (BLM in human), degrade DNA strand in both the directions, creating the 3′ ssDNA filament. (frontiersin.org)
  • However, the affinity for linear DNA molecules is increased if the DNA terminates with complex structures including forked ssDNA overhangs and nucleoprotein conjugates. (elifesciences.org)
  • Subsequent studies of meiotic recombination in S. cerevisiae found that non-crossover products appear earlier than double-Holliday junctions or crossover products, challenging the previous notion that both crossover and non-crossover products are produced by double-Holliday junctions and leading the authors to propose that non-crossover products are generated through SDSA. (wikipedia.org)
  • The DNA damage checkpoint in metazoans ensures genome integrity by delaying cell-cycle progression to repair damaged DNA or by inducing apoptosis. (pnas.org)
  • To this end, cell viability, proliferation, and apoptosis as well as DNA damage-related stress responses were investigated. (aacrjournals.org)
  • Increased apoptosis and DNA double-strand breaks in the embryonic mouse brain in response to very low-dose X-rays but not 50 Hz magnetic fields. (emf-portal.org)
  • DNA double-strand breaks and apoptosis in fetal mouse brain as possible effects of an whole body exposure to a 50 Hz magnetic field or X-rays should be investigated. (emf-portal.org)
  • Ataxia telangiectasia mutated activation by transcription- and topoisomerase I-induced DNA double-strand breaks," EMBO Reports , vol. 10, no. 8, pp. 887-893, 2009. (hindawi.com)
  • Transcription-dependent degradation of topoisomerase I-DNA covalent complexes," Molecular and Cellular Biology , vol. 23, no. 7, pp. 2341-2350, 2003. (hindawi.com)
  • Other anticancer agents such as etoposide interfere with the topoisomerase enzymes, which modify DNA topology ( 6 , 7 ). (aacrjournals.org)
  • Ribonuclease activity of topoisomerase I (Top1) causes DNA nicks bearing 2′,3′‐cyclic phosphates at ribonucleotide sites. (embopress.org)
  • Topoisomerase I (Top1) is known to generate single‐strand breaks at sites of newly incorporated and unrepaired ribonucleotides in DNA. (embopress.org)
  • The Sgs1 helicase forms a conserved complex with the topoisomerase III (Top3)-RMI1 heterodimer (that catalyzes DNA single strand passage). (wikipedia.org)
  • However, it is noteworthy that, unlike mammalian ATR knockouts, Arabidopsis atr mutants are viable ( 9 ), suggesting that regulatory mechanisms underlying the DNA damage response are diverged between plants and animals. (pnas.org)
  • The fundamental mechanisms of DNA repair are highly conserved from yeast to humans. (news-medical.net)
  • There are various mechanisms that work in the processing of these breaks, sometimes in collaboration or competition with each other. (els.net)
  • DNA repair mechanisms are crucial for the maintenance of genomic stability and are emerging as potential therapeutic targets for cancer. (aacrjournals.org)
  • In this review, we first discuss insights into the mechanisms of endogenous DSB formation, showcasing the trade-off between essential DNA transactions and the intrinsic challenges that these processes impose on genomic integrity. (mdpi.com)
  • Interestingly, we detected a low (10-25% of wildtype) number of γ-HIS2AV foci in c(3)G mutants, which fail to assemble synaptonemal complex, suggesting that there may be both synaptonemal complex-dependent and synaptonemal complex-independent mechanisms for generating double-strand breaks. (biologists.org)
  • An important product is 3-methyladenine (m3A), which in Escherichia coli is removed by m3A-DNA glycosylase I (Tag) and II (AlkA). (medworm.com)
  • The formation of 3 single-stranded DNA overhangs is a first and essential step during homology-directed repair of double-stranded breaks (DSB) of DNA, a task that in Escherichia coli is performed by RecBCD. (tudelft.nl)
  • 1. Eykelenboom JK, Blackwood JK, Okely E, Leach DR. SbcCD causes a double-strand break at a DNA palindrome in the Escherichia coli chromosome. (prolekare.cz)
  • The use of photobleaching techniques allowed us to determine that the kinase activity and phosphorylation status of DNA-PK CS influence the stability of its binding to DNA ends. (rupress.org)
  • In this study, we tested directly whether sites of cellular DNA damage, namely double-strand breaks, are specific targets for viral DNA integration. (pnas.org)
  • Indirect evidence suggests that at least two types of linear double-strand viral DNAs are substrates for integration. (pnas.org)
  • ATM and ATR relay the damage signal to transducer kinases Chk2 and Chk1, respectively, which then amplify the signal and regulate an overlapping set of substrates that trigger cell-cycle arrest and DNA repair ( 1 ). (pnas.org)
  • While RAD52 is clearly required for SSA using ura3 and leu2 substrates it has been reported that RAD52 is not required for SSA events located within the ribosomal DNA array (100 repeats of a 9 kb sequence) and is partially required for SSA within a CUP1 array of repeats. (brandeis.edu)
  • Deoxyribonucleic acid (DNA) double‐strand breaks, which are caused by many factors such as chemical treatments, radiations and, often, biological factors, are lethal events in organisms carrying DNA as their genome, which include bacteria. (els.net)
  • The relationship between synaptonemal complex formation (synapsis) and double-strand break formation (recombination initiation) differs between organisms. (biologists.org)
  • DNA ligases play essential roles in all organisms by maintaining the physical structure of DNA. (biomedcentral.com)
  • The DNA structure in these organisms are in the form of circular chromosomes, meaning there would be no "ends" appearing in their DNA. (wikipedia.org)
  • It emerged that SETD2 must be present for DNA repair to take place: the SETD2 modifies the histones so that they can recruit the enzymes that repair the DNA via the template approach (which is relatively error free). (elifesciences.org)
  • Indeed, the mutagenic activity of some APOBEC3 enzymes has been shown to introduce somatic mutations into genomic DNA. (pasteur.fr)
  • However, XRCC4 later takes the place of ATM molecules at the break while the ATM molecules on either side of the break stay in place. (phys.org)
  • Moreover, we also take into consideration recent evidence regarding functional interplay between DSB repair and RNA molecules nearby the break site. (frontiersin.org)
  • MR adopts an open form with a central Mre11 nuclease dimer and two peripheral Rad50 molecules, a form suited for sensing obstructed breaks. (rcsb.org)
  • β is estimated to be about 2.5 h and the corresponding rate of break repairs (μ) is estimated to be about 0.4 break repairs/h on different DNA molecules. (environmental-expert.com)
  • ATP binding to the two Rad50 subunits induces a rotation of the Mre11 helix-loop-helix and Rad50 coiled-coil domains, creating a clamp conformation with increased DNA-binding activity. (rcsb.org)
  • Both native and custom TALE-nuclease fusions direct DNA double-strand breaks to specific, targeted sites. (genetics.org)
  • In particular, the DNA recognition domain could direct a fused nuclease to a specific DNA sequence. (genetics.org)
  • ZFN, zinc finger nuclease containing the Zif268 DNA binding domain as a positive control ( P orteus and B altimore 2003 ). (genetics.org)
  • Mre11 is a nuclease with double-stranded DNA exonuclease and single-stranded DNA endonuclease activities as well as a helicase. (asm.org)
  • Mre11 dimers coordinate DNA end bridging and nuclease processing in double-strand-break repair. (harvard.edu)
  • The transcription factor p53, cyclin-dependent kinase (CDK) inhibitor p21, and Cdc25 phosphatase are downstream regulators that control cell-cycle arrest in response to DNA damage. (pnas.org)
  • The BRCA1 protein becomes phosphorylated in response to DNA damage, but the effects of phosphorylation on recombinational repair are unknown. (asm.org)
  • Interestingly, genes that were deregulated in the OM possessed molecular functions such as DNA double-strand break (DSB) repair ( Rad18 , Brip1 , and Brcc3 ), cell cycle progression ( Cyce1 , Ccna2 , and Ccnb1 ), G 2 /M arrest in response to DNA damage ( Chek1 and Wee1 ), and p53-associated factors ( Phlda3 and Ccng1 ). (go.jp)
  • To meet the challenge of correct classification, flow cytometry-based functional variant analyses (FVAs) were developed to determine whether variants in DSB repair genes disrupted the binding of BRCA1 to BARD1, PALB2, BRCA2 and FANCD2, phosphorylation of p53 or BRCA1 nuclear localization in response to DNA damage caused by diepoxybutane, mitomycin C and bleomycin. (elsevier.com)
  • The results suggest that integration of hepadnaviral DNA in infected livers occurs at sites of DNA damage and may indicate the presence of more widespread genetic changes caused by viral DNA integration itself. (pnas.org)
  • Damaged DNA needs to be repaired to prevent loss or incorrect transmission of genetic information. (pnas.org)
  • A particularly hazardous type of DNA lesion is the double-strand break (DSB), which can lead to large genetic alterations if not repaired accurately. (springer.com)
  • Genetic variations in DNA double-strand break repair genes can influence the ability of a cell to repair damaged DNA and alter an individual's susceptibility to cancer. (biomedcentral.com)
  • Therefore, the wearing off of DNA would not occur, and the genetic information would remain the same, and no withdrawal would happen. (wikipedia.org)
  • The results suggest that MR is an ATP-controlled transient molecular clamp at DNA double-strand breaks. (rcsb.org)
  • The enzyme endo-exonuclease has been shown to function in DNA DSB repair and recombination ( 15 ). (aacrjournals.org)
  • Comparative sequence analyses among plants, yeast, and animals indicate that some of the factors involved in DNA damage checkpoint and DSB repair systems are conserved between vertebrates and plants ( 7 ). (pnas.org)
  • At a DNA double-strand break (DSB), potentially lost sequence information cannot be recovered from the same DNA molecule. (nih.gov)
  • Sequence analysis of genomic DNA from ILV1 revertant clones showed that BRCA1-induced ilv1-92 reversion by base substitution when GR is at least 6-fold over the control. (unboundmedicine.com)
  • Either single-strand annealing (SSA) repair or microhomology-mediated end joining occurs 'in register' between two Alu elements when Alu sequence divergence is low. (prolekare.cz)
  • Evolving DNA Repair Polymerases: From Double-Strand Break Repair to Base Excision Repair and VDJ Recombination, New Research Directions in DNA Repair Clark Chen, IntechOpen, DOI: 10.5772/53908. (intechopen.com)
  • Chain-terminating nucleoside analogs (CTNAs), which cannot be extended by DNA polymerases, are widely used as antivirals or anti-cancer agents, and can induce cell death. (bioportfolio.com)
  • Meyer, D, Fu, BXH & Heyer, WD 2015, ' DNA polymerases δ and λ cooperate in repairing double-strand breaks by microhomology-mediated end-joining in Saccharomyces cerevisiae ', Proceedings of the National Academy of Sciences of the United States of America , vol. 112, no. 50, pp. (elsevier.com)
  • Rad50 Is Not Essential for the Mre11-Dependent Repair of DNA Double-Strand Breaks in Halobacterium sp. (asm.org)
  • These observations led to the hypothesis that Mre11 is essential for the repair of DNA double-strand breaks in Halobacterium , whereas Rad50 is dispensable. (asm.org)
  • Part of the Rad50/Mre11 complex, which is involved in the early steps of DNA double-strand break (DSB) repair. (uniprot.org)
  • Moreover, mutation of the evolutionarily conserved C-terminal 'RHR' motif abrogates DNA binding of PtCtIP but not its ability to functionally interact with Mre11. (bioportfolio.com)
  • We investigated the acquisition of drug resistance in the DNA repair mutants and found that deletion of mre11 Δ/ mre11 Δ, rad50 Δ/ rad50 Δ, or rad52 Δ/ rad52 Δ leads to an increased susceptibility to fluconazole. (asm.org)
  • DNA synthesis errors associated with double-strand-break repair. (genetics.org)
  • In this study, synthesis of conductive metal nanowires by using aligned and immobilised DNA strand on solid substrate is reported. (environmental-expert.com)
  • Synthesis-Dependent Microhomology-Mediated End Joining: A Unifying Model For Multiple DNA Double Strand Break Repair Outcomes. (tufts.edu)
  • The association of Pol δ depended on RAD1, which encodes the flap endonuclease needed to cleave MMEJ intermediates before DNA synthesis. (elsevier.com)
  • In 1994, studies of double-strand gap repair in Drosophila were found to be incompatible with the double-Holliday junction model, leading researchers to propose a model they called synthesis-dependent strand annealing. (wikipedia.org)
  • Thus DNA synthesis fills in gaps left over from annealing, and extends both ends of the still present single stranded DNA break, ligating all remaining gaps to produce recombinant non-crossover DNA. (wikipedia.org)
  • We show that DNA-PK CS accumulates at DSB sites in a Ku80-dependent manner, and that neither the kinase activity nor the phosphorylation status of DNA-PK CS influences its initial accumulation. (rupress.org)
  • DNA double‐strand breakage and its consequences in bacteria may provide a good model system to analyse the dynamic relationship between life, death and evolution. (els.net)
  • DNA double‐strand breakage may switch on programmes of cell death in bacteria. (els.net)
  • Repair of DNA double‐strand breakage provides accurate products and innacurate products for host genome. (els.net)
  • The reverted allele was found predominantly on the chromosome that experienced the DNA cleavage. (genetics.org)
  • Finally, the DSB-induced cohesion is not limited to broken chromosomes but occurs also on unbroken chromosomes, suggesting that the DNA damage checkpoint through Eco1 provides genome-wide protection of chromosome integrity. (sciencemag.org)
  • Spontaneous mutations, including loss of heterozygosity, chromosome translocation and DNA deletion, are associated with global hypomethylation in cancer. (biomedcentral.com)
  • Single strand annealing (SSA) is a process that is initiated when a double strand break is made between two repeated sequences oriented in the same direction. (brandeis.edu)
  • Single stranded regions are created adjacent to the break that extend to the repeated sequences such that the complementary strands can anneal to each other. (brandeis.edu)
  • A role for DNA mismatch repair protein Msh2 in error-prone double-strand-break repair in mammalian chromosomes. (biomedsearch.com)
  • Single strand annealing was also characterized in several other respects. (brandeis.edu)
  • Interestingly, DNA-PKcs inhibitor induced a temporary repair defect followed by an efficient repair to the background DSB levels in ESCs. (tu-darmstadt.de)
  • Interestingly, the up-regulation of DNA-PK does not regulate the differentiation program itself. (inserm.fr)
  • These repair systems lessen the efficiency of cancer therapies that are dependent on chemotherapeutics, which target DNA. (aacrjournals.org)
  • The data show that lovastatin has multiple inhibitory effects on IR-stimulated DNA damage-dependent stress responses in HUVEC. (aacrjournals.org)
  • The decreased DNA-PK activity could be restored in concentration-dependent manner with the addition of scid cell extract. (nii.ac.jp)
  • In contrast, a sub-fraction of breaks is repaired with slow kinetics in an ATM-dependent manner. (tu-darmstadt.de)
  • Ku is a 5′-dRP/AP lyase that excises nucleotide damage near broken ends," Nature , vol. 464, no. 7292, pp. 1214-1217, 2010. (hindawi.com)
  • Synapsis is mediated solely by Polμ, facilitated by single-nucleotide homology at the break site, wherein both ends of the discontinuous template strand are stabilized by a hydrogen bonding network. (rcsb.org)
  • Rad52 isolated from humans possesses the ability to bind to the ends of DNA. (brandeis.edu)