DNA Repair: 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.DNA Repair Enzymes: Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.DNA Damage: 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.Ultraviolet Rays: 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.DNA-Binding Proteins: 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.DNA Breaks, Double-Stranded: Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.DNA Glycosylases: A family of DNA repair enzymes that recognize damaged nucleotide bases and remove them by hydrolyzing the N-glycosidic bond that attaches them to the sugar backbone of the DNA molecule. The process called BASE EXCISION REPAIR can be completed by a DNA-(APURINIC OR APYRIMIDINIC SITE) LYASE which excises the remaining RIBOSE sugar from the DNA.Recombinational DNA Repair: Repair of DNA DAMAGE by exchange of DNA between matching sequences, usually between the allelic DNA (ALLELES) of sister chromatids.Rad52 DNA Repair and Recombination Protein: A DNA-binding protein that mediates DNA REPAIR of double strand breaks, and HOMOLOGOUS RECOMBINATION.DNA-(Apurinic or Apyrimidinic Site) Lyase: 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 Pigmentosum: A rare, pigmentary, and atrophic autosomal recessive disease. It is manifested as an extreme photosensitivity to ULTRAVIOLET RAYS as the result of a deficiency in the enzyme that permits excisional repair of ultraviolet-damaged DNA.DNA Helicases: 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.DNA Mismatch Repair: A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the BASE PAIR MISMATCH and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. (from Oxford Dictionary of Biochemistry and Molecular Biology, 2001)DNA: 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).Rad51 Recombinase: A Rec A recombinase found in eukaryotes. Rad51 is involved in DNA REPAIR of double-strand breaks.Xeroderma Pigmentosum Group D Protein: A DNA helicase that is a component of TRANSCRIPTION FACTOR TFIIH. It plays an essential role in NUCLEOTIDE EXCISION REPAIR, and mutations in this protein are associated with XERODERMA PIGMENTOSUM.Recombination, Genetic: 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.Endonucleases: 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.-.Xeroderma Pigmentosum Group A Protein: A ZINC FINGER MOTIF protein that recognizes and interacts with damaged DNA. It is a DNA-binding protein that plays an essential role in NUCLEOTIDE EXCISION REPAIR. Mutations in this protein are associated with the most severe form of XERODERMA PIGMENTOSUM.DNA End-Joining Repair: The repair of DOUBLE-STRAND DNA BREAKS by rejoining the broken ends of DNA to each other directly.Mutation: 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.Endodeoxyribonucleases: 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.-.Pyrimidine Dimers: Dimers found in DNA chains damaged by ULTRAVIOLET RAYS. They consist of two adjacent PYRIMIDINE NUCLEOTIDES, usually THYMINE nucleotides, in which the pyrimidine residues are covalently joined by a cyclobutane ring. These dimers block DNA REPLICATION.Methyl Methanesulfonate: An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA.O(6)-Methylguanine-DNA Methyltransferase: An enzyme that transfers methyl groups from O(6)-methylguanine, and other methylated moieties of DNA, to a cysteine residue in itself, thus repairing alkylated DNA in a single-step reaction. EC Assay: 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.Nuclear Proteins: 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.DNA Replication: The process by which a DNA molecule is duplicated.Radiation Tolerance: 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.Genomic Instability: An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.N-Glycosyl Hydrolases: A class of enzymes involved in the hydrolysis of the N-glycosidic bond of nitrogen-linked sugars.Gamma Rays: 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.Antigens, Nuclear: Immunologically detectable substances found in the CELL NUCLEUS.Poly(ADP-ribose) Polymerases: 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.Molecular Sequence Data: 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.DNA Ligases: 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 (ATP) and EC (NAD).Cell Cycle Proteins: 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.Base Pair Mismatch: The presence of an uncomplimentary base in double-stranded DNA caused by spontaneous deamination of cytosine or adenine, mismatching during homologous recombination, or errors in DNA replication. Multiple, sequential base pair mismatches lead to formation of heteroduplex DNA; (NUCLEIC ACID HETERODUPLEXES).Mutagens: 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.DNA Repair-Deficiency Disorders: Disorders resulting from defective DNA REPAIR processes or the associated cellular responses to DNA DAMAGE.Dose-Response Relationship, Radiation: The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation.Homologous Recombination: An exchange of DNA between matching or similar sequences.GuanineDeoxyribodipyrimidine Photo-Lyase: An enzyme that catalyzes the reactivation by light of UV-irradiated DNA. It breaks two carbon-carbon bonds in PYRIMIDINE DIMERS in DNA.Exodeoxyribonucleases: 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.Radiation, Ionizing: 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.Alkylating Agents: 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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Ataxia Telangiectasia Mutated Proteins: 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.Saccharomyces cerevisiae Proteins: 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.DNA-Activated Protein Kinase: 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.Saccharomyces cerevisiae: 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.DNA Breaks, Single-Stranded: Interruptions in one of the strands of the sugar-phosphate backbone of double-stranded DNA.Cell Cycle: 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.DNA Adducts: The products of chemical reactions that result in the addition of extraneous chemical groups to DNA.Aortic Aneurysm, Abdominal: An abnormal balloon- or sac-like dilatation in the wall of the ABDOMINAL AORTA which gives rise to the visceral, the parietal, and the terminal (iliac) branches below the aortic hiatus at the diaphragm.Deoxyribonuclease (Pyrimidine Dimer): An enzyme which catalyzes an endonucleolytic cleavage near PYRIMIDINE DIMERS to produce a 5'-phosphate product. The enzyme acts on the damaged DNA strand, from the 5' side of the damaged site.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Escherichia coli: 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.Histones: 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.Uracil-DNA Glycosidase: An enzyme that catalyzes the HYDROLYSIS of the N-glycosidic bond between sugar phosphate backbone and URACIL residue during DNA synthesis.Deoxyribonuclease IV (Phage T4-Induced): An enzyme which catalyzes the endonucleolytic cleavage of phosphodiester bonds at purinic or apyrimidinic sites (AP-sites) to produce 5'-Phosphooligonucleotide end products. The enzyme prefers single-stranded DNA (ssDNA) and was formerly classified as EC Syndrome: A syndrome characterized by multiple system abnormalities including DWARFISM; PHOTOSENSITIVITY DISORDERS; PREMATURE AGING; and HEARING LOSS. It is caused by mutations of a number of autosomal recessive genes encoding proteins that involve transcriptional-coupled DNA REPAIR processes. Cockayne syndrome is classified by the severity and age of onset. Type I (classical; CSA) is early childhood onset in the second year of life; type II (congenital; CSB) is early onset at birth with severe symptoms; type III (xeroderma pigmentosum; XP) is late childhood onset with mild symptoms.BRCA1 Protein: 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)Proliferating Cell Nuclear Antigen: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.HeLa Cells: 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.DNA Breaks: Interruptions in the sugar-phosphate backbone of DNA.DNA Polymerase beta: A DNA repair enzyme that catalyzes DNA synthesis during base excision DNA repair. EC Healing: Restoration of integrity to traumatized tissue.Carbon-Oxygen Lyases: Enzymes that catalyze the cleavage of a carbon-oxygen bond by means other than hydrolysis or oxidation. EC 4.2.Acetoxyacetylaminofluorene: An alkylating agent that forms DNA ADDUCTS at the C-8 position in GUANINE, resulting in single strand breaks. It has demonstrated carcinogenic action.Cell Survival: 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.Transcription Factor TFIIH: A general transcription factor that is involved in basal GENETIC TRANSCRIPTION and NUCLEOTIDE EXCISION REPAIR. It consists of nine subunits including ATP-DEPENDENT DNA HELICASES; CYCLIN H; and XERODERMA PIGMENTOSUM GROUP D PROTEIN.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Amino Acid Sequence: 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.Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.Replication Protein A: A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.Blood Vessel Prosthesis Implantation: Surgical insertion of BLOOD VESSEL PROSTHESES to repair injured or diseased blood vessels.Methylnitronitrosoguanidine: A nitrosoguanidine derivative with potent mutagenic and carcinogenic properties.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.DNA, Fungal: Deoxyribonucleic acid that makes up the genetic material of fungi.Tumor Suppressor Proteins: 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.4-Nitroquinoline-1-oxide: A potent mutagen and carcinogen. This compound and its metabolite 4-HYDROXYAMINOQUINOLINE-1-OXIDE bind to nucleic acids. It inactivates bacteria but not bacteriophage.Fanconi Anemia: Congenital disorder affecting all bone marrow elements, resulting in ANEMIA; LEUKOPENIA; and THROMBOPENIA, and associated with cardiac, renal, and limb malformations as well as dermal pigmentary changes. Spontaneous CHROMOSOME BREAKAGE is a feature of this disease along with predisposition to LEUKEMIA. There are at least 7 complementation groups in Fanconi anemia: FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, and FANCL. (from Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227650, August 20, 2004)Tumor Suppressor Protein p53: 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.Protein Binding: 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.Adenosine Triphosphatases: A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Rec A Recombinases: 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.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.MutS Homolog 2 Protein: MutS homolog 2 protein is found throughout eukaryotes and is a homolog of the MUTS DNA MISMATCH-BINDING PROTEIN. It plays an essential role in meiotic RECOMBINATION and DNA REPAIR of mismatched NUCLEOTIDES.DNA, Single-Stranded: A single chain of deoxyribonucleotides that occurs in some bacteria and viruses. It usually exists as a covalently closed circle.Chromatin: 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.Cell Line, Tumor: A cell line derived from cultured tumor cells.SOS Response (Genetics): 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.RecQ Helicases: 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.Alkylation: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group.Trichothiodystrophy Syndromes: Autosomal recessive neuroectodermal disorders characterized by brittle sulfur-deficient hair associated with impaired intellect, decreased fertility, and short stature. It may include nail dystrophy, ICHTHYOSIS, and photosensitivity correlated with a NUCLEOTIDE EXCISION REPAIR defect. All individuals with this disorder have a deficiency of cysteine-rich KERATIN-ASSOCIATED PROTEINS found in the interfilamentous matrix. Photosensitive trichothiodystrophy can be caused by mutation in at least 2 separate genes: ERCC2 PROTEIN gene and the related ERCC3. Nonphotosensitive trichothiodystrophy can be caused by mutation in the TTDN1 gene.Apoptosis: 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.Cells, Cultured: 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.Mitomycin: 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.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Cell Nucleus: 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)Fanconi Anemia Complementation Group Proteins: A diverse group of proteins whose genetic MUTATIONS have been associated with the chromosomal instability syndrome FANCONI ANEMIA. Many of these proteins play important roles in protecting CELLS against OXIDATIVE STRESS.DNA-Directed DNA Polymerase: 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.X-Rays: 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.Fungal Proteins: Proteins found in any species of fungus.DNA-Formamidopyrimidine Glycosylase: A DNA repair enzyme that is an N-glycosyl hydrolase with specificity for DNA-containing ring-opened N(7)-methylguanine residues.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.Fanconi Anemia Complementation Group D2 Protein: A Fanconi anemia complementation group protein that undergoes mono-ubiquitination by FANCL PROTEIN in response to DNA DAMAGE. Also, in response to IONIZING RADIATION it can undergo PHOSPHORYLATION by ataxia telangiectasia mutated protein. Modified FANCD2 interacts with BRCA2 PROTEIN in a stable complex with CHROMATIN, and it is involved in DNA REPAIR by homologous RECOMBINATION.MutS DNA Mismatch-Binding Protein: A methyl-directed mismatch DNA REPAIR protein that has weak ATPASE activity. MutS was originally described in ESCHERICHIA COLI.Sister Chromatid Exchange: 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.Suture Techniques: Techniques for securing together the edges of a wound, with loops of thread or similar materials (SUTURES).Models, Biological: 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.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.Plasmids: 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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.Polymorphism, Genetic: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.Hernia, Inguinal: An abdominal hernia with an external bulge in the GROIN region. It can be classified by the location of herniation. Indirect inguinal hernias occur through the internal inguinal ring. Direct inguinal hernias occur through defects in the ABDOMINAL WALL (transversalis fascia) in Hesselbach's triangle. The former type is commonly seen in children and young adults; the latter in adults.Genetic Complementation Test: A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.Checkpoint Kinase 2: 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.Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.BRCA2 Protein: 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)Poly Adenosine Diphosphate Ribose: A polynucleotide formed from the ADP-RIBOSE moiety of nicotinamide-adenine dinucleotide (NAD) by POLY(ADP-RIBOSE) POLYMERASES.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Exonucleases: Enzymes that catalyze the release of mononucleotides by the hydrolysis of the terminal bond of deoxyribonucleotide or ribonucleotide chains.Models, Genetic: 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.Protein Structure, Tertiary: 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.UracilFlap Endonucleases: 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.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Deoxyguanosine: A nucleoside consisting of the base guanine and the sugar deoxyribose.Aortic Rupture: The tearing or bursting of the wall along any portion of the AORTA, such as thoracic or abdominal. It may result from the rupture of an aneurysm or it may be due to TRAUMA.Bacterial Proteins: Proteins found in any species of bacterium.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Antineoplastic Agents, Alkylating: A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026)Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.Chromosomal Proteins, Non-Histone: 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.DNA, Neoplasm: DNA present in neoplastic tissue.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Gene Deletion: 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.G2 Phase: 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.Aortic Aneurysm, Thoracic: An abnormal balloon- or sac-like dilatation in the wall of the THORACIC AORTA. This proximal descending portion of aorta gives rise to the visceral and the parietal branches above the aortic hiatus at the diaphragm.Signal Transduction: 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.Methyltransferases: A subclass of enzymes of the transferase class that catalyze the transfer of a methyl group from one compound to another. (Dorland, 28th ed) EC 2.1.1.Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.Chromatin Assembly and Disassembly: The mechanisms effecting establishment, maintenance, and modification of that specific physical conformation of CHROMATIN determining the transcriptional accessibility or inaccessibility of the DNA.Blood Vessel Prosthesis: Device constructed of either synthetic or biological material that is used for the repair of injured or diseased blood vessels.Telomere: 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.Kinetics: The rate dynamics in chemical or physical systems.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Schizosaccharomyces pombe Proteins: 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.Deinococcus: A genus of gram-positive aerobic cocci found in the soil, that is highly resistant to radiation, especially ionizing radiation (RADIATION, IONIZING). Deinococcus radiodurans is the type species.Ubiquitin-Conjugating Enzymes: A class of enzymes that form a thioester bond to UBIQUITIN with the assistance of UBIQUITIN-ACTIVATING ENZYMES. They transfer ubiquitin to the LYSINE of a substrate protein with the assistance of UBIQUITIN-PROTEIN LIGASES.Aging, Premature: Changes in the organism associated with senescence, occurring at an accelerated rate.Genes, Fungal: The functional hereditary units of FUNGI.Cross-Linking Reagents: 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.Ataxia Telangiectasia: 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).Polynucleotide 5'-Hydroxyl-Kinase: An enzyme that catalyzes the transfer of a phosphate group to the 5'-terminal hydroxyl groups of DNA and RNA. EC Radiographic visualization of the aorta and its branches by injection of contrast media, using percutaneous puncture or catheterization procedures.7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide: 7,8,8a,9a-Tetrahydrobenzo(10,11)chryseno (3,4-b)oxirene-7,8-diol. A benzopyrene derivative with carcinogenic and mutagenic activity.Nucleic Acid Heteroduplexes: Double-stranded nucleic acid molecules (DNA-DNA or DNA-RNA) which contain regions of nucleotide mismatches (non-complementary). In vivo, these heteroduplexes can result from mutation or genetic recombination; in vitro, they are formed by nucleic acid hybridization. Electron microscopic analysis of the resulting heteroduplexes facilitates the mapping of regions of base sequence homology of nucleic acids.Carcinogens: Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.DNA Primers: 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.Herniorrhaphy: Surgical procedures undertaken to repair abnormal openings through which tissue or parts of organs can protrude or are already protruding.Ficusin: A naturally occurring furocoumarin, found in PSORALEA. After photoactivation with UV radiation, it binds DNA via single and double-stranded cross-linking.Schizosaccharomyces: A genus of ascomycetous fungi of the family Schizosaccharomycetaceae, order Schizosaccharomycetales.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Chromosome Breakage: A type of chromosomal aberration involving DNA BREAKS. Chromosome breakage can result in CHROMOSOMAL TRANSLOCATION; CHROMOSOME INVERSION; or SEQUENCE DELETION.Vascular Surgical Procedures: Operative procedures for the treatment of vascular disorders.Endovascular Procedures: Minimally invasive procedures, diagnostic or therapeutic, performed within the BLOOD VESSELS. They may be perfomed via ANGIOSCOPY; INTERVENTIONAL MAGNETIC RESONANCE IMAGING; INTERVENTIONAL RADIOGRAPHY; or INTERVENTIONAL ULTRASONOGRAPHY.ThymineSubstrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Blotting, Western: 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.Postoperative Complications: Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Hair Diseases: Diseases affecting the orderly growth and persistence of hair.Cell Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances.Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.S Phase: 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.Chromosome Aberrations: Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.Chromatids: 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)Radiation-Sensitizing Agents: Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Lymphocytes: 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.Oligonucleotides: 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)DNA Modification Methylases: Enzymes that are part of the restriction-modification systems. They are responsible for producing a species-characteristic methylation pattern, on either adenine or cytosine residues, in a specific short base sequence in the host cell's own DNA. This methylated sequence will occur many times in the host-cell DNA and remain intact for the lifetime of the cell. Any DNA from another species which gains entry into a living cell and lacks the characteristic methylation pattern will be recognized by the restriction endonucleases of similar specificity and destroyed by cleavage. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Mutagenicity Tests: Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Bleomycin: 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.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Cricetulus: 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.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Mice, Knockout: 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.CHO Cells: 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.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Genes, cdc: 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).

Drosophila oogenesis: versatile spn doctors. (1/14812)

Recent work on Drosophila oogenesis has uncovered connections between cell-cycle checkpoints and pattern formation. Genes of the spindle class, which encode double-strand break repair enzymes and RNA helicases, affect oocyte polarity and the decision whether to differentiate as an oocyte or a nurse cell.  (+info)

Accelerated accumulation of somatic mutations in mice deficient in the nucleotide excision repair gene XPA. (2/14812)

Inheritable mutations in nucleotide excision repair (NER) genes cause cancer-prone human disorders, such as xeroderma pigmentosum, which are also characterized by symptoms of accelerated ageing. To study the impact of NER deficiency on mutation accumulation in vivo, mutant frequencies have been determined in liver and brain of 2-16 month old NER deficient XPA-/-, lacZ hybrid mice. While mutant frequencies in liver of 2-month old XPA-/-, lacZ mice were comparable to XPA+/-, lacZ and the lacZ parental strain animals, by 4 months of age mutant frequencies in the XPA-deficient mice were significantly increased by a factor of two and increased further until the age of 16 months. In brain, mutant frequencies were not found to increase with age. These results show that a deficiency in the NER gene XPA causes an accelerated accumulation of somatic mutations in liver but not in brain. This is in keeping with a higher incidence of spontaneous liver tumors reported earlier for XPA-/- mice after about 15 months of age.  (+info)

The Saccharomyces cerevisiae ETH1 gene, an inducible homolog of exonuclease III that provides resistance to DNA-damaging agents and limits spontaneous mutagenesis. (3/14812)

The recently sequenced Saccharomyces cerevisiae genome was searched for a gene with homology to the gene encoding the major human AP endonuclease, a component of the highly conserved DNA base excision repair pathway. An open reading frame was found to encode a putative protein (34% identical to the Schizosaccharomyces pombe eth1(+) [open reading frame SPBC3D6.10] gene product) with a 347-residue segment homologous to the exonuclease III family of AP endonucleases. Synthesis of mRNA from ETH1 in wild-type cells was induced sixfold relative to that in untreated cells after exposure to the alkylating agent methyl methanesulfonate (MMS). To investigate the function of ETH1, deletions of the open reading frame were made in a wild-type strain and a strain deficient in the known yeast AP endonuclease encoded by APN1. eth1 strains were not more sensitive to killing by MMS, hydrogen peroxide, or phleomycin D1, whereas apn1 strains were approximately 3-fold more sensitive to MMS and approximately 10-fold more sensitive to hydrogen peroxide than was the wild type. Double-mutant strains (apn1 eth1) were approximately 15-fold more sensitive to MMS and approximately 2- to 3-fold more sensitive to hydrogen peroxide and phleomycin D1 than were apn1 strains. Elimination of ETH1 in apn1 strains also increased spontaneous mutation rates 9- or 31-fold compared to the wild type as determined by reversion to adenine or lysine prototrophy, respectively. Transformation of apn1 eth1 cells with an expression vector containing ETH1 reversed the hypersensitivity to MMS and limited the rate of spontaneous mutagenesis. Expression of ETH1 in a dut-1 xthA3 Escherichia coli strain demonstrated that the gene product functionally complements the missing AP endonuclease activity. Thus, in apn1 cells where the major AP endonuclease activity is missing, ETH1 offers an alternate capacity for repair of spontaneous or induced damage to DNA that is normally repaired by Apn1 protein.  (+info)

The 3'-->5' exonucleases of DNA polymerases delta and epsilon and the 5'-->3' exonuclease Exo1 have major roles in postreplication mutation avoidance in Saccharomyces cerevisiae. (4/14812)

Replication fidelity is controlled by DNA polymerase proofreading and postreplication mismatch repair. We have genetically characterized the roles of the 5'-->3' Exo1 and the 3'-->5' DNA polymerase exonucleases in mismatch repair in the yeast Saccharomyces cerevisiae by using various genetic backgrounds and highly sensitive mutation detection systems that are based on long and short homonucleotide runs. Genetic interactions were examined among DNA polymerase epsilon (pol2-4) and delta (pol3-01) mutants defective in 3'-->5' proofreading exonuclease, mutants defective in the 5'-->3' exonuclease Exo1, and mismatch repair mutants (msh2, msh3, or msh6). These three exonucleases play an important role in mutation avoidance. Surprisingly, the mutation rate in an exo1 pol3-01 mutant was comparable to that in an msh2 pol3-01 mutant, suggesting that they participate directly in postreplication mismatch repair as well as in other DNA metabolic processes.  (+info)

Postnatal growth failure, short life span, and early onset of cellular senescence and subsequent immortalization in mice lacking the xeroderma pigmentosum group G gene. (5/14812)

The xeroderma pigmentosum group G (XP-G) gene (XPG) encodes a structure-specific DNA endonuclease that functions in nucleotide excision repair (NER). XP-G patients show various symptoms, ranging from mild cutaneous abnormalities to severe dermatological impairments. In some cases, patients exhibit growth failure and life-shortening and neurological dysfunctions, which are characteristics of Cockayne syndrome (CS). The known XPG protein function as the 3' nuclease in NER, however, cannot explain the development of CS in certain XP-G patients. To gain an insight into the functions of the XPG protein, we have generated and examined mice lacking xpg (the mouse counterpart of the human XPG gene) alleles. The xpg-deficient mice exhibited postnatal growth failure and underwent premature death. Since XPA-deficient mice, which are totally defective in NER, do not show such symptoms, our data indicate that XPG performs an additional function(s) besides its role in NER. Our in vitro studies showed that primary embryonic fibroblasts isolated from the xpg-deficient mice underwent premature senescence and exhibited the early onset of immortalization and accumulation of p53.  (+info)

Analysis of genomic integrity and p53-dependent G1 checkpoint in telomerase-induced extended-life-span human fibroblasts. (6/14812)

Life span determination in normal human cells may be regulated by nucleoprotein structures called telomeres, the physical ends of eukaryotic chromosomes. Telomeres have been shown to be essential for chromosome stability and function and to shorten with each cell division in normal human cells in culture and with age in vivo. Reversal of telomere shortening by the forced expression of telomerase in normal cells has been shown to elongate telomeres and extend the replicative life span (H. Vaziri and S. Benchimol, Curr. Biol. 8:279-282, 1998; A. G. Bodnar et al., Science 279:349-352, 1998). Extension of the life span as a consequence of the functional inactivation of p53 is frequently associated with loss of genomic stability. Analysis of telomerase-induced extended-life-span fibroblast (TIELF) cells by G banding and spectral karyotyping indicated that forced extension of the life span by telomerase led to the transient formation of aberrant structures, which were subsequently resolved in higher passages. However, the p53-dependent G1 checkpoint was intact as assessed by functional activation of p53 protein in response to ionizing radiation and subsequent p53-mediated induction of p21(Waf1/Cip1/Sdi1). TIELF cells were not tumorigenic and had a normal DNA strand break rejoining activity and normal radiosensitivity in response to ionizing radiation.  (+info)

Phosphorylation of the DNA repair protein APE/REF-1 by CKII affects redox regulation of AP-1. (7/14812)

The DNA repair protein apurinic endonuclease (APE/Ref-1) exerts several physiological functions such as cleavage of apurinic/apyrimidinic sites and redox regulation of the transcription factor AP-1, whose activation is part of the cellular response to DNA damaging treatments. Here we demonstrate that APE/Ref-1 is phosphorylated by casein kinase II (CKII). This was shown for both the recombinant APE/Ref-1 protein (Km=0.55 mM) and for APE/Ref-1 expressed in COS cells. Phosphorylation of APE/Ref-1 did not alter the repair activity of the enzyme, whereas it stimulated its redox capability towards AP-1, thus promoting DNA binding activity of AP-1. Inhibition of CKII mediated phosphorylation of APE/Ref-1 blocked mutagen-stimulated increase in AP-1 binding. It also abrogated the induction of c-Jun protein and rendered cells more sensitive to induced DNA damage. Thus, phosphorylation of APE/Ref-1 appears to be involved in regulating the different physiological activities of the enzyme. CKII mediated phosphorylation of APE/Ref-1 and concomitant increase in AP-1 binding activity appears to be a novel mechanism of cellular stress response, forcing transcription of AP-1 target gene(s) the product(s) of which may exert protective function.  (+info)

Differential regulation of p21waf-1/cip-1 and Mdm2 by etoposide: etoposide inhibits the p53-Mdm2 autoregulatory feedback loop. (8/14812)

The Mdm2 protein is frequently overexpressed in human non-seminomatous germ cell tumours and transitional carcinoma of the bladder where it may contribute to tolerance of wtp53. Mdm2 forms an autoregulatory feedback loop with p53; the Mdm2 gene is responsive to transactivation by p53 and once synthesized the Mdm2 protein terminates the p53 response. We show here that the topoisomerase poison etoposide, like ultra violet irradiation, inhibits Mdm2 synthesis. Cytotoxic concentrations of etoposide (IC90 for > 3 h) result in inhibition of Mdm2 induction at both the RNA and protein level. Rapid apoptosis ensues. Global transcription is not inhibited: p21waf-1/cip1 and GADD45 expression increase in a dose dependent manner. Inhibition of Mdm2 synthesis depends on the continuous presence of etoposide, suggesting the DNA damage may prevent transcription. Downregulation of Mdm2 transcript occurs in cells expressing HPV16-E6 suggesting that inhibition of Mdm2 transcription is p53-independent. When cells are -treated with a pulse (1 h) of etoposide and reincubated in drug free medium, Mdm2 synthesis commences immediately after damage is repaired (3 h) and the p53 response is attenuated. Induction of apoptosis and loss of clonogenicity are 3-5-fold lower under pulse treatment conditions. This is the first observation of inhibition of Mdm2 transcription following treatment with topoisomerase (topo II) poisons, a feature that may be useful in tumour types where p53 is tolerated by overexpression of Mdm2.  (+info)

The rates at which lesions are removed by DNA repair can vary widely throughout the genome, with important implications for genomic stability. To study this, we measured the distribution of nucleotide excision repair (NER) rates for UV-induced lesions throughout the budding yeast genome. By plotting these repair rates in relation to genes and their associated flanking sequences, we reveal that, in normal cells, genomic repair rates display a distinctive pattern, suggesting that DNA repair is highly organized within the genome. Furthermore, by comparing genome-wide DNA repair rates in wild-type cells and cells defective in the global genome-NER (GG-NER) subpathway, we establish how this alters the distribution of NER rates throughout the genome. We also examined the genomic locations of GG-NER factor binding to chromatin before and after UV irradiation, revealing that GG-NER is organized and initiated from specific genomic locations. At these sites, chromatin occupancy of the histone ...
To investigate how the nucleotide excision repair initiator XPC locates DNA damage in mammalian cell nuclei we analyzed the dynamics of GFP-tagged XPC. Photobleaching experiments showed that XPC constantly associates with and dissociates from chromatin in the absence of DNA damage. DNA-damaging agents retard the mobility of XPC, and UV damage has the most pronounced effect on the mobility of XPC-GFP. XPC exhibited a surprising distinct dynamic behavior and subnuclear distribution compared with other NER factors. Moreover, we uncovered a novel regulatory mechanism for XPC. Under unchallenged conditions, XPC is continuously exported from and imported into the nucleus, which is impeded when NER lesions are present. XPC is omnipresent in the nucleus, allowing a quick response to genotoxic stress. To avoid excessive DNA probing by the low specificity of the protein, the steady-state level in the nucleus is controlled by nucleus-cytoplasm shuttling, allowing temporally higher concentrations of XPC in ...
Marian Blanca Ramírez from the CSIC in Spain has been studying the effects of LRRK2, a protein associated with Parkinsons disease, on cell motility. A Travelling Fellowship from Journal of Cell Science allowed her to spend time in Prof Maddy Parsons lab at Kings College London, learning new cell migration assays and analysing fibroblasts cultured from individuals with Parkinsons. Read more on her story here. Where could your research take you? The deadline to apply for the current round of Travelling Fellowships is 23rd Feburary 2018. Apply now!. ...
It has been suggested that phosphorylation of the histone variant H2AX after ultraviolet light (UV) irradiation is triggered by DNA double-strand breaks induced as replication forks collide with UV-induced bulky lesions. More recently, it has been shown that UV-induced H2AX phosphorylation can also occur outside of S-phase, but the mechanism for this replication-independent induction is not well understood. In this study, we show that H2AX phosphorylation after UV irradiation is triggered by DNA repair intermediates and is induced in all phases of the cell cycle. Accumulation of DNA repair intermediates by inhibition of DNA repair synthesis resulted in a marked increase of H2AX phosphorylation in repair proficient but not repair-deficient xeroderma pigmentosum-A cells. Using chemical inhibitors of the PI(3)-like kinase family of protein kinases as well as ataxia telangiectasia mutated and Rad-3 related (ATR)-deficient Seckel syndrome cells and ataxia telangiectasia mutated-deficient ataxia ...
The expression of chloramphenicol acetyl transferase (CAT) as reporter can be detected in a variety of ways and has been the reporter of choice in reporter-vector systems for long time [20]. However, the notable disadvantage of these systems, however, is that the expressed reporter protein must be assayed via enzymatic reactions using whole cell extracts into which the reporter vector has been transfected [21].. Furthermore the quantification of DNA repair capacity via protein expression is disadvantageous because cells normally take up more than one plasmid, and therefore it is not possible to quantify the number of cells that are able to repair. With a view to the development of (skin-) malignancies, we also have to address the question whether a decrease in DNA repair capacity of a cell population rests on complete repair deficiency of single cells (while others remained unaffected) or on a partial decrease of DNA repair capacity in all cells. In our view single, repair deficient cells ...
TY - JOUR. T1 - E2F1 regulates the base excision repair gene XRCC1 and promotes DNA repair. AU - Chen, Dexi. AU - Yu, Zhiyong. AU - Zhu, Zhiyi. AU - Lopez, Charles D.. PY - 2008/5/30. Y1 - 2008/5/30. N2 - The E2F1 transcription factor activates S-phase-promoting genes, mediates apoptosis, and stimulates DNA repair through incompletely understood mechanisms. XRCC1 (x-ray repair cross-complementing group 1) protein is important for efficient single strand break/base excision repair. Although both damage and proliferative signals increase XRCC1 levels, the mechanisms regulating XRCC1 transcription remain unclear. To study these upstream mechanisms, the XRCC1 promoter was cloned into a luciferase reporter. Ectopic expression of wild-type E2F1, but not an inactive mutant E2F1(132E), activated the XRCC1 promoter-luciferase reporter, and deletion of predicted E2F1 binding sites in the promoter attenuated E2F1-induced activation. Endogenous XRCC1 expression increased in cells conditionally expressing ...
DNA repair plays a key role in carcinogenesis through the removal and repair of DNA damage induced by endogenous and environmental sources. The DNA repair system included four pathways: 1) Base Excision Repair (BER), 2) Nucleotide Excision Repair (NER), 3) Mismatch Repair (MMR) and 4) Double-Strand Break Repair, including homologous recombination pathway and nonhomologous end-joining repair pathway. Decreased and impaired DNA repair capacity has been reported in various cancers, however, its effect on prostate cancer still under investigated.. Common polymorphisms in DNA repair gene may alter protein function and individuals capacity to repair damaged DNA, hence, influence the cancer susceptibility. Polymorphic variants of DNA repair gene have been found to be associated with cancer susceptibility, but rare studies have investigated their effect on prostate cancer. Since variation in the function of these DNA repair genes also impact a cancer cells viability or resistance to treatment, genetic ...
Somatic mutations in cancer are more frequent in heterochromatic and late-replicating regions of the genome. We report that regional disparities in mutation density are virtually abolished within transcriptionally silent genomic regions of cutaneous squamous cell carcinomas (cSCCs) arising in an XPC(-/-) background. XPC(-/-) cells lack global genome nucleotide excision repair (GG-NER), thus establishing differential access of DNA repair machinery within chromatin-rich regions of the genome as the primary cause for the regional disparity. Strikingly, we find that increasing levels of transcription reduce mutation prevalence on both strands of gene bodies embedded within H3K9me3-dense regions, and only to those levels observed in H3K9me3-sparse regions, also in an XPC-dependent manner. Therefore, transcription appears to reduce mutation prevalence specifically by relieving the constraints imposed by chromatin structure on DNA repair. We model this relationship among transcription, chromatin state, and DNA
The purpose of this study was to elucidate if the cellular DNA repair capacity, genotypes of DNA repair genes and the occurrence of breast cancer can be associated with each other on the same set of probands in a single study. Rarely characterized features of the DNA repair capacity measures were studied as a prerequisite for their use in the definition as an intermediate phenotype of cancer. The study population comprised different cohorts with sporadic or familial breast cancer cases and controls. DNA repair assays were performed in parallel on peripheral blood samples of the probands: the baseline and the radiation induced micronucleus (MN) assay, the baseline and the induced sister chromatid exchange (SCE) assay and the mitotic delay (MD) assay. 23 missense variants in 15 genes were genotyped. An increased induced MN frequency and a decreased MD index were associated with the occurrence of breast cancer. The minor allele of the variant Slx4 S1271F (rs3810813) was enriched in breast cancer ...
Oxidized DNA base lesions, such as thymine glycol (Tg) and 8-hydroxyguanine, are often toxic and mutagenic and have been implicated in carcinogenesis. To clarify whether NEIL1 protein, which exhibits excision repair activity towards such base lesions, is involved in gastric carcinogenesis, we examined 71 primary gastric cancers from Japanese patients and four gastric cancer cell lines for mutations and genetic polymorphisms of the NEIL1 gene. We also examined 20 blood samples from Chinese patients for NEIL1 genetic polymorphisms. Three mutations (c.82_84delGAG:p.Glu28del, c.936G , A and c.1000A , G:p.Arg334Gly) and two genetic polymorphisms were identified. When the excision repair activity towards double-stranded oligonucleotide containing a Tg:A base pair was compared among six types of recombinant NEIL1 proteins, p.Glu28del-type NEIL1, found in a primary case, was found to exhibit an extremely low activity level. Moreover, c.936G , A, located in the last nucleotide of exon 10 and detected in ...
Elliott, R, Astley, S, Southon, S and Archer, D (2000) The development of DNA repair assays which show that dietary carrots stimulate DNA repair activity In: 3rd Conference on Food and Cancer Prevention, 1999-09-05 - 1999-09-08, UNIV E ANGLIA, NORWICH, ENGLAND. Full text not available from this repository ...
DNA repair capacity varies greatly between individuals, and evidence has begun to link this variation to cancer risk, obesity and related chronic diseases. There is also emerging evidence that dietary components can affect DNA repair, but research to date has been restricted by methods for measuring DNA repair. This study made use of newly developed microplate-based assays for the direct determination of DNA repair enzyme activities. Lipid loading of the HepG2 human hepatocellular carcinoma cell line was employed as a model to test the hypothesis that hepatic steatosis affects DNA repair activity via induction of oxidative stress.. ...
Purpose: DNA repair deficiencies have been postulated to play a role in the development and progression of cardiovascular disease (CVD). The hypothesis is that DNA damage may induce cell death that promotes formation of unstable plaques. Defects in the DNA repair mechanisms may therefore increase the risk of cardiovascular events. Using a DNA repair pathway approach we systematically examined whether common genetic variation in DNA repair genes influence the risk of cardiovascular disease progression and cardiovascular events.. Methods: DNA repair genes were selected using a systematic pathway approach and a total of 59 single nucleotide polymorphisms (SNPs) within 24 genes were selected using several criteria such as adequate heterogeneity, LD pattern and validation status. Eleven additional SNPs from literature were added. Genotyping was performed using Illumina Human 660-Quad Beadchips in 5244 subject of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. Collected ...
TY - JOUR. T1 - Polymorphisms in DNA repair genes, smoking, and pancreatic adenocarcinoma risk. AU - Mc Williams, Robert R. AU - Bamlet, William R.. AU - Cunningham, Julie M. AU - Goode, Ellen L. AU - De Andrade, Mariza. AU - Boardman, Lisa Allyn. AU - Petersen, Gloria M. PY - 2008/6/15. Y1 - 2008/6/15. N2 - Base excision repair and nucleotide excision repair are vital responses to multiple types of DNA damage, including damage from tobacco exposure. Single-nucleotide polymorphisms (SNP)in these pathways may affect DNA repair capacity and therefore influence risk for cancer development. We performed a clinic-based, case-control study comprising 481 consecutive patients with confirmed pancreatic adenocarcinoma and 625 healthy controls. Allele and genotype frequencies for 16 SNPs in DNA repair genes ERCC1, XPD/ERCC2, XPC, XPF/ERCC4, OGG1, and XRCC1 were compared after adjusting for age, sex, and smoking history. Subgroup analysis by sex and smoking history was performed. Carriers of one or two ...
Nucleotide excision repair (NER) is a major DNA repair pathway in eukaryotic cells. NER removes structurally diverse lesions such as pyrimidine dimers, arising upon UV irradiation or bulky chemical adducts, arising upon exposure to carcinogens and some chemotherapeutic drugs. NER defects lead to three genetic disorders that result in predisposition to cancers, accelerated aging, neurological and developmental defects. During NER, more than 30 polypeptides cooperate to recognize, incise, and excise a damaged oligonucleotide from the genomic DNA. Recent papers reveal an additional and unexpected role for the NER factors. In the absence of a genotoxic attack, the promoters of RNA polymerases I- and II-dependent genes recruit XPA, XPC, XPG, and XPF to initiate gene expression. A model that includes the growth arrest and DNA damage 45alpha protein (Gadd45alpha) and the NER factors, in order to maintain the promoter of active genes under a hypomethylated state, has been proposed but remains controversial.
The researchers found that single mismatched ribonucleotides in chromosomal DNA were removed by either the mismatch repair system or RNase H type 2. Mismatched ribonucleotides in the middle of at least four other ribonucleotides required RNase H type 1 for removal.. "We were excited to find that a DNA repair mechanism like mismatch repair was activated by RNA/DNA mismatches and could remove ribonucleotides embedded in chromosomal DNA," explained Storici. "In future studies, we plan to test whether other DNA repair mechanisms, such as nucleotide-excision repair and base-excision repair, can also locate and remove ribonucleotides in DNA.". Using gene correction assays driven by short nucleic acid polymers called oligonucleotides, the researchers showed that when ribonucleotides embedded in DNA were not removed, they served as templates for DNA synthesis and produced a mutation in the DNA. If both the mismatch repair system and RNase H repair mechanisms are disabled, ribonucleotide-driven gene ...
Base excision repair (BER) is the predominant DNA damage repair pathway for the processing of small base lesions, derived from oxidation and alkylation damages. BER is normally defined as DNA repair initiated by lesion-specific DNA glycosylases and completed by either of the two sub-pathways: short-patch BER where only one nucleotide is replaced and long-patch BER where 2-13 nucleotides are replaced. Each sub-pathway of BER relies on the formation of protein complexes that assemble at the site of the DNA lesion and facilitate repair in a coordinated fashion. This process of complex formation appears to provide an increase in specificity and efficiency to the BER pathway, thereby facilitating the maintenance of genome integrity by preventing the accumulation of highly toxic repair intermediates ...
Base excision repair (BER) is the predominant DNA damage repair pathway for the processing of small base lesions, derived from oxidation and alkylation damages. BER is normally defined as DNA repair initiated by lesion-specific DNA glycosylases and completed by either of the two sub-pathways: short-patch BER where only one nucleotide is replaced and long-patch BER where 2-13 nucleotides are replaced. Each sub-pathway of BER relies on the formation of protein complexes that assemble at the site of the DNA lesion and facilitate repair in a coordinated fashion. This process of complex formation appears to provide an increase in specificity and efficiency to the BER pathway, thereby facilitating the maintenance of genome integrity by preventing the accumulation of highly toxic repair intermediates ...
The molecular etiology of breast cancer has proven to be re- markably complex. Most individual oncogenes are disregulated in only approximately 30% of breast tumors, indicating that either very few molecular alterations are common to the majority of breast cancers, or that they have not yet been identified. In striking contrast, we now show that 19 of 19 stage I breast tumors tested with the functional unscheduled DNA synthesis assay exhibited a significant deficiency of DNA nucleotide excision repair (NER) capacity relative to normal epithelial tissue from disease-free controls (n = 23). Loss of DNA repair capacity, including the complex, damage-comprehensive NER pathway, results in genomic instabil- ity, a hallmark of carcinogenesis. By microarray analysis, mRNA ex- pression levels for 20 canonical NER genes were reduced in repre- sentative tumor samples versus normal. Significant reductions were observed in 19 of these genes analyzed by the more sensitive method of RNase protection. These results
The nucleotide excision repair (NER) pathway operates through two sub-pathways: global genome repair (ggNER) and transcription-coupled repair (TCR) or gene- and strand-specific DNA repair [1, 2, 4]. The ggNER is a repair mechanism which has the ability to repair DNA damage to the overall genome with equivalent efficiency. In contrast, TCR is a kind of heterogeneous DNA repair, where repair to the damaged DNA in the status of transcription activity is superior to the silenced genes and the repair of the transcribed strand is superior to the untranscribed strand. Some DNA repair proteins and transcription factors have been identified to be involved in TCR such as CSA, CSB, XPG, XAB2, RNA polymerase II, and TFIIH [1, 7, 8, 24]. Blockage of RNA polymerase □ at the DNA damage site is believed to create a conducive environment for DNA repair [7, 9]. In this report, we provide evidence to demonstrate that DNA-PKcs, a known critical component in the NHEJ pathway of DNA double-strand breaks, is also ...
The role of nucleotide excision repair (NER) in the maintenance of DNA integrity under oxidative assault has yet to be elucidated. A defective NER can result in Xeroderma Pigmentosa (XP) or Cockayne Syndrome (CS), both autosomal recessive diseases, presenting with increased cancer risk and segmental progeria. Although the NER is characterized to be involved in repairing UV-induced damage, it is difficult to attribute all the symptoms of XP and CS to UV-damage. Oxidative stress is thus likely to be an important factor. Other DNA repair proteins including a component of the NER pathway, XPF, have been reported to be involved in telomere dynamics. As the importance of the NER pathway in removing oxidative stress-induced DNA lesions is still unclear, we sought to understand the role of NER in oxidative stress-induced damage protection and telomere-mediated chromosome integrity. In our study, we utilized primary cells derived from patients suffering from XP (XP-A and XP-D) and CS Type II (CS-B), as ...
Efficient and correct repair of DNA damage, especially DNA double-strand breaks (DSBs), is vital for the survival of individual cells and organisms. Defects in the DNA repair may lead to cell death or genomic instability and development of cancer. The repair of DSBs in cell lines with different DSB rejoining capabilities was studied after exposure to ionising radiation. A new cell lysis protocol performed at 0ºC, which prevents the inclusion of non-true DSBs in the quantification of DSBs by pulsed-field gel electrophoresis (PFGE), was developed. Results showed that when the standard protocol at 50ºC was used, 30-40% of the initial yield of DSBs corresponds to artifactual DSBs. 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.. Non-homologous end-joining (NHEJ) is the major DSB repair pathway in mammalian cells. We show that DSBs are processed into long single-stranded DNA (ssDNA) ...
In this study, we report the role of genetic polymorphisms XRCC1 Arg194Trp (C→T) and Arg399Gln (G→A), OGG1 Ser326Cys (C→G), APEX1 Asp148Glu (T→G), MUTYH Gln335His (G→C) and PARP1 Val762Ala (T→C) on the individual susceptibility for TC. The frequencies of the different genotypes observed in the control population are similar to those reported in other Caucasian populations.. XRCC1 is a nuclear protein that, despite lacking any enzymatic activity, plays an important role in the efficient repair of SSBs and in the BER pathway: it acts as a scaffold protein that facilitates the recruitment of multiple DNA repair enzymes (such as Pol β, hOGG1, APEX1, PARP1 and LIG3) to lesion sites and coordinates the DNA damage repair response. Arg194Trp and Arg399Gln are among the most extensively studied XRCC1 coding region SNPs. Both polymorphisms have been shown to alter the functional activity of the resulting protein in vitro and to interfere with cancer susceptibility: the 194Trp allele has been ...
DESCRIPTION (provided by applicant): This is an effort to relate polymorphisms in DNA repair to incidence of breast cancer. Mutations in both the BER and HRR pathways are proposed to make an individual more sensitive to ionizing radiation and breast cancer. Assays for assessing decreased activity in these pathways will also be pursued. Our long-term goal in cancer prevention is to identify high-risk populations by using DNA repair markers and to design mechanistic-based prevention strategy tailored to the specific risk profiles of individuals. Human cells are constantly exposed to exogenous and endogenous carcinogens capable of causing DNA damage. Efficient repair is critical in maintaining genome integrity and genetic variability in DNA repair may influence individuals susceptibility to cancer. Our working hypothesis is that polymorphism of DNA repair genes with nonconservative amino acid substitution may lead to altered protein function in DNA repair and elevated breast cancer risk. Various ...
DNA excision repair protein ERCC-1 is a protein that in humans is encoded by the ERCC1 gene. Together with ERCC4, ERCC1 forms the ERCC1-XPF enzyme complex that participates in DNA repair and DNA recombination. Many aspects of these two gene products are described together here because they are partners during DNA repair. The ERCC1-XPF nuclease is an essential activity in the pathway of DNA nucleotide excision repair (NER). The ERCC1-XPF nuclease also functions in pathways to repair double-strand breaks in DNA, and in the repair of "crosslink" damage that harmfully links the two DNA strands. Cells with disabling mutations in ERCC1 are more sensitive than normal to particular DNA damaging agents, including ultraviolet (UV) radiation and to chemicals that cause crosslinking between DNA strands. Genetically engineered mice with disabling mutations in ERCC1 have defects in DNA repair, accompanied by metabolic stress-induced changes in physiology that result in premature aging. Complete deletion of ...
The drug shows high potency and activity in various experimental models including P-gp- and MRP1-expressing multidrug resistant tumors as well as tumors resistant to platinum derivatives, alkylating agents and topoisomerase I and II inhibitors. Nemorubicin has a peculiar mechanism of action requiring NER activity for its full cytotoxicity. Cell lines defective in NER, which show an increased sensitivity to classical alkylating agents, display a three-four fold resistance to nemorubicin. Interestingly, L1210 murine leukemia cells selected for resistance to nemorubicin (L1210/MMDX) show a collateral sensitivity to both platinum derivatives and alkylating agents and are more sensitive (about 4-5 times) to UV light. In addition, these cells are not able to repair UV-induced damage on transfected DNA (host -cell reactivation assay), suggesting that the NER system might be involved in mediating the cytotoxic activity of nemorubicin. The aim of the present study was to evaluate the possible presence of ...
Explorers have dreamt for centuries of a Fountain of Youth, with healing waters that rejuvenate the old and extend life indefinitely.. Researchers at the University of Rochester, however, have uncovered more evidence that the key to longevity resides instead in a gene.. In a new paper published in the journal Cell, the researchers - including Vera Gorbunova and Andrei Seluanov, professors of biology; Dirk Bohmann, professor of biomedical genetics; and their team of students and postdoctoral researchers - found that the gene sirtuin 6 (SIRT6) is responsible for more efficient DNA repair in species with longer lifespans. The research illuminates new targets for anti-aging interventions and could help prevent age-related diseases.. INEVITABLE DOUBLE-STRAND BREAKS. As humans and other mammals grow older, their DNA is increasingly prone to breaks, which can lead to gene rearrangements and mutations - hallmarks of cancer and aging. For that reason, researchers have long hypothesized that DNA repair ...
Anthracyclines have been widely used as antitumor agents, playing a crucial role in the successful treatment of many types of cancer, despite some side effects related to cardiotoxicity. New anthracyclines have been designed and tested, but the first ones discovered, doxorubicin and daunorubicin, continue to be the drugs of choice. Despite their extensive use in chemotherapy, little is known about the DNA repair mechanisms involved in the removal of lesions caused by anthracyclines. the anthracycline cosmomycin D is the main product isolated from Streptomyces olindensis, characterized by a peculiar pattern of glycosylation with two trisaccharide rings attached to the A ring of the tetrahydrotetracene.We assessed the induction of apoptosis (Sub-G(1)) by cosmomycin D in nucleotide excision repair-deficient fibroblasts (XP-A and XP-C) as well as the levels of DNA damage (alkaline comet assay).Treatment of XP-A and XP-C cells with cosmomycin D resulted in apoptosis in a time-dependent manner, with ...
Eukaryotic cells deploy overlapping repair pathways to resolve DNA damage. Advancements in genome editing take advantage of these pathways to produce permanent genetic changes. Despite recent improvements, genome editing can produce diverse outcomes that can introduce risks in clinical applications. Although homology-directed repair is attractive for its ability to encode precise edits, it is particularly difficult in human cells. Here we discuss the DNA repair pathways that underlie genome editing and strategies to favour various outcomes. Harnessing DNA repair pathways in genome editing In this Review, Yeh, Richardson and Corn discuss the DNA repair pathways that underlie genome editing and recent improvements and strategies to yield desired genomic alterations in cells and organisms.
Mutations caused by DNA damage are a main driver of cancer. We discovered that recognition of newly synthesised histone H4 directs breast cancer type 1 susceptibility protein (BRCA1) to post-replicative chromatin. The switch from mutagenic to error-free DNA double strand break repair by homologous recombination is therefore controlled by chromatin. ...
Following DNA damage, mRNA levels decrease, reflecting a coordinated interaction of the DNA repair, transcription and RNA processing machineries. In this study, we provide evidence that transcription and polyadenylation of mRNA precursors are both affected in vivo by UV treatment. We next show that the polyadenylation factor CstF, plays a direct role in the DNA damage response. Cells with reduced levels of CstF display decreased viability following UV treatment, reduced ability to ubiquitinate RNA polymerase II (RNAP II), and defects in repair of DNA damage. Furthermore, we show that CstF, RNAP II and BARD1 are all found at sites of repaired DNA. Our results indicate that CstF plays an active role in the response to DNA damage, providing a link between transcription-coupled RNA processing and DNA repair.
Inborn defects in DNA repair mechanisms are associated with cancer, aging but also complex metabolic and endocrine disorders. Integrity of the genome is critical for normal cellular function but the DNA is continually challenged by intrinsic and extrinsic genotoxic factors. To counteract DNA damage, cells have evolved DNA repair mechanisms ensuring that the genome remains functionally intact and is faithfully transmitted to progeny. Nucleotide excision repair (NER) is a major DNA repair mechanism that cells employ to remove a wide class of bulky, DNA-distorting lesions from the genome. The importance of NER defects in man is illustrated by rare syndromes that either show increased cancer predisposition or dramatic features of accelerated aging, including depletion of fat depots. However, with the exception of cancer and aging, the links between defects in NER and the rapid onset of developmental defects in humans are not well understood.. Research carried out at the Institute of Molecular ...
Required for radiation resistance and meiotic viability and presumably acts in recombination and recombinational DNA repair pathways.
Mono- and Stereopictres of 5.0 Angstrom coordination sphere of Magnesium atom in PDB 1cw0: Crystal Structure Analysis of Very Short Patch Repair (Vsr) Endonuclease in Complex With A Duplex Dna
Efficient and correct repair of DNA damage, especially DNA double-strand breaks (DSBs), is vital for the survival of individual cells and organisms. Defects in the DNA repair may lead to cell death or genomic instability and development of cancer. The repair of DSBs in cell lines with different DSB rejoining capabilities was studied after exposure to ionising radiation. A new cell lysis protocol performed at 0ºC, which prevents the inclusion of non-true DSBs in the quantification of DSBs by pulsed-field gel electrophoresis (PFGE), was developed. Results showed that when the standard protocol at 50ºC was used, 30-40% of the initial yield of DSBs corresponds to artifactual DSBs. 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.. Non-homologous end-joining (NHEJ) is the major DSB repair pathway in mammalian cells. We show that DSBs are processed into long single-stranded DNA (ssDNA) ...
Kim, M.; Kang, H-Gyoung.; Lee, S.Yup.; Lee, H.Cheol.; Lee, E.Bae.; Choi, Y.Young.; Lee, W.Kee.; Cho, S.; Jin, G.; Jheon, H-Sung.; Son, J.Woong.; Lee, M-Hoon.; Jung, D.Kju.; Cha, S.Ick.; Kim, C.Ho.; Kang, Y.Mo.; Kam, S.; Jung, T.Hoon.; Jheon, S.; Park, J.Yong., 2010: Comprehensive analysis of DNA repair gene polymorphisms and survival in patients with early stage non-small-cell lung cancer
Grain counting by eye is a tedious and time-consuming technique but one with great potential in cell kinetics and for the study of DNA excision repair activity (unscheduled DNA synthesis or UDS). We have been investigating the levels of UDS in human skin sections exposed in situ to ultraviolet radiation using a short-term incubation in tritiated thymidine and autoradiography and the decline in UDS levels with time (repair kinetics). We have adapted an automated image analysis system automatically to assess the number of grains over epidermal cell nuclei in autoradiographs of sections of epidermis. An excellent correlation was observed between visual counting and machine measurement of the area (in pixels) occupied by silver grains. The levels of UDS declined with time as lesions are progressively repaired. The half time (+/- standard deviation) for the reduction in UDS is 7.25 +/- 0.18 h. The grain counts can be significantly increased by increasing the autoradiographic exposure, by increasing ...
Instability: Mutation and DNA repair Mutations DNA repair Instability: Mutation and DNA repair Substitution rates vary throughout the genome. Instability: Mutation and DNA
TY - JOUR. T1 - DNA repair gene variants in relation to overall cancer risk. T2 - A population-based study. AU - Alberg, Anthony J.. AU - Jorgensen, Timothy J.. AU - Ruczinski, Ingo. AU - Wheless, Lee. AU - Shugart, Yin Yao. AU - Berthier-Schaad, Yvette. AU - Kessing, Bailey. AU - Hoffman-Bolton, Judith. AU - Helzlsouer, Kathy J.. AU - Linda Kao, W. H.. AU - Francis, Lesley. AU - Alani, Rhoda M.. AU - Smith, Michael W.. AU - Strickland, Paul Timothy. PY - 2013/1. Y1 - 2013/1. N2 - The hypothesis that germ-line polymorphisms in DNA repair genes influence cancer risk has previously been tested primarily on a cancer site-specific basis. The purpose of this study was to test the hypothesis that DNA repair gene allelic variants contribute to globally elevated cancer risk by measuring associations with risk of all cancers that occurred within a population-based cohort. In the CLUE II cohort study established in 1989 in Washington County, MD, this study was comprised of all 3619 cancer cases ...
Crosslinked DNA is repaired in cells by a combination of enzymes and other factors from the nucleotide excision repair (NER) pathway, homologous recombination, and the base excision repair (BER) pathway. To repair interstrand crosslinks in eukaryotes, a 3 flap endonuclease from the NER, XPF-ERCC1, is recruited to the crosslinked DNA, where it assists in unhooking the DNA by cleaving the 3 strand at the crosslink site. The 5 strand is then cleaved, either by XPF-ERCC1 or another endonuclease, forming a double-strand break (DSB), which can then be repaired by the homologous recombination pathway.[17] DNA crosslinks generally cause loss of overlapping sequence information from the two strands of DNA. Therefore, accurate repair of the damage depends on retrieving the lost information from an undamaged homologous chromosome in the same cell. Retrieval can occur by pairing with a sister chromosome produced during a preceding round of replication. In a diploid cell retrieval may also occur by ...
Gorbunova and her team were able to make their observations by working with genetically-modified mice whose cells produce green fluorescent protein (GFP) that glows each time the breaks are repaired. By tracking how many cells glowed green in different tissues, the researchers determined the efficiency of repair.. "We showed two things with these genetically-modified mice," said Gorbunova. "Not only did the efficiency of DNA repair decline with age, but the mice began using a sloppier repair mechanism, leading to more mutations, particularly in the heart and lungs.". DNA breaks occur frequently because animal cells are under constant assault from routine activities in the environment-whether by a blast of X-rays from a visit to the doctor or simply breathing in oxygen-and, as a result, the DNA molecules often get damaged.. Using the genetically modified mice, the research team can now look at how diet, medicines, and different genetic factors also affect DNA repair in mice.. "These mice may very ...
Defects in cellular DNA repair processes have been linked to genome instability, heritable cancers, and premature aging syndromes. Yet defects in some repair processes manifest themselves primarily in neuronal tissues. This review focuses on studies defining the molecular defects associated with several human neurological disorders, particularly ataxia with oculomotor apraxia 1 (AOA1) and spinocerebellar ataxia with axonal neuropathy 1 (SCAN1). A picture is emerging to suggest that brain cells, due to their nonproliferative nature, may be particularly prone to the progressive accumulation of unrepaired DNA lesions.
17. Katagiri, T., Saito, H., Shinohara, A., Ogawa, H., Kamada, N., Nakamura Y. and Y. Miki. Multiple possible sites of BRCA2 interacting with DNA repair protein Rad51. Genes, Chromosomes and Cancer, 21, 217-222. 1998, CI=43.. 18. Gasior, S., Wang, A., Kohra, Y., Shinohara, A. and D.K. Bishop. Rad52 associates with RPA and functions with Rad55 and Rad57 to assemble meiotic recombination complexes. Genes & Dev., 12, 2208-2221, 1998, CI=183.. 19. Bishop, D.K., Ear, U., Bhattacharyya, A., Calderone, C., Beckett, M., Weichselbaum, R. and A. Shinohara. Xrcc3 is required for assembly of Rad51-complexes in vivo. J. Biol. Chem., 273, 21482-21488. 1998, CI=213.. 20. Takata, M., Sasaki, M., Sonoda, E., Morrison, C., Hashimoto, M., Utsumi, H., Yamaguchi-Iwai, Y., Shinohara, A., and S. Takeda. Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in maintenance of chromosome integrity. EMBO J., 17, 5497-5508. 1998, CI=797.. 21. Nishitani, ...
DSB repair pathways. There are three DNA DSB repair pathways: single-strand annealing (SSA), homologous recombination (HR), and nonhomologous end-joining (NHEJ) (51). In SSA, which requires homologous sequences to flank the break site, the nonhomologous DNA ends are removed, leaving overhangs that are aligned and annealed (45). After annealing, DNA synthesis and ligation occur. SSA results in deletion of the region between homologous sequences. In contrast, HR is a relatively error-free mechanism for DSB repair that relies on the homologous region on the sister chromatid as a template for DNA synthesis (Figure 6A) (1;16). HR is limited to replicating cells (including early embryonic developmental stages) and can be observed only after DNA replication in the S and G2 phases (52) . Finally, NHEJ is a rapid repair mechanism that simply ligates broken DNA ends after minimal or no processing (Figure 6B). NHEJ occurs in all phases of the cell cycle and is thought to be the primary DNA repair pathway ...
FUNCTION: Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. MSH6 provides substrate-binding and substrate-specificity to the complex. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs. Acts mainly to repair base-base and single insertion-deletion mismatches that occur during replication, but can also repair longer insertion-deletion loops (IDLs), although with decreasing efficiency as the size of the extrahelical loop increases. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis by the MutS alpha complex is crucial for MMR. Both subunits bind ATP, but with differing affinities, and their ATPase kinetics are also very different. MSH6 binds and ...
Following the irradiation of non-dividing yeast cells with ultraviolet (UV) light, most induced mutations are inherited by both daughter cells, indicating that complementary changes are introduced into both strands of duplex DNA prior to replication. Early analyses demonstrated that such "two-strand" mutations depend on functional nucleotide excision repair (NER), but the molecular mechanism of this unique type of mutagenesis has not been further explored. In the experiments reported here, an ade2 adeX colony-color system was used to examine the genetic control of UV-induced mutagenesis in non-dividing cultures of Saccharomyces cerevisiae. We confirmed a strong suppression of two-strand mutagenesis in NER-deficient backgrounds, and demonstrated that neither mismatch repair nor interstrand crosslink repair affects the production these mutations. By contrast, proteins involved in the error-prone bypass of DNA damage (Rev3, Rev1, PCNA, Rad18, Pol32 and Rad5) and in the early steps of the DNA-damage ...
Cisplatin is a crucial agent in the treatment of many solid tumors, yet many tumors have either acquired or intrinsic resistance to the drug. We have used the homozygous diploid deletion pool of Saccharomyces cerevisiae, containing 4728 strains with individual deletion of all nonessential genes, to systematically identify genes that when deleted confer sensitivity to the anticancer agents cisplatin, oxaliplatin, and mitomycin C. We found that deletions of genes involved in nucleotide excision repair, recombinational repair, postreplication repair including translesional synthesis, and DNA interstrand cross-link repair resulted in sensitivity to all three of the agents, although with some differences between the platinum drugs and mitomycin C in the spectrum of required translesional polymerases. Putative defective repair of oxidative damage (imp2Delta strain) also resulted in sensitivity to platinum and oxaliplatin, but not to mitomycin C. Surprisingly in light of their different profiles of ...
Nucleotide excision repair is a DNA repair mechanism. DNA constantly requires repair due to damage that can occur to bases from a vast variety of sources including chemicals but also ultraviolet (UV) light from the sun
BACKGROUND: Several genes encoding for DNA repair molecules implicated in maintaining genomic integrity have been proposed as cancer-susceptibility genes. Although efforts have been made to create synopses for specific fields that summarize the data from genetic association studies, such an overview is not available for genes involved in DNA repair. METHODS: We have created a regularly updated database of studies addressing associations between DNA repair gene variants (excluding highly penetrant mutations) and different types of cancer. Using 1087 datasets and publicly available data from genome-wide association platforms, meta-analyses using dominant and recessive models were performed on 241 associations between individual variants and specific cancer types that had been tested in two or more independent studies. The epidemiological strength of each association was graded with Venice criteria that assess amount of evidence, replication, and protection from bias. All statistical tests were ...
Modern light microscopical techniques were employed to follow dynamical nuclear processes during the cell cycle and during DNA-repair. Laser-UVA-microirradiation The protein Rad51 is essential for the repair of double-strand breaks (DSBs) via the conservative homologous recombination repair pathway. To test the hypothesis that Rad51 localizes to damaged sites during DSB repair, a laser-UVA-microirradiation system was established. With this system spots with sizes around 1 µm in nuclei of living cells can be irradiated with UVA-light. After sensitization of cells by incorporation of BrdU into nuclear DNA and staining with the live cell dye Hoechst 33258, the system can be used to introduce double-strand breaks and single-strand breaks in the irradiated spots. The response of Rad51 to microirradiation By use of laser-UVA microirradiation the localization of Rad51 at damaged sites containing DNA double-strand breaks could be demonstrated. The accumulation of Rad51 at microirradiated sites was ...
Nucleotide excision repair is a DNA repair mechanism. There are three excision repair pathways: nucleotide excision repair (NER ... WRNp is active in unwinding DNA, a step necessary in DNA repair and DNA replication.[10][11] Since WRNp's function depends on ... base excision repair (BER), and DNA mismatch repair (MMR). In NER, the damaged DNA strand is removed and the undamaged strand ... These genes are all involved in the NER repair pathway that repairs damaged DNA. The variant form, XP-V, is caused by mutations ...
... and double-strand breaks in DNA can be repaired.[67] The DNA checkpoint kinase ATM has a key role in integrating progression ... DNA damage and repair. Plants are continuously exposed to a range of biotic and abiotic stresses. These stresses often cause ... Roldán-Arjona, T.; Ariza, R.R. (2009). "Repair and tolerance of oxidative DNA damage in plants". Mutation Research. 681 (2-3): ... Koppen, G.; Verschaeve, L. (2001). "The alkaline single-cell gel electrophoresis/comet assay: a way to study DNA repair in ...
"DNA Repair. 71: 69-81. doi:10.1016/j.dnarep.2018.08.009. PMC 6340742. PMID 30190235.. ... DNA replication. References[edit]. *^ Thomas M, White RL, Davis RW (July 1976). "Hybridization of RNA to double-stranded DNA: ... Actively transcribed regions of DNA often form R-loops that are vulnerable to DNA damage. Introns reduce R-loop formation and ... Three-stranded nucleic acid structure, composed of a DNA:RNA hybrid and the associated non-template single-stranded DNA. ...
DNA 2007-02-13 DNA repair 2004-09-15 Endometrial cancer 2014-12-09 ...
"Meiosis as an Evolutionary Adaptation for DNA Repair". In Kruman, Inna. DNA Repair. doi:10.5772/25117 . ISBN 978-953-307-697-3. ... "Meiosis as an Evolutionary Adaptation for DNA Repair". In Kruman I. DNA repair. InTech. doi:10.5772/1751. ISBN 978-953-307-697- ... These offspring may be clones of the mother, or in some cases genetically differ from her but inherit only part of her DNA. ... in long-established self-fertilising plants may be related to the immediate benefit of efficient recombinational repair of DNA ...
"DNA Repair. 8 (9): 1004-8. doi:10.1016/j.dnarep.2009.04.006. PMC 2725225. PMID 19464237.. ...
DNA synthesis involved in DNA repair. • interstrand cross-link repair. • response to glucoside. • DNA recombinase assembly. • ... DNA repair. • response to X-ray. • response to drug. • DNA unwinding involved in DNA replication. • cellular response to ... Many cancers have epigenetic deficiencies in various DNA repair genes (see Frequencies of epimutations in DNA repair genes in ... DNA binding. • DNA-dependent ATPase activity. • recombinase activity. • chromatin binding. • DNA polymerase binding. • protein ...
... and it undergoes many structural changes as different cellular events such as DNA replication, DNA repair, and transcription ... the DNA metabolic enzymes flap endonuclease-1, thymine DNA glycosylase, and Werner syndrome DNA helicase, STAT6, Runx1 (AML1), ... If garcinol is successful at inhibiting the process of non-homologous end joining, a DNA repair mechanism that shows preference ... If histone acetyltransferases are inhibited, then damaged DNA may not be repaired, eventually leading to cell death. ...
DNA Repair (Amst.). 5 (9-10): 1234-1245. doi:10.1016/j.dnarep.2006.05.013. PMID 16793349.. ... found in DNA upstream of each constant region gene (except in the δ-chain). The DNA strand is broken by the activity of a ... RAG proteins play an important role with V(D)J recombination in cutting DNA at a particular region.[39] Without the presence of ... Lieber MR, Yu K, Raghavan SC (2006). "Roles of nonhomologous DNA end joining, V(D)J recombination, and class switch ...
"DNA repair and systemic lupus erythematosus". DNA Repair (Amst.). 56: 174-182. doi:10.1016/j.dnarep.2017.06.020. PMC 5543809. ... Evidence that mutations in DNA repair genes are implicated in SLE was reviewed by Meas et al.[53] ... Cells derived from SLE patients are unable to repair DNA damages as efficiently as control cells, and it has been suggested ... These stimuli begin a reaction that leads to destruction of other cells in the body and exposure of their DNA, histones, and ...
DNA Repair (Amst.). 9 (5): 542-50. doi:10.1016/j.dnarep.2010.02.004. PMID 20197241. Nemec AA, Wallace SS, Sweasy JB (2010). " ... DNA glycosylase NEIL1 prevents mutagenesis by 8-oxo-dG and removes formamidopyrimidines from DNA. However, cigarette smokers ... high levels of DNA amplifications, interchromosomial rearrangements, or changes in DNA methylation patterns, the latter being ... p53 prevents cell growth when DNA is damaged by activating apoptosis and p21, a kinase that blocks the formation of cyclin D / ...
Sii-Felice K, Barroca V, Etienne O, Riou L, Hoffschir F, Fouchet P, Boussin FD, Mouthon MA (2008). "Role of Fanconi DNA repair ... DNA interstrand crosslinks are highly deleterious damages that are repaired by homologous recombination involving coordination ... Loss of FANCG causes neural progenitor apoptosis during forebrain development, likely related to defective DNA repair. (Sii- ... The main cellular phenotype is hypersensitivity to DNA damage, particularly inter-strand DNA crosslinks. The FA proteins ...
This is because of self-repair mechanisms which repair the damage to DNA and other biomolecules such as proteins. These ... The DNA self repair processes in some organisms is exceptionally good; for instance, the bacterium Deinococcus radiodurans can ... John Kimball (8 April 2012). "DNA repair". Retrieved 2012-06-24. Ben Best. "Mechanisms of Aging". Retrieved 2012-06-24. Pollack ...
The PALB2-BRCA1 interaction is likely important for repairing such damages during male meiosis. Fanconi anemia BRCA2 DNA repair ... The function of homologous recombination during meiosis appears to be repair of DNA damages, particularly double-strand breaks ... DNA Repair. 10 (5): 518-25. doi:10.1016/j.dnarep.2011.02.007. PMID 21466974. Stolz A, Ertych N, Bastians H (February 2011). " ... "Homologous recombinational repair of DNA double-strand damage"). PALB2 can function synergistically with a BRCA2 chimera ( ...
Hofmann K (April 2009). "Ubiquitin-binding domains and their role in the DNA damage response". DNA Repair. 8 (4): 544-56. doi: ... Zhou W, Wang X, Rosenfeld MG (January 2009). "Histone H2A ubiquitination in transcriptional regulation and DNA damage repair". ... Monoubiquitinated PCNA recruits polymerases that can carry out DNA synthesis with damaged DNA; but this is very error-prone, ... Ubiquitination of histone H2AX is involved in DNA damage recognition of DNA double-strand breaks. Lysine 63-linked ...
DNA repair. 9 (6): 678-89. doi:10.1016/j.dnarep.2010.03.005. PMC 2896008 . PMID 20413351. Shiraishi, T; Druck, T; Mimori, K; ... introducing breaks from unreplicated regions of DNA. Late-replication may be a result of formation of non-B DNA structures like ... DNA polymerase has been shown to pause at CTG and CGG triplet repeat sequences, which can result in continual expansion via ... The CGG and AT-rich repeats characteristic of RFSs can form hairpins and other non-B DNA structures that block replication ...
Meiosis as an Evolutionary Adaptation for DNA Repair". In Inna Kruman. DNA Repair. InTech Open Publisher. doi:10.5772/25117. ... The Sgs1 helicase appears to promote the non-crossover outcome of meiotic recombinational repair of DNA, a pathway that ... In T. thermophila this process of meiotic recombination may be beneficial for repairing DNA damages caused by starvation. ... thermophila utilize a Rad51-dependent recombinational pathway to repair damaged DNA. The Rad51 recombinase of T. thermophila is ...
Lovejoy, Courtney A.; Cortez, David (2009). "Common mechanisms of PIKK regulation". DNA Repair. 8 (9): 1004-8. doi:10.1016/j. ...
The legacy of the access-repair-restore model". DNA Repair. 36: 114-21. doi:10.1016/j.dnarep.2015.09.014. PMID 26429064. ... Zhang, K; Gao, Y; Li, J; Burgess, R; Han, J; Liang, H; Zhang, Z; Liu, Y (2016). "A DNA binding winged helix domain in CAF-1 ... Hoek, M.; Stillman, B. (2003). "Chromatin assembly factor 1 is essential and couples chromatin assembly to DNA replication in ... Polo, Sophie E.; Almouzni, Geneviève (2015). "Chromatin dynamics after DNA damage: ...
This methylation damages the DNA and triggers the death of tumor cells. However, some tumor cells are able to repair this type ... Jacinto FV, Esteller M (August 2007). "MGMT hypermethylation: a prognostic foe, a predictive friend". DNA Repair. 6 (8): 1155- ... by expressing a protein O6-alkylguanine DNA alkyltransferase (AGT) encoded in humans by the O-6-methylguanine-DNA ... The therapeutic benefit of temozolomide depends on its ability to alkylate/methylate DNA, which most often occurs at the N-7 or ...
All photosensitive TTD syndromes have defects in the nucleotide excision repair (NER) pathway, which is a vital DNA repair ... Trichothiodystrophy view from the molecular basis of DNA repair transcription factor TF11H.www.oxfordjournals.org/content/18/R2 ... DNA Repair. 9 (1): 2-10. doi:10.1016/j.dnarep.2009.10.005. PMID 19931493. James, William; Berger, Timothy; Elston, Dirk (2005 ... NER is a multi-step pathway that removes a variety of different DNA damages that alter normal base pairing, including both UV- ...
Mimitou, EP; Symington, LS (2 September 2009). "DNA end resection: Many nucleases make light work". DNA repair. 8 (9): 983-995 ... The DNA repair function of SLX4 is involved in sensitivity to proton beam radiation. Model organisms have been prominent in the ... SLX4 (also known as BTBD12 and FANCP) is a protein involved in DNA repair, where it has important roles in the final steps of ... 10 July 2009). "Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair". Cell. 138 (1): ...
The protein is required for the non-homologous end joining (NHEJ) pathway of DNA repair. Patients with XLF mutations also have ... These NHEJ1 deficient cells possess a weak NHEJ1-mediated repair capacity that is apparently incapable of coping with DNA ... Revy P, de Villartay JP (2006). "[Cernunnos, a novel DNA repair factor essential for the immune system]". Médecine Sciences. 22 ... Lu H, Pannicke U, Schwarz K, Lieber MR (Apr 2007). "Length-dependent binding of human XLF to DNA and stimulation of XRCC4.DNA ...
"DNA repair decline during mouse spermiogenesis results in the accumulation of heritable DNA damage". DNA Repair. 7 (4): 572-81 ... induces DNA lesions during meiosis that may persist in an unrepaired state as germ cells progress though DNA repair-competent ... Marchetti F, Essers J, Kanaar R, Wyrobek AJ (2007). "Disruption of maternal DNA repair increases sperm-derived chromosomal ... Marchetti F, Bishop J, Gingerich J, Wyrobek AJ (2015). "Meiotic interstrand DNA damage escapes paternal repair and causes ...
Martín, C. M.; Guzmán, E. C. (2011). "DNA replication initiation as a key element in thymineless death". DNA Repair. 10 (1): 94 ... futile DNA repair, replication origin destruction, and an addiction module. Ahmad, S. I.; Kirk, S. H.; Eisenstark, A. (October ... The molecular mechanism of thymineless death remains unknown; DNA breaks were observed during thymineless death, which could ... Kuong, K. J.; Kuzminov, A. (2010). "Stalled replication fork repair and misrepair during thymineless death in Escherichia coli ...
Dysfunction of lamin A triggers a DNA damage response and cellular senescence. DNA Repair (Amst.). 2006, 5 (2): 286-9. PMID ...
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... and its biological roles in base excision DNA repair. This DNA repair pathway protects cells against endogenous DNA lesion ... the study of gap-filling DNA synthesis in DNA repair. To define the biological role of DNA polymerase beta, the group and ... DNA Repair & Nucleic Acid Enzymology Group. Mechanisms of DNA Synthesis. Samuel H. Wilson, M.D. Principal Investigator Tel 984- ... the study of gap-filling DNA synthesis in DNA repair ("/Rhythmyx/assembler/render?sys_contentid=53298&sys_revision=1&sys_ ...
... and its biological roles in base excision DNA repair. This DNA repair pathway protects cells against endogenous DNA lesion ... the study of gap-filling DNA synthesis in DNA repair. To define the biological role of DNA polymerase beta, the group and ... the study of gap-filling DNA synthesis in DNA repair. *Structural analysis to improve understanding of the fundamental ... mouse fibroblast cell lines are deficient in DNA repair and in cellular protection against DNA damaging agents, thus ...
There are two general classes of DNA repair; the direct reversal of the chemical process generating the damage and the ... Sunderland (MA): Sinauer Associates: DNA Repair.. *Eker, A.P. et al. 2009. DNA repair in mammalian cells: Direct DNA damage ... The direct reversal DNA repair mechanism. Direct reversal of DNA damage is a mechanism of repair that does not require a ... DNA double strand break repair. The repair of damage to both DNA strands is particularly important in maintaining genomic ...
It takes round-the-clock maintenance just to keep your DNA in safe working order. And its a service you really dont want to ... Back in the 1950s, no one gave much thought to DNA damage. "Historically, it was assumed for many years that DNA must be a ... That view still prevailed when Watson and Crick worked out the structure of the DNA molecule. "The idea of repair didnt occur ... a biologist at Stanford University in California who co-discovered one of the first DNA repair systems in bacteria back in 1963 ...
However, unlike replication and transcription, DNA repair systems may be required anywhere, and at any time, whenever DNA ... DNA damage repair: anytime, anywhere?. Essers J1, Vermeulen W, Houtsmuller AB. ... Regulation of the DNA damage response is tightly connected to transcription and replication. These DNA transacting processes ... Currently, quantitative live cell imaging techniques combined with methods to induce local DNA damage in a small region of the ...
Feig studies the proteins MutS and MSH2-MSH6, which recognize defective DNA and initiate DNA repair. Natural DNA repair occurs ... "DNA damage occurs frequently and if you couldnt repair your DNA, then you wont live for very long." This is because damaged ... "We believe that DNA bending facilitates the initial recognition of the mismatched base for repair," Feig said. "Normal DNA is ... In these cases, cancer is not a result of damaged DNA, but occurs because of a problem in the DNA repair mechanism itself. ...
DNA repair can, moreover, be monitored electrically. Exposure of photolyase on T,,T-damaged DNA films to near-UV/blue light ... DNA-modified gold surfaces have recently been used in the study of DNA repair proteins possessing [4Fe-4S] clusters, such as ... T,,T Repair Probed Electrochemically. Photoactivation of photolyase bound to DNA containing T,,T lesions leads to the repair of ... 6). The surface DNA has the same retention time as undamaged DNA, indicating that the T,,T damage has been repaired on the ...
A new study explores the effect of night shifts on melatonin levels and DNA repair, as indicated by a chemical byproduct ... Now, new research examines how night shifts influence the body's ability to repair its DNA. The first author of the study ... Furthermore, the authors note that a so-called NER molecular pathway is believed to play a key role in DNA damage repair - and ... Night shifts may inhibit DNA repair. Dr. Bhatti and colleagues selected 50 shift workers from the 223 included in their former ...
... the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ... This entry represents the DNA double-strand break repair and V(D)J recombination protein XRCC4, which is found in certain ... XRCC4 binds to DNA, and to DNA ligase IV (LIG4) to form the LIG4-XRCC4 complex [PMID: 11029705]. The LIG4-XRCC4 complex is ... Requirement for XRCC4 and DNA ligase IV in alignment-based gap filling for nonhomologous DNA end joining in vitro.. Cancer Res. ...
... for repairing any damage). Nevertheless, most organisms can undergo some sort of... ... Birge E.A. (1994) DNA Repair and Simple Recombination. In: Bacterial and Bacteriophage Genetics. Springer, New York, NY. * DOI ... and RecA in replicative bypass of an abasic DNA lesion by DNA polymerase III. Proceedings of the National Academy of Sciences ... Madiraju, M.V.V.S., Clark, A.J. (1992). Evidence for ATP binding and double-stranded DNA binding by Escherichia coli RecF ...
Defective DNA damage repair leads to chaos in the genome.. Defective DNA damage repair leads to frequent catastrophic genomic ... If the DNA repair is defective and Myc nevertheless stimulates the division of these damaged cells, the risk of chaos in the ... Failed DNA repair triggers chromosomal chaos in cancer cells. *Download PDF Copy ... We can use drugs to switch off additionally another important DNA repair system. This leads to so much genetic damage that the ...
... provides a forum for the comprehensive coverage of DNA repair and cellular responses to DNA damage. The journal ... DNA Repair provides a forum for the comprehensive coverage of DNA repair and cellular responses to DNA damage. The journal ... DNA Repair provides a forum for the comprehensive coverage of DNA repair and cellular responses to DNA damage. The journal ... DNA Repair sponsors GRC DNA Damage, Mutation & Cancer 2018 * 3rd DNA Replication/Repair Structures and Cancer - Fusion ...
... it results in various types of damage to the DNA within the tissues. ... NEBNext FFPE DNA Repair Mix. Protocols for FFPE DNA Repair *Protocol for use with NEBNext Ultra DNA Library Prep Kit for ... Home Applications Sample Prep for NGS & Target Enrichment FFPE DNA Repair FFPE DNA Repair. Product Listing Application Overview ... Protocol for use with NEBNext FFPE DNA Repair Mix (M6630) and NEBNext DNA Library Prep Master Mix Set for Illumina (E6040) ...
... in DNA are temporary because they are immediately corrected by a set of processes that are collectively called DNA repair. Of ... but also mechanisms for repairing the many accidental lesions that occur continually in DNA. Most such spontaneous changes ... only a few accumulate as mutations in the DNA sequence. We now know that fewer than one in 1000 accidental base changes in DNA ... the rest are eliminated with remarkable efficiency by DNA repair. ... the thousands of random changes created every day in the DNA of ...
An expert in DNA repair says the amount of damage caused to our DNA each day is astounding - an estimated 50,000 lesions per ... Nobel shows link between DNA repair, diseases An expert in DNA repair says the amount of damage caused to our DNA each day is ... Nobel shows link between DNA repair, diseases An expert in DNA repair says the amount of damage caused to our DNA each day is ... STOCKHOLM (AP) - An expert in DNA repair says the amount of damage caused to our DNA each day is astounding - an estimated ...
... and functional aspects of DNA and RNA research. ... DNA mismatch repair (MMR) is a highly conserved DNA repair ... correlation of mismatch repair and DNA recombination," DNA Repair, vol. 2, no. 4, pp. 387-405, 2003. View at Publisher · View ... and the single-stranded DNA-binding protein SSB. DNA polymerase III and DNA ligase fill the gap to complete the repair. (c) E. ... in cooperation with the single-stranded DNA-binding protein RPA. The DNA strand is resynthesized by DNA polymerase and DNA ...
Previous section The Chemistry of the Addition of Substrates of DNA Replication Next section DNA Proof-Reading and Repair ... While DNA replication does occur in the 5 to 3 direction, the reason is not because 3 to 5 replication is chemically ... DNA replication occurs in the 5 to 3 direction because 3 to 5 replication is chemically impossible. Explain your answer. ... The chemical addition of nucleotides to a growing DNA chain is dictated by the parent strand that is being copied. A nucleoside ...
In other words, it looks like Cisplatin can both damage and repair DNA. Unfortunately Cisplatin does not repair the damaged DNA ... healthy DNA to the damaged DNA in the cancer cells. We believe that they also mediate the repair of the DNA like the Cisplatin ... Likewise, whenever the body needs to repair a cellular defect, the DNA must unwind so repair enzymes can snip off the defective ... physical DNA the ORMUS elements can facilitate the repair of the DNA to this healthy template. Let s examine these concepts. ...
... directly regulates the expression of a variety of genes whose protein products are involved in DNA damage repair. ... scientists have identified at least five genes that code for DNA repair proteins, whose only job is to fix your DNA when it is ... DNA repair usually works by correcting one strand to match another template strand. It would not fix an inherited mutation ... 5 Responses to Vitamin D and DNA repair. *. PeterVermont. January 17, 2012 at 5:11 am ...
DNA »DNA repair »Max Planck Institute »Max-Planck-Institut »Proteomics »damaged DNA »daughter cells »genomic »machinery » ... Further reports about: , DNA , DNA repair , Max Planck Institute , Max-Planck-Institut , Proteomics , damaged DNA , daughter ... Proteomics identifies DNA repair toolbox. 04.05.2015. Various repair mechanisms help our cells to revert damage to their DNA. ... DNA repair requires many factors, but so far there have not been comprehensive analyses of the intricate pathways involved. ...
... model of DNA repair, in which MutS proteins are the beads and DNA is the string. In solution, the MutS protein will bind to a ... A new and detailed look at the role of MutS in DNAs mismatch repair (MMR) system has been provided by a team of researchers ... "This is the first time we used this technique to look at a protein-mediated process like DNA repair in solution with multiple ... "The view of DNA as a passive element is at least in part due to a paucity of robust tools for examining dynamic DNA ...
One or more of these pathways are mutagenic, i.e., induce mutations during the process of repair of lesions in DNA.... ... DNA repair pathways have been identified in the yeast Saccharomyces cerevisiae. ... Resnick, M. A., The repair of double-strand breaks in chromosomal DNA of yeast, In: Molecular Mechanisms for Repair of DNA, ... Johnston, L. H., The DNA repair capability of cdc9, the Saccharomyces cerevisiae mutant defective in DNA ligase, Mol. Gen. ...
... the cells natural DNA repair process can add or remove bits of DNA at the break site in a seemingly random and unpredictable ... Scientists interested in repairing pathogenic mutations can query the site to see where they might be able to cut DNA and get ... Predicting how cells repair broken DNA Written By. Leah Eisenstadt, Broad Institute ... To restore gene function without templated repair requires knowing how the cell will fix CRISPR-induced DNA breaks-knowledge ...
A complex DNA repair machinery has evolved to protect genomic integrity in the face of a myriad of DNA damage sources. When DNA ... DNA repair defects and implications for immunotherapy. Katherine M. Bever and Dung T. Le Sidney Kimmel Comprehensive Cancer ... Indeed, many heritable cancer predisposition syndromes are attributable to germline defects in DNA repair pathways. On the ... Most recently this has been demonstrated in the case of mismatch repair-deficient cancers, in which the immune checkpoint ...
  • Feig studies the proteins MutS and MSH2-MSH6, which recognize defective DNA and initiate DNA repair. (redorbit.com)
  • Natural DNA repair occurs when proteins like MutS (the primary protein responsible for recognizing a variety of DNA mismatches) scan the DNA, identify a defect, and recruit other enzymes to carry out the actual repair. (redorbit.com)
  • These results demonstrate the exquisite sensitivity of DNA electrochemistry to perturbations in base pair stacking and the applicability of this chemistry to probe reactions of proteins with DNA. (pnas.org)
  • DNA-modified gold surfaces have recently been used in the study of DNA repair proteins possessing [4Fe-4S] clusters, such as MutY and EndoIII ( 12 , 13 ). (pnas.org)
  • Our investigations indicate that DNA binding is requisite for the redox activity of these proteins and that CT from the electrode surface to the [4Fe-4S] cluster occurs in a DNA-mediated fashion. (pnas.org)
  • Activity of the purified mutagenesis proteins UmuC, UmuD', and RecA in replicative bypass of an abasic DNA lesion by DNA polymerase III. (springer.com)
  • Postreplicative MMR is performed by the long-patch MMR mechanism in which multiple proteins are involved and a relatively long tract of the oligonucleotide is excised during the repair reaction [ 9 , 10 ]. (hindawi.com)
  • Unbelievably, scientists have identified at least five genes that code for DNA repair proteins, whose only job is to fix your DNA when it is broken. (vitamindcouncil.org)
  • Their results shed light on the repair mechanism and identified new proteins and drug targets that could be important in maintaining genomic stability and preventing cancer. (innovations-report.com)
  • To monitor such changes, they isolated DNA at several time points during the replication and repair process, and quantified the bound proteins using mass spectrometry based proteomics. (innovations-report.com)
  • These include many known DNA repair factors, as well as new proteins of previously unknown function. (innovations-report.com)
  • Together with the team of Professor Mailand at the Center for Protein Research in Copenhagen, Denmark, they are now analyzing whether and how these proteins promote the repair process. (innovations-report.com)
  • It is a common belief that DNA is a passive component in protein interactions that involve DNA metabolism, but many proteins actually make use of DNA structural features, such as rigidity and conformation for important biological processes," Tainer says. (redorbit.com)
  • The SAXS study at the SIBYLS beamline validated what has been dubbed the "beads-on-a-string" model of DNA repair, in which MutS proteins are the beads and DNA is the string. (redorbit.com)
  • Unlike proteins and RNA , DNA usually lacks tertiary structure and therefore damage or disturbance does not occur at that level. (bionity.com)
  • DNA is, however, supercoiled and wound around "packaging" proteins called histones (in eukaryotes), and both superstructures are vulnerable to the effects of DNA damage. (bionity.com)
  • Damaged DNA, specifically collapsed replication forks and persistent double-stranded breaks, is transferred to the nuclear pores, where nuclear pore components and other proteins facilitate recombinational repair. (sciencemag.org)
  • The damaged regions of DNA are recruited to the peripheral regions of the nucleus by a complex of nuclear-pore and ubiquitin-modifying proteins, where it is repaired. (sciencemag.org)
  • By using proteins with peptide tags or antibodies to the repair factors in electrophoretic mobility shift assays, it was found that XPA, replication protein A, transcription factor IIH, XPG, and XPF⋅excision repair cross-complementing 1 but not XPC⋅HHR23B were present in the penultimate and ultimate dual incision complexes. (pnas.org)
  • However, there are no reports on the interactions of these proteins with DNA fragments containing a single lesion. (pnas.org)
  • In this study, we have identified the minimum set of repair factors required for formation of a high affinity and specificity DNA-protein complex and physically have separated this complex from the free DNA and proteins in the reaction mixture by electrophoresis on nondenaturing polyacrylamide gels. (pnas.org)
  • That's DNA methylation, which (among other things) is used as a sort of time stamp: unmethylated stretches of DNA are freshly laid down, and there are whole suites of proteins that go over them and can bind to errors. (sciencemag.org)
  • A veritable hive of proteins swarms around DNA, looking for mistakes and patching them up. (asbmb.org)
  • In cell nucleus, DNA is wound around cores made of histone proteins. (businesswire.com)
  • One of the histone proteins, H2AX, plays important role in recognition of DNA damage. (businesswire.com)
  • New research performed on lab-grown human skin suggests that short but powerful bursts of THz radiation may both cause DNA damage and increase the production of proteins that help the body fight cancer. (businesswire.com)
  • At the same time, they observed THz-pulse induced increases in the levels of multiple tumor suppressor and cell-cycle regulatory proteins that facilitate DNA repair. (businesswire.com)
  • DNA, which carries instructions for building proteins necessary for life, is occasionally mistranslated. (earthtimes.org)
  • Repair proteins help correct such mistakes. (earthtimes.org)
  • But among certain leukemia patients, the repair proteins themselves are defective, due to a genetic defect. (earthtimes.org)
  • Or, it can issue signals from the checkpoint proteins to put the cells into "cell cycle arrest," causing them to remain quiescent while the broken DNA is fixed before they resume normal activity. (scienceblog.com)
  • Repair-blocking drugs are designed to squelch the checkpoint proteins' signals, preventing the chemotherapy-damaged cancer cells from initiating the rest phase and undergoing repairs. (scienceblog.com)
  • At the same time, a flock of repair proteins are recruited to the site of the DNA damage. (scienceblog.com)
  • To find out if this overlap might pose a problem for cdk-inhibitor therapy, the researchers disabled just one of the proteins - cdk1 - in cultured lung cancer cells and treated the cells with cisplatin, a DNA-damaging agent. (scienceblog.com)
  • This realm of research is called epigenetics, and at the heart of it is chromatin - the nucleic acids and proteins that package DNA to fit inside cells. (newswise.com)
  • However, recent work now indicates that special DNA binding proteins known as histones are the first line of defense. (extremetech.com)
  • The lowest order structure of our chromosomes, the so-called nucleosome, is basically a length of DNA wound on an octet core made from two copies of each of the four core histone proteins (H2A, H2B, H3 and H4). (extremetech.com)
  • Antibodies are a common tool in DNA repair, with hundreds of subgroups that mark specific proteins. (novusbio.com)
  • We, at Novus Biologicals, have a vast catalog of antibodies, allowing highly specific assays of a full range of DNA-related proteins. (novusbio.com)
  • It reacts with the BRCA1 and BRCA2 proteins, and this interaction is thought to be important to DNA damage cell response. (novusbio.com)
  • RNF168 binds to polyubiquitylated proteins and accumulates at the damaged DNA as part of the repair process. (nanowerk.com)
  • Because the binding of RNF168 to lysine 63 chains is imperative for the recruitment of other DNA repair proteins, the scientists investigated the molecular interactions that assure this binding. (nanowerk.com)
  • In cells, proteins tightly package the long thread of DNA into pearl necklace-like complexes known as chromatin. (phys.org)
  • In long patch‐base excision repair (LP‐BER), DNA synthesis is carried out by a complex of several proteins, including DNA polymerases δ and ɛ (Pol δ/ɛ), replication factor C (RFC) and proliferating cellular nuclear antigen (PCNA). (els.net)
  • Seluanov and his colleagues found that the decline in a cell's ability to repair DNA during aging coincided with a global reduction in the levels of proteins involved in the repair process. (rochester.edu)
  • Seluanov's group tried to reverse the age-related decline in DNA repair efficiency by restoring the proteins to their original levels and found only one protein, SIRT6, did the trick. (rochester.edu)
  • NER employs a set of specialized proteins that first scan DNA to detect a damaged region. (jove.com)
  • In eukaryotes - the group of organisms that include humans - a key to survival is the ability of certain proteins to quickly and accurately repair genetic errors that occur when DNA is replicated to make new cells. (ucsd.edu)
  • One of the major questions in MMR is how MMR proteins figure out which base in a DNA mispair is the wrong one," said Ludwig Institute assistant investigator Christopher D. Putnam, PhD, an adjunct assistant professor of medicine at UC San Diego. (ucsd.edu)
  • The actual signal was not identified, but Putnam said it might be tell-tale nicks in single-stranded DNA or certain proteins associated with replication. (ucsd.edu)
  • By looking to see how ATM and ATR reacted to damage in cells, Elledge's group found that a small molecular army -- more than 700 different proteins -- is called into physiological action when the cell's DNA is in need of repair. (science20.com)
  • Specifically, the group looked to see which proteins in the cell were chemically altered by the enzymes ATM and ATR, finding 900 sites on 700 proteins that changed in response to DNA damage. (science20.com)
  • The revelation that so many proteins are involved in repairing faulty DNA opens a molecular frontier that promises insight into a spectrum of diseases. (science20.com)
  • For example, in a companion paper, also published this week in Science, Elledge's group used the new DNA repair database to identify two proteins critical to recruiting the BRCA1 gene to sites of DNA damage. (science20.com)
  • The proteins, known as Abraxas and RAP80, bind to the BRCA1 protein and form a complex that governs three essential modes of DNA damage control: damage resistance, genetic checkpoints that constrain cell proliferation, and DNA repair. (science20.com)
  • Second, using in vivo kinetic data for the recruitment of three different proteins at local damaged nuclei, the model parameters are determined and the dynamic behavior of the repair process is scrutinized in detail. (hu-berlin.de)
  • Fanconi anemia proteins have been implicated in the repair of interstrand DNA crosslinks that block DNA replication and transcription. (nih.gov)
  • The established DNA interacting components (FANCM, FANCI, FANCD2, and FANCJ) account only for approximately 5% of all FA patients, an observation that raises doubt concerning the roles of FA proteins in DNA repair. (nih.gov)
  • In recent years, rapid progress in the area of FA research has provided great insights into the critical roles of FA proteins in DNA repair. (nih.gov)
  • However, many FA proteins do not have identifiable domains to indicate how they contribute to biological processes, particularly DNA repair. (nih.gov)
  • Researchers used fluorescently tagged antibodies to track 53BP1 (red) and another key associated protein, RIF1 (green), to see if the proteins were recruited to areas of DNA damage inside the cell nucleus (blue). (mdc-berlin.de)
  • Initial studies found that ataxin-3 interacts with two proteins, HHR23A and HHR23B, that are both homologs of the DNA repair protein Rad23 [ 2 ]. (plos.org)
  • These cell lines are devoid of all DNA polymerase β mRNA and protein, and cell extracts lack full base excision repair capacity, thus establishing a role of this particular DNA polymerase in base excision repair. (nih.gov)
  • In a paper published in the Journal of Physical Chemistry B (April 26, 2013), Feig and his research team showed that the identification and initiation of repair depended on how the MutS protein bound with the base mismatches. (redorbit.com)
  • The long-term idea is to develop strategies for compensating for this protein, basically substituting some other mechanism for recognizing defective DNA and enabling repair. (redorbit.com)
  • Cyclic and square-wave voltammograms of photolyase deposited on these electrodes show a redox signal at 40 mV versus normal hydrogen electrode, consistent with electron transfer to and from the flavin in the DNA-bound protein. (pnas.org)
  • Protein-DNA interactions can also be investigated by using these surfaces. (pnas.org)
  • Perturbations of the DNA base pair stack caused by protein binding through base flipping or kinking are clearly detected by using this methodology ( 10 ). (pnas.org)
  • Indeed, this technique can provide a sensitive probe of protein-DNA binding and reaction. (pnas.org)
  • Here, we employ DNA-modified electrodes to probe the repair protein Escherichia coli photolyase. (pnas.org)
  • This entry represents the DNA double-strand break repair and V(D)J recombination protein XRCC4, which is found in certain Metazoans, fungi and plants. (ebi.ac.uk)
  • Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends. (ebi.ac.uk)
  • Arabidopsis DNA ligase IV is induced by gamma-irradiation and interacts with an Arabidopsis homologue of the double strand break repair protein XRCC4. (ebi.ac.uk)
  • Evidence for ATP binding and double-stranded DNA binding by Escherichia coli RecF protein. (springer.com)
  • The resulting DNA segment is excised by the EXO1 exonuclease, in cooperation with the single-stranded DNA-binding protein RPA. (hindawi.com)
  • After the incision of discontinuous strand by MutL, the error-containing DNA strand is removed by the cooperative functions of DNA helicases, such as UvrD, the exonucleases RecJ and ExoI, and the single-stranded DNA-binding protein SSB. (hindawi.com)
  • DNA helicase, a single-stranded DNA-binding protein, and several exonucleases are involved in the excision reaction. (hindawi.com)
  • Using novel and highly sensitive proteomic technologies, scientists of the Max Planck Institute (MPI) of Biochemistry now report in the journal Science the first global analysis of the protein recruitment dynamics underlying a critical DNA repair pathway. (innovations-report.com)
  • To answer this question, scientists in the team of Matthias Mann at the MPI of Biochemistry in Martinsried near Munich, with colleagues in Copenhagen and at Harvard, have analyzed how the protein composition of the DNA replication machinery changes upon encountering damaged DNA. (innovations-report.com)
  • In solution, the MutS protein will bind to a mismatched DNA site by bending the DNA. (redorbit.com)
  • This is the first time we used this technique to look at a protein-mediated process like DNA repair in solution with multiple partners," Hura says. (redorbit.com)
  • When CtIP becomes activated, say the scientists, it causes the protein made by the BRCA1 gene to bind to the damaged DNA. (cancerresearchuk.org)
  • Ed Yong, Cancer Research UK's health information manager, revealed: "Our cells have two major ways of repairing broken DNA and this study shows that the CtIP protein is a switch that flicks between them. (cancerresearchuk.org)
  • In doing so, the protein helps our cells to mend damaged DNA and fix the sorts of faults that could eventually lead to cancer. (cancerresearchuk.org)
  • The study describes that after the strands of DNA are injured, tiny filaments of a protein called actin form, producing a road to the edge of the nucleus. (icr.org)
  • Individual repair factors or any combination of up to four repair factors failed to form DNA-protein complexes of high specificity and stability. (pnas.org)
  • The XPF⋅ERCC1 heterodimer changes the electrophoretic mobility of the DNA-protein complex formed with the other five repair factors, but it does not confer additional specificity. (pnas.org)
  • Recently, the enzyme system has been reconstituted from highly purified subunits consisting of XPA, replication protein A (RPA), transcription factor IIH (TFIIH), XPC⋅HHR23B, XPG, and XPF⋅ERCC1 repair factors ( 3 - 5 ). (pnas.org)
  • By using randomly damaged DNA as substrate and a variety of methods including filter binding and gel retardation assays for detecting DNA-protein complexes, it has been shown that RPA ( 9 , 10 ), XPA ( 11 , 12 ), the combination of XPA and RPA ( 13 , 14 ), and XPC ( 15 ) bind with moderately higher affinity to damaged DNA compared with undamaged DNA. (pnas.org)
  • Our data show that XPA, RPA, TFIIH, XPC⋅HHR23B, and XPG are required for high specificity DNA-protein complex formation and that XPC⋅HHR23B is a molecular matchmaker that is not present in the ultimate dual incision complex that covers an ≈30-bp region of DNA around the lesion. (pnas.org)
  • The investigation focused on a protein called MSH2, which is involved in the repair of defective DNA. (earthtimes.org)
  • About 3,000 young patients are diagnosed with ALL each year in the U.S. The present work was informed by the observation that ten years after diagnosis children with low levels of the MSH2 protein were less likely to have survived, and more likely to have suffered a relapse of their leukemia, than children with normal levels of the repair protein. (earthtimes.org)
  • But how did the loss of just the one checkpoint protein disrupt the repair process? (scienceblog.com)
  • The investigators showed that a key player in DNA repair - the BRCA1 protein best known in its mutated form as an inherited breast cancer risk factor - couldn't fulfill its mission in lung cancer cells lacking cdk1. (scienceblog.com)
  • Newswise - CHAPEL HILL, N.C. - Twelve years ago, UNC School of Medicine researcher Brian Strahl, PhD, found that a protein called Set2 plays a role in how yeast genes are expressed - specifically how DNA gets transcribed into messenger RNA. (newswise.com)
  • For instance, protein and DNA modifications involved in gene expression in kidneys must at some point be turned off. (newswise.com)
  • Some with personal experience may even recognize it as the BRC or 'Breast Cancer' terminal domain of the breast cancer DNA-repair protein of the same name, which incidentally may have some similar functionality to our H2AX. (extremetech.com)
  • Mammalian CtIP protein has major roles in DNA double-strand break (DSB) repair. (nature.com)
  • The RAD51 protein plays a major role in the repair of double strand DNA breakages. (novusbio.com)
  • http://www.sciencemag.org/cgi/content/abstract/291/5507/1284 An online Table with links to Gene Cards and NCBI gives ready access to a huge amount of information on 127 DNA repair genes and their protein products. (bio.net)
  • Mutant Htt interacts with Ku70, impairs DNA-dependent protein kinase function in nonhomologous end joining, and consequently increases DSB accumulation. (sigmaaldrich.com)
  • The two strands of DNA (grey) are split at the top of the protein and enter tunnels directing the 3' tail to the RecC Chi-recognition site and nuclease, and the 5' tail to RecD. (esrf.eu)
  • The laboratory is particularly interested in the description of the protein-protein interaction networks controlling genome stability : DNA damage signaling and repair, telomere architecture, nuclear envelope assembly and structure. (cea.fr)
  • In a series of experiments in mice with cancer and in cancer cells, they have shown that they can block the process by which leukemia stem cells repair themselves by targeting a particular protein, RAD52, which the cells depend on to fix genetic mistakes. (innovations-report.de)
  • In CML cells, the BCR-ABL1 protein shuts down the main DNA repair system and leukemia cells have to rely on a backup pathway for repair. (innovations-report.de)
  • Previous experiments in mice bone marrow cells lacking RAD52, a key protein in the backup system, showed that its absence abrogated the development of CML, proving that CML DNA repair depended on RAD52. (innovations-report.de)
  • The researchers took advantage of the fact that when the RAD52 protein is mutated in some way, it can no longer bind to DNA, which is crucial to fixing broken DNA. (innovations-report.de)
  • The team then used an "aptamer," a peptide that mimicked the area where the RAD52 protein binds to DNA, to see the effects of blocking RAD52 from binding to DNA. (innovations-report.de)
  • 1996) Cloning of a yeast 8‐oxoguanine DNA glycosylase reveals the existence of a base‐excision DNArepair protein superfamily. (els.net)
  • 2000) The lyase activity of the DNA repair protein β‐polymerase protects from DNAdamage‐induced cytotoxicity. (els.net)
  • In short patch‐base excision repair (SP‐BER), DNA polymerase β (Pol β) inserts the appropriate deoxynucleotide and cleaves the deoxyribose phosphate (dRP) group before DNA ligase III (Lig III) and X‐ray cross‐complimenting protein 1 (XRCC1) resolve the structure. (els.net)
  • Fishel M and Kelley M (2007) The DNA base excision repair protein Ape1/Ref‐1 as a therapeutic and chemopreventive target. (els.net)
  • Drugs which target this key DNA repairing enzyme in the right way, could prove vital for treating people suffering from diseases caused by the over-activation of this protein - it is now crucial we determine what diseases these are. (belfasttelegraph.co.uk)
  • That work showed that overexpressing the SIRT6 protein extended the lifespans of mice,' said Gorbunova, 'Our research looked at DNA repair and found a reason for the increased longevity, and that is SIRT6's role in promoting more efficient DNA repair. (rochester.edu)
  • Another crucial component of the DNA repair process is DNA-PK, a protein kinase that governs DNA damage response, helping to assure genetic stability. (mdanderson.org)
  • Now we have a better idea of how the BRCA1 protein is being targeted to DNA damage sites," Elledge said, and this seems to run a pretty big part of the BRCA1 program. (science20.com)
  • To understand the mechanisms underlying the protein assembly during NER and the performance of repair, a mathematical model, delineating hallmarks and general characteristics of NER, has been developed. (hu-berlin.de)
  • In addition, we are exploring the impact of the ss DNA binding protein RPA and the Cockayne syndrome B protein (CSB) on regulating Ape1 activity on ss and bubble-containing AP substrates. (aacrjournals.org)
  • An important protein that helps our bodies fight infection has long been thought to work by protecting broken DNA ends. (mdc-berlin.de)
  • The fields of immunology and DNA repair need to rethink how a key protein supports the body's immune system, according to new research published in the journal Cell Reports. (mdc-berlin.de)
  • For many years, scientists thought the protein primarily protects the ends of broken DNA strands from further damage during the normal process of producing antibodies. (mdc-berlin.de)
  • A schematic representation of the 53BP1 protein, which is known to play an important role during DNA damage response and immunity. (mdc-berlin.de)
  • Protein 53BP1 does indeed protect broken DNA strands from being damaged further before rejoining is complete. (mdc-berlin.de)
  • Chromatin is an intricate macromolecular structure that is basically found in cells, which consist of DNA, protein, and RNA. (intechopen.com)
  • The protein component of chromatin is the histones, which are primarily responsible for the compaction of DNA [ 2 ]. (intechopen.com)
  • A small protein previously associated with cell dysfunction and death in fact serves a critical function in repairing breaks in DNA, according to new research led by scientists at Oregon Health & Science University. (medicalxpress.com)
  • The reason why is not fully understood, because their cells should be able to repair DNA using the lower - but still adequate - levels of BRCA2 protein made from the remaining, intact copy of the gene. (cam.ac.uk)
  • In people who inherit one faulty copy of the BRCA2 gene, this effect pushes down BRCA2 protein levels below the amount required for adequate DNA repair, breaking down the normal mechanisms that prevent mutations, which could promote cancer formation. (cam.ac.uk)
  • A novel protein, MAPO1, that functions in apoptosis triggered by O6-methylguanine mispair in DNA. (scienceblog.com)
  • The single-strand gap created by the exonuclease can then be repaired by DNA Polymerase III (assisted by single-strand-binding protein), which uses the other strand as a template, and finally sealed by DNA ligase. (wikipedia.org)
  • Changes to the structure of DNA can cause mutations and genomic instability, leading to cancer. (news-medical.net)
  • Of the thousands of random changes created every day in the DNA of a human cell by heat, metabolic accidents, radiation of various sorts, and exposure to substances in the environment, only a few accumulate as mutations in the DNA sequence. (nih.gov)
  • Although DNA is a highly stable material, as required for the storage of genetic information, it is a complex organic molecule that is susceptible, even under normal cellular conditions, to spontaneous changes that would lead to mutations if left unrepaired ( Figure 5-46 ). (nih.gov)
  • The mutations would then be propagated throughout subsequent cell generations as the DNA is replicated. (nih.gov)
  • Mutations and epigenetic silencing in MMR genes have been implicated in up to 90% of human hereditary nonpolyposis colon cancers [ 3 - 8 ], indicating the significance of this repair system. (hindawi.com)
  • The work suggests that the cell's genetic auto-correction could one day be combined with CRISPR-based therapies that correct gene mutations by simply cutting DNA precisely and allowing the cell to naturally heal the damage. (mit.edu)
  • Using machine learning, we've shown we can often correct those mutations predictably, by simply letting the cell repair itself. (mit.edu)
  • Many disease-associated mutations involve extra or missing DNA, known as insertions and deletions. (mit.edu)
  • Most are accurately repaired, so the cell is unaffected, but some result in permanent errors (mutations or chromosome rearrangements) that lead to diseases, including cancer. (brandeis.edu)
  • Cells must repair DNA damage to prevent mutations from propagating and accumulating, and to maintain genome integrity and stability. (qiagen.com)
  • Even without donor DNA, CRISPR-Cas9 has the potential to correct disease-associated mutations in humans. (genengnews.com)
  • Template-free Cas9 editing, the article maintains, is predictable and capable of precise repair to a predicted genotype, enabling correction of disease-associated mutations in humans. (genengnews.com)
  • Daughter cells that inherit these wrong bases carry mutations from which the original DNA sequence is unrecoverable (except in the rare case of a back mutation , for example, through gene conversion). (bionity.com)
  • A byproduct of alcohol consumption causes mutations in the DNA of mouse blood stem cells, and some of the breaks are not repaired. (the-scientist.com)
  • Researchers develop a CRISPR-based technique that efficiently corrects point mutations without cleaving DNA. (the-scientist.com)
  • These non-Watson-Crick base pairs jump the rails of the entire DNA information coding system, and if allowed to accumulate, would lead to all sorts of mutations and messed-up transcription. (sciencemag.org)
  • One consequence could be that if you have broken DNA, then loss of this enzyme could lead to downstream mutations from inefficient repair. (newswise.com)
  • Mutations in many of the genes that regulate DNA interstrand cross-link repair cause Fanconi anemia , a rare disorder that can lead to infertility , bone marrow failure, and predisposition to cancer . (medicalnewstoday.com)
  • The FAN1 knockout mice that Smogorzewska's lab has generated allow them to investigate the role of FAN1 in DNA repair, and to figure out how mutations in the gene may lead to kidney disease. (medicalnewstoday.com)
  • Cells are regularly exposed to mutagens-factors in the environment which can damage DNA and generate mutations. (jove.com)
  • Broken DNA is usually very dangerous, opening the door to mutations that are more likely to lead to cancer or cell death. (mdc-berlin.de)
  • The aggressive oxygen compounds destroy genetic material , resulting in what are referred to as harmful 8-oxo-guanine base mutations in the DNA. (medicalxpress.com)
  • The authors also found mutations in several genes involved in DNA repair. (scienceblog.com)
  • The journal publishes original observations on genetic, cellular, biochemical, structural and molecular aspects of DNA repair, mutagenesis, cell cycle regulation, apoptosis and other biological responses in cells exposed to genomic insult, as well as their relationship to human disease . (elsevier.com)
  • During each cell division, more than 3.3 billion base pairs of genomic DNA have to be duplicated and segregated accurately to daughter cells. (innovations-report.com)
  • A complex DNA repair machinery has evolved to protect genomic integrity in the face of a myriad of DNA damage sources. (jci.org)
  • When DNA repair fails, this damage can lead to carcinogenesis and tumor genomic instability. (jci.org)
  • CRISPR-Cas9 has the reputation for being "snip happy," for cutting and cutting a genomic site until one of the cell's DNA repair systems finally skips a beat, leaving the site imperfectly repaired-scarred, really. (genengnews.com)
  • C in genomic DNA without DNA cleavage. (nature.com)
  • The present invention relates to the chemically modified genomic sequences of genes associated with DNA repair, to oligonucleotides and/or PNA-oligomers for detecting the cytosine methylation state of genes associated with DNA repair which are directed against the sequence, as well as to a method for. (google.com.au)
  • In this study, we report that mutant huntingtin (Htt) expression in neurons causes double-strand breaks (DSBs) of genomic DNA, and Htt further promotes DSBs by impairing DNA repair. (sigmaaldrich.com)
  • Futile cycles of TCR at naturally occurring non-canonical DNA structures might contribute to genomic instability and genetic disease. (nih.gov)
  • The central hypothesis is that IGF-1 during a critical development window activates an epigenetic switch within cells resulting in permanent modifications in the DNA repair machinery that regulate genomic stability throughout the lifespan. (ouhsc.edu)
  • Our hypothesis, based on our preliminary studies, is that shifts in the timing and/or decreases in the magnitude of the peripubertal IGF-1 surge increase genomic stability by increasing cellular DNA repair capacity. (ouhsc.edu)
  • PNKP is an enzyme with key roles in DNA damage repair, particularly maintaining genomic stability of neural cells, and in providing resistance of cancer cells to genotoxic therapeutic agents. (plos.org)
  • As reported in the journal Nature Communications , Aurélie Ernst and team identified the failure of certain genetic repair systems as one of the causes. (news-medical.net)
  • Drugs called PARP inhibitors are already clinically approved agents that block a key DNA repair system and Ernst says that if the genetic material of a tumor exhibits chromothripsis, it may be possible to treat them with PARP inhibitors in the future, although this would require confirmation in preclinical and clinical tests. (news-medical.net)
  • When DNA's double helix is broken after damage from, say, exposure to X-rays, molecular machines perform a kind of genetic "auto-correction" to put the genome back together - but those repairs are often imperfect. (mit.edu)
  • To do this, they cut the double helix with an enzyme and insert missing DNA, or remove extra DNA, using a template of genetic material that serves as a blueprint. (mit.edu)
  • For nearly three decades, Abraham and Etta Goodman Professor of Biology James Haber has studied DNA repair, the processes whereby insults to our genetic code are corrected. (brandeis.edu)
  • Similarly, when DNA is damaged, a molecular general contractor oversees a network of genetic subcontractors to ensure that the diverse cellular tasks needed to protect and repair the genome are carried out correctly and on time. (eurekalert.org)
  • Scientists have known for some time that a master gene named SOG1 acts like a general contractor for repair, coordinating with various genetic subcontractors of the plant cell to mount an effective DNA damage response. (eurekalert.org)
  • The research, which appeared in the journal Proceedings of the National Academy of Sciences during the week of October 10, 2018, reveals the genetic framework controlling a complex biological process that has broad implications for understanding how plants in particular, and organisms in general, cope with DNA damage to ensure long-term health and fitness. (eurekalert.org)
  • Telomeres help preserve DNA stability in cells by containing genetic miscues. (cincinnatichildrens.org)
  • It sends signals to activate other biochemical targets (H2AX, SMC1, NBS1 and p53) that help direct DNA repair and preserve genetic stability. (cincinnatichildrens.org)
  • During and immediately after DNA replication, cells have an option of repairing mistakes using the just-duplicated sister chromatid to avoid permanent changes to the genetic material. (asbmb.org)
  • Scientists at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have now found a cause for the frequent catastrophic events in the genetic material of cancer cells that have only been known for a few years: If an important DNA repair system of the cells has failed, this promotes fragmentation and defective assembly of the genetic material. (eurekalert.org)
  • Aurelie Ernst and her team at the German Cancer Research Center have now been able to show that the failure of certain genetic repair systems is one of the causes of chromosomal chaos. (eurekalert.org)
  • Genetic problems can also arise from the replication of DNA during cell division, which happens in your body several million times a day. (mentalfloss.com)
  • Without DNA repair, the Nobel Prize committee said, our genetic material would "disintegrate into complete chemical chaos. (mentalfloss.com)
  • The findings being reported in the Aug. 14 issue of Molecular Cell help explain the promising results being seen in clinical trials of compounds that force cancer cells with genetic damage to self-destruct instead of "resting" while their DNA undergoes repairs. (scienceblog.com)
  • Through a series of biochemical and genetic experiments, Deepak Jha, a graduate student in Strahl's lab, was able to see what happens when cells experience a break in the double-strand of DNA. (newswise.com)
  • These leukemia stem cells are full of genetic errors, loaded with potentially lethal breaks in DNA, and are in a state of constant self-repair. (innovations-report.de)
  • Published monthly since January 2002 by Elsevier , with Errol Friedberg as editor in chief , the journal publishes original research papers, short reviews, and book reviews concerning DNA repair , cell cycle regulation, cell death , and other biological responses to genetic damage. (wn.com)
  • It is linked to single-strand breaks in DNA, one of the most common types of genetic damage. (belfasttelegraph.co.uk)
  • DNA double-strand breaks (DSBs) are the worst possible form of genetic malfunction that can cause cancer and resistance to therapy. (mdanderson.org)
  • Cells have the remarkable ability to keep track of their genetic contents and -- when things go wrong - to step in and repair the damage before cancer or another life-threatening condition develops. (science20.com)
  • To see whether this function is essential for CSR, the team used genetic and biochemical tools to prevent 53BP1 from protecting the DNA ends, without affecting its other known functions. (mdc-berlin.de)
  • Testing for genetic weaknesses in repairing DNA could pick out men who may benefit from a new type of targeted nuclear medicine, a new study reports. (medicalxpress.com)
  • Any mutational event that disrupts the superhelical structure of DNA carries with it the potential to compromise the genetic stability of a cell. (wikipedia.org)
  • The DNA Repair & Nucleic Acid Enzymology Group has made a number of contributions over the years to the understanding of mechanisms of DNA synthesis and, in particular, synthesis by the repair enzyme DNA polymerase β (Pol β). (nih.gov)
  • In 1996, the group demonstrated that Pol β "knock-out" mouse fibroblast cell lines are deficient in DNA repair and in cellular protection against DNA damaging agents, thus establishing a cellular role for this enzyme. (nih.gov)
  • The group developed a strong recombinant expression system for the enzyme and then went on to obtain the first crystal structure of a DNA polymerase ternary complex: Pol β complexed with its substrates, DNA and correct incoming dNTP-Mg 2+ . (nih.gov)
  • report that a nuclear function of Bcl2 appears to be inhibition of the DNA repair enzyme APE1, which mediates the repair of apurinic/apyrimidinic (also known as abasic) sites that occur thousands of times each day in a cell due to various environmental stresses. (sciencemag.org)
  • Sheila S. David , Peter A. Beal , and colleagues investigated the DNA repair enzyme NEIL1, which initiates repair of oxidized DNA bases. (acs.org)
  • Because production of the RNA deamination enzyme is induced by an inflammatory response, the researchers propose that editing of the mRNA of NEIL1 may be a way that cells provide themselves with a broader range of DNA repair in response to the oxidative stress of inflammation. (acs.org)
  • ii ) Do all of the repair factors assemble together to form a complex capable of performing dual incisions or do some of the factors function as molecular matchmakers ( 8 ), that is, help in the assembly of the enzyme but are absent in the ultimate dual incision complex? (pnas.org)
  • A whole cascade of enzyme recognize the damaged bases, yank the DNA in that region so as to flip the altered base from the inside of the helix to the outside, cleave it off, cut the DNA nearby, and patch in a replacement. (sciencemag.org)
  • The RecBCD enzyme binds at the broken DNA end and rapidly unwinds the duplex in an ATP-dependent manner. (esrf.eu)
  • This unwinding and digestion continues until the Chi sequence is encountered, at which point the enzyme pauses, and the nuclease switches to the other DNA strand. (esrf.eu)
  • The enzyme binds to a free duplex end (a) and starts to unwind the DNA and digest the 3' strand (b). (esrf.eu)
  • Thus far, the connection between the gene, which produces a DNA-cutting enzyme called a nuclease, and the kidney disease has remained obscure. (medicalnewstoday.com)
  • Close observation of this miracle revealed that DNA synthesis was at work, in which each fragment serves as a template and extends itself by removing damaged ends and overlapping with a fragment that matches part of its sequence of nucleotides--all with the help of an enzyme known as PolA. (scientificamerican.com)
  • 1993) Yeast open reading frame YCR14C encodes a DNA beta‐polymerase‐like enzyme. (els.net)
  • The enzyme apurinic/apyrimidic endonuclease 1 (APE1) cleaves the abasic DNA strand. (els.net)
  • The enzyme poly(ADP‐ribose) polymerase (PARP) recognizes DNA damage caused by exogenous molecules and oxidative stress and signals for DNA repair. (els.net)
  • During the MMR process, which occurs in cells throughout the animal and plant kingdom, an enzyme repairs parts of DNA that have been copied incorrectly during cell replication. (wn.com)
  • A defective gene triggers the new disorder by boosting activity of a DNA-repair enzyme called PARP1. (belfasttelegraph.co.uk)
  • Scientists at The University of Texas MD Anderson Cancer Center reported their findings about the role of the enzyme fumarase in DNA repair in the Aug. 3, 2015 issue of Nature Cell Biology . (mdanderson.org)
  • Our study showed that the enzymatic activity of the metabolic enzyme fumarase and its product, fumarate, are critical elements of the DNA damage response and that fumarase deficiency promotes tumor growth due to impairment of DNA repair," said Zhimin Lu, M.D., Ph.D. , professor of Neuro-Oncology . (mdanderson.org)
  • In this issue of PLOS Genetics , two complementary papers establish a key function of ataxin-3 through its interaction with the DNA end-processing enzyme polynucleotide kinase 3′-phosphatase (PNKP) and reveal how this interplay contributes to SCA3 pathogenesis [ 6 , 7 ]. (plos.org)
  • DNA encodes the cell genome and is therefore a permanent copy of a structure necessary for the correct functioning of a cell. (news-medical.net)
  • The team confirmed that the failed genome repair and resulting catastrophic chromosomal events also apply to melanoma, brain tumors and breast cancer in humans and that the Myc oncogene is again involved. (news-medical.net)
  • This breakthrough, which involves hybrid nanomaterials and small angle X-ray scattering (SAXS) technology, has been used to solve a major problem involving genome integrity and the biological detection of mismatched DNA. (redorbit.com)
  • Now, researchers at the Salk Institute report which genes are turned on or off, and in which order, to orchestrate the cellular processes required to protect and repair the genome in response to DNA damage. (eurekalert.org)
  • This paper brings us one step closer to understanding how the response to DNA damage is coordinated over time to maintain genome stability. (eurekalert.org)
  • In addition to informing strategies to improve crop health by maintaining genome stability, this work may also shed light on conserved aspects of the DNA damage response in other organisms, as there are many parallels between SOG1 and a gene in animals that has a similar "general contractor" function--the p53 gene, a tumor suppressor known for its role in combating DNA damage to prevent cancer. (eurekalert.org)
  • According to a new study led by Brigham and Women's Hospital and the Broad Institute of MIT and Harvard, CRISPR-Cas9 is capable precise genome editing-even without the assistance of donor DNA templates. (genengnews.com)
  • DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome . (bionity.com)
  • The DNA repair ability of a cell is vital to the integrity of its genome and thus to its normal functioning and that of the organism. (bionity.com)
  • 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)
  • Does this connection between defective genome repair and chromosome chaos also apply to human cancers? (eurekalert.org)
  • NER occurring in DNA that is not undergoing transcription (i.e., most of the genome) is called global genome repair (GGR or GGNER), while NER taking place in the transcribed strand of active genes is called transcription-coupled repair (TCR or TC-NER). (unt.edu)
  • It took a long time for me to accept this," said Dr. Michela Di Virgilio, head of the MDC Laboratory for DNA Repair and Maintenance of Genome Stability and junior professor at the Charité. (mdc-berlin.de)
  • The importance of DNA repair is also demonstrated by the increased rate of mutation that follows the inactivation of a DNA repair gene . (nih.gov)
  • Thus, we saw previously that defects in a human gene that normally functions to repair the mismatched base pairs in DNA resulting from replication errors can lead to an inherited predisposition to certain cancers, reflecting an increased mutation rate . (nih.gov)
  • To restore gene function without templated repair requires knowing how the cell will fix CRISPR-induced DNA breaks-knowledge that did not exist until now. (mit.edu)
  • After observing how the cell repaired those cuts, they poured the resulting data into a machine-learning model, inDelphi, prompting the algorithm to learn how the cell responded to cuts at each site - that is, which bits of DNA the cell added to or removed from each damaged gene. (mit.edu)
  • To better understand the dynamics of gene regulation throughout the DNA damage response and to determine the direct roles of SOG1 in this response, Law and her team conducted a series of experiments in Arabidopsis thaliana , a weed commonly used for genetics research. (eurekalert.org)
  • It's exciting to get more clarity on the specific gene networks and subnetworks involved in the DNA damage response, as well as their timing, which had not been done before," says Law. (eurekalert.org)
  • Davis, L. & Maizels, N. DNA nicks promote efficient and safe targeted gene correction. (nature.com)
  • In 2002, Strahl found that Set2 in yeast played a role as an off switch in gene expression - particularly when DNA is copied to make RNA. (newswise.com)
  • Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response. (nature.com)
  • Jan 21, 2003 - Tues 12:30PM - Dr. Jack Taylor, NIEHS - Epidemiologic studies of DNA repair gene polymorphisms and cancer risk Dec 17, 2002 - Dr. John Tainer, UC Berkeley - Conformational Controls and DNA Repair Coordination - [Note: The posting of this talk will be delayed at the request of the speaker. (bio.net)
  • Effects of aging on gene specific repair (A. Richardson, ZhongMao Guo). (elsevier.com)
  • The main functions of chromatin include packaging of DNA into a compact shape, reinforcement of the DNA molecules in such a way to allow the process of mitosis and controlling gene expression and DNA replication. (intechopen.com)
  • In cooperation with University Hospital Zurich, a study is already underway that involves examining samples of different types of cancer for the repair gene and its regulation. (medicalxpress.com)
  • the group demonstrated that alteration of key amino acid side chains cripples Pol β so that it no longer catalyzes DNA synthesis efficiently and does not discriminate between correct and incorrect incoming nucleotides. (nih.gov)
  • The non-defective strand is used as a template with the damaged DNA on the other strand removed and replaced by the synthesis of new nucleotides. (news-medical.net)
  • Lagging strand synthesis is more complex because of the requirement for DNA replication to take place in the 5' to 3' direction. (sparknotes.com)
  • DNA synthesis errors associated with double-strand-break repair. (genetics.org)
  • http://www.nih.gov:80/sigs/dna-rep/ ] Note: The Videoconferences will be taking a vacation in July and Aug. 1.1.1 FUTURE VIDEOCONFERENCES: Sept 16, 2003 - Tues - 12:30 PM - Dr. Satya Prakash - Translesion synthesis DNA polymerases of yeast and humans 1.1.2 VIDEOARCHIVES: INTERNET ACCESS (WORLDWIDE): To date 56 of these videoconferences have been archived and are available for viewing at your leisure on the internet. (bio.net)
  • The process--dubbed extended synthesis-dependent strand annealing--solves the mystery of how D. radiodurans survives radiation and repairs the damage it causes, according to the paper presenting the result published online in Nature on September 28. (scientificamerican.com)
  • When a replication fork encounters a DPC, the DPC is degraded into a peptide-adduct, which allows replication bypass by translesion DNA synthesis. (europa.eu)
  • During DNA synthesis the newly synthesised (daughter) strand will commonly include errors. (wikipedia.org)
  • Editing genes with CRISPR-Cas9 allows scientists to break DNA at specific locations, but this can create "spelling errors" that alter the function of genes. (mit.edu)
  • Scientists have known for decades that DNA can be damaged by too much sun (UV radiation) or exposure to harmful chemicals and carcinogens. (icr.org)
  • Three scientists whose work greatly advanced our understanding of DNA repair have won the 2015 Nobel Prize in Chemistry. (mentalfloss.com)
  • Scientists used to believe that DNA was constant and unchanging. (mentalfloss.com)
  • In clinical trials aimed at disrupting the DNA-repair process, scientists are using inhibitor drugs to block cdk signaling. (scienceblog.com)
  • In recent years, scientists have discovered the importance of how DNA is packaged inside nuclei. (newswise.com)
  • Nanowerk News ) Osaka University scientists, in collaboration with The University of Tokyo, describe the crystal structure of RNF168 bound to ubiquitin chains, a crucial interaction for DNA repair, to find a unique interaction ( Nature Communications , 'Structural insights into two distinct binding modules for Lys63-linked polyubiquitin chains in RNF168' ). (nanowerk.com)
  • The findings could aid research into other diseases related to DNA repair, say scientists. (belfasttelegraph.co.uk)
  • A LINK between the level of active DNA repair genes in melanoma tumours and the effectiveness of chemotherapy for skin cancer patients has been established for the first time by a team of scientists. (cancerresearchuk.org)
  • The idea of repair didn't occur to them, because it wasn't thought to be necessary," says Hanawalt. (newscientist.com)
  • However, ploidy changes occur in every sexual cycle of all eukaryotes and are associated with the inclusion or exclusion of an entire set of chromosome homologs that significantly alters the DNA repair capacity. (genetics.org)
  • Paul Modrich's contribution was on yet another type of DNA repair, this time correcting base-pair mismatches that inevitably occur during replication. (sciencemag.org)
  • These breaks can, for instance, be caused by ultraviolet light or X-rays, but also occur during cell division, when DNA molecules split and form two new DNA molecules. (innovations-report.com)
  • Once DNA breaks occur, they can eventually lead to tumors if unrepaired. (businesswire.com)
  • We found that if Set2 is mutated, DNA repair does not properly occur" said Strahl, professor of biochemistry and biophysics. (newswise.com)
  • This phenomenon, called karyomegaly, has also been seen in patients with karyomegalic interstitial nephritis, and it's thought to occur because the DNA duplicates too many times. (medicalnewstoday.com)
  • DNA is a two-stranded molecule, and breaks can occur to one strand of the molecule or to both. (rochester.edu)
  • That view still prevailed when Watson and Crick worked out the structure of the DNA molecule. (newscientist.com)
  • Neither Mendel nor Charles Darwin knew anything about the incredible molecule of life, DNA. (icr.org)
  • Now a U.S.C. Dornsife study reveals a molecule that "walks" damaged DNA to a kind of emergency room in the cell. (icr.org)
  • Once DNA was identified as the molecule of heredity (which was well before Watson and Crick famously worked out its structure), it was clear that it somehow had to be an unusually conserved substance. (sciencemag.org)
  • So one thought was that DNA must be an exceptionally stable molecule, that evolution had ended up selecting it for just that reason. (sciencemag.org)
  • They observed this at the level of a single DNA molecule. (innovations-report.com)
  • To observe this, a DNA molecule is stretched between a magnetic bead and a glass surface. (innovations-report.com)
  • In either case, a small‐molecule inhibitor of PARP can lead to an apoptotic cell death by shutting down DNA metabolism (but not glycolytic metabolism). (els.net)
  • In the case of single-strand breaks, the unbroken strand guides the repair process and the DNA molecule is typically restored to its original state. (rochester.edu)
  • They found the expression of approximately 2,400 genes went up or down in response to DNA damage during that time period, almost all of which depended on SOG1's presence. (eurekalert.org)
  • This resulted in the identification of 11 groups of genes that act on different time scales and play known or predicted roles in different aspects of the plants' response to DNA damage. (eurekalert.org)
  • Just as your smartphone might amend a misspelled text message into an incoherent phrase, the cell's natural DNA repair process can add or remove bits of DNA at the break site in a seemingly random and unpredictable manner. (mit.edu)
  • If DNA damage is not recognized and repaired in time then it can lead to any type of cancer. (redorbit.com)
  • if they are not repaired, they will cause cancer and aging. (elpasotimes.com)
  • Professor James Fleet of Purdue University and his colleagues authored an excellent detailed review of how vitamin D helps prevent cancer and he almost offhandedly mentioned DNA repair as one of vitamin D's mechanisms of action in cancer. (vitamindcouncil.org)
  • First the authors compared the abasic site repair activity in human lung cancer cell lines and found that there was an inverse correlation between the repair activity and the abundance of Bcl2. (sciencemag.org)
  • However, dysregulation of DNA damage sensing can also yield an increased mutation rate, potentially causing uncontrolled cell growth and cancer. (qiagen.com)
  • Colon cancer and DNA repair: have mismatches met their match? (ebi.ac.uk)
  • The finding, published online June 9 in the journal Nature Communications , is the first to show Set2's role in DNA repair and paves the way for further inquiry and targeted approaches to treating cancer patients. (newswise.com)
  • SETD2 plays such a critical role in DNA transcription and repair that Strahl is now teaming up with fellow UNC Lineberger Comprehensive Cancer Center members Stephen Frye, PhD, director of the UNC Center for Integrative Chemical Biology and Drug Discovery (CICBDD), Jian Jin, PhD, also with the CICBDD, and Kim Rathmell, MD, PhD, an associate professor in the department of genetics. (newswise.com)
  • The study, part-funded by Cancer Research UK and published in Clinical Cancer Research * today (Friday), found that higher levels of DNA repair genes in melanoma tumours were associated with a poorer response to chemotherapy. (cancerresearchuk.org)
  • A common class of chemicals found everywhere from car exhausts, smoke, building materials and furniture to cosmetics and shampoos could increase cancer risk because of their ability to break down the repair mechanisms that prevent faults in our genes, according to a study published today in the journal Cell . (cam.ac.uk)
  • This new research shows that aldehyde accumulation in such people could trigger cancer susceptibility by degrading BRCA2, compromising DNA repair, whether or not they inherit a faulty copy of BRCA2. (cam.ac.uk)
  • Methylation of guanine bases produces a change in the structure of DNA by forming a product that is complimentary to thymine rather than cytosine. (news-medical.net)
  • Similarly, a spontaneous deamination of cytosine to uracil in DNA occurs at a rate of about 100 bases per cell per day ( Figure 5-47 ). (nih.gov)
  • DNA bases are also occasionally damaged by an encounter with reactive metabolites (including reactive forms of oxygen) or environmental chemicals. (nih.gov)
  • Likewise, ultraviolet radiation from the sun can produce a covalent linkage between two adjacent pyrimidine bases in DNA to form, for example, thymine dimers ( Figure 5-48 ). (nih.gov)
  • The replication of damaged DNA before cell division can lead to the incorporation of wrong bases opposite damaged ones. (bionity.com)
  • When an adenosine in NEIL1 messenger RNA gets deaminated to form inosine, the mRNA is subsequently translated to place an arginine instead of a lysine in the portion of NEIL1 that recognizes oxidized DNA bases. (acs.org)
  • This handles less obvious problems than thymine dimers (which create an obvious lump in the DNA strand), going after individual DNA bases that have been alkylated, oxidized, or have lost an amino group. (sciencemag.org)
  • 1. A nucleic acid comprising a sequence at least 18 bases in length of a segment of the chemically pretreated DNA of genes associated with DNA repair according to one of the sequences taken from the group of Seq. (google.com.au)
  • Examples of mismatched bases include a G/T or A/C pairing (see DNA repair). (wikipedia.org)
  • Mismatches are commonly due to tautomerization of bases during DNA replication. (wikipedia.org)
  • Our study found that the increased expression of DNA repair genes in melanomas predict poorer outcome overall and provide preliminary evidence that those patients whose tumours have lower levels of the genes may respond better to standard chemotherapy for melanoma. (cancerresearchuk.org)
  • We postulate that the peripubertal IGF-1 surge, through epigenetic regulation, elicits persistent changes in expression of DNA repair genes. (ouhsc.edu)
  • A wealth of experimental data has established that DNA CT is exquisitely sensitive to even subtle perturbations in the base pair π-stack, including single base mismatches ( 3 , 8 , 9 ). (pnas.org)
  • In certain types of cancers, the repair process for DSBs go awry. (brandeis.edu)
  • Double-strand breaks (DSBs) are especially devastating since by definition there is no intact complementary strand to serve as a template for repair, and even one unrepaired DSB can be lethal . (unt.edu)
  • This year's Nobel Prize in Chemistry goes to Tomas Lindahl of the Crick Institute, Paul Modrich of Duke/Howard Hughes Medical Institue and Aziz Sancar of UNC - Chapel Hill, for mechanisms of DNA repair. (sciencemag.org)
  • Biochemical ( 16 ) and structural ( 17 , 18 ) evidence indicates that, upon photolyase binding, the pyrimidine dimer is flipped out of the DNA helix into a pocket accessible to the flavin cofactor. (pnas.org)
  • Gathering meaningful biochemical data, including high-quality DNA sequence information, from these samples reproducibly poses a challenge. (neb.com)
  • Samuel H. Wilson heads the DNA Repair and Nucleic Acid Enzymology Group and holds a secondary appointment in the NIEHS Epigenetics and Stem Cell Biology Laboratory . (nih.gov)
  • To define the biological role of DNA polymerase beta, the group and collaborators constructed DNA polymerase "knock-out" cell lines from a transgenic mouse model. (nih.gov)
  • If you can correct your DNA at every cell in your body. (bibliotecapleyades.net)
  • But that frequency in fact is where everything is and that frequency just happens to interact with the DNA in the cell. (bibliotecapleyades.net)
  • In this process, the cell attempts to repair damaged DNA by locating and copying a donor sequence, a nearly identical copy that is used to patch up the broken chromosome. (brandeis.edu)
  • We constructed a library of 2,000 Cas9 guide RNAs paired with DNA target sites and trained inDelphi, a machine learning model that predicts genotypes and frequencies of 1- to 60-base-pair deletions and 1-base-pair insertions with high accuracy (r = 0.87) in five human and mouse cell lines," the authors of the Nature article wrote. (genengnews.com)
  • ATM is a master regulator of DNA repair and cell division. (cincinnatichildrens.org)
  • The virus DNA is present in the latently infected cell nucleus, but there is little DNA replication and only minimal expression of virus-encoded genes. (hindawi.com)
  • Dr Camilla Sjögren and her research team have now shown that the cell also employs cohesion to repair damaged sister chromatids. (eurekalert.org)
  • Their results show that DNA damage can reactivate cohesin, which runs counter to the commonly held view that cohesion only arises during the DNA copying that takes place before cell division. (eurekalert.org)
  • The rate of DNA repair is dependent on many factors, including the cell type, the age of the cell, and the extracellular environment. (bionity.com)
  • The nucleus of a cell can be divided into functional compartments based on transcriptional activity and DNA replication. (sciencemag.org)
  • Outside the cell, isolated DNA was very easy to degrade (a vigorous stirring would break it into pieces). (sciencemag.org)
  • Every human cell contains roughly two meters' worth of DNA. (asbmb.org)
  • If this type of break is not properly repaired it can be highly dangerous to the functioning of the cell and lead to the creation of a cancerous cell. (innovations-report.com)
  • When a cell senses damage to its DNA, it triggers a series of events, called a "checkpoint cascade. (scienceblog.com)
  • Fortunately, in most cases the cell not only detects the break, but repairs it more cleanly than you can patch a tire. (extremetech.com)
  • Yu, X. & Chen, J. DNA damage-induced cell cycle checkpoint control requires CtIP, a phosphorylation-dependent binding partner of BRCA1 C-terminal domains. (nature.com)
  • DNA instability, telomere dynamics, and cell transformation (R.J. Shmookler Reis, M.A. Shammas). (elsevier.com)
  • The presence of these complexes in the cell and their functional role are systematically addressed through collaboration with cell biologists working on DNA damage signaling and repair and nuclear organization. (cea.fr)
  • For starters, DNA dictates the formation of every cell in your body. (skininc.com)
  • Most importantly to survival, if DNA is severely damaged, then a cell can become cancerous and thereby lethal. (skininc.com)
  • A CHO-cell strain having hypersensitivity to mutagens, a defect in DNA strand-break repair, and an extraordinary baseline frequency of sister-chromatid exchange. (atcc.org)
  • Maladaptive proximal tubule (PT) repair has been implicated in kidney fibrosis through induction of cell-cycle arrest at G2/M. We explored the relative importance of the PT DNA damage response (DDR) in kidney fibrosis by genetically inactivating ataxia telangiectasia and Rad3-related (ATR), which is a sensor and upstream initiator of the DDR. (jci.org)
  • The findings, combined with earlier, published work that visualized MMR in a living cell for the first time, more fully explains how eukaryotes eliminate DNA replication errors, which can result in defects and the development of cancers. (ucsd.edu)
  • The DNA damage response is a routine event in the life of any cell. (science20.com)
  • But in this case, the cell is breaking its DNA on purpose for the benefit of immunity. (mdc-berlin.de)
  • DNA chains are made of four precise chemical base pairs with distinct compositions. (redorbit.com)
  • If left uncorrected when the DNA is replicated, most of these changes would be expected to lead either to the deletion of one or more base pairs or to a base-pair substitution in the daughter DNA chain ( Figure 5-49 ). (nih.gov)
  • In contrast, particular kinds of mismatched base pairs are repaired through very short-patch MMR in which a short oligonucleotide tract is excised to remove the lesion [ 11 - 13 ]. (hindawi.com)
  • It involves the correction of mismatched base pairs that have been missed by the proofreading element of the DNA polymerase complex. (ebi.ac.uk)
  • Despite this, the DNA substrate has been partially unwound, with four base-pairs of the duplex split. (esrf.eu)
  • A few or up to thousands of base pairs of the newly synthesized DNA strand can be removed. (wikipedia.org)
  • When bound, the MutS2 dimer bends the DNA helix and shields approximately 20 base pairs. (wikipedia.org)
  • Photolyase is a light-activated flavoenzyme that binds to pyrimidine dimers in DNA and repairs them in a reaction triggered by electron transfer from the photoexcited flavin cofactor to the dimer. (pnas.org)
  • The assembly of MMRS is initiated by MutS, which recognises and binds to mispaired nucleotides and allows further action of MutL and MutH to eliminate a portion of newly synthesized DNA strand containing the mispaired base [ PMID: 17599803 ]. (ebi.ac.uk)
  • MutS forms a dimer (MutS2) that recognises the mismatched base on the daughter strand and binds the mutated DNA. (wikipedia.org)
  • MutH binds at hemimethylated sites along the daughter DNA, but its action is latent, being activated only upon contact by a MutL dimer (MutL2), which binds the MutS-DNA complex and acts as a mediator between MutS2 and MutH, activating the latter. (wikipedia.org)
  • Nearly 99.9% of typical, daily DNA damage is repaired because of the remarkable work of a healthy immune system, but the esthetic methods listed above create much more harm than the skin can handle. (skininc.com)
  • Frederick AM, Davis ML and Rice KP (2009) Inhibition of human DNA polymerase beta activity by the anticancer prodrug Cloretazine. (els.net)
  • While these investigations of the biological effects of intense THz pulses are only just beginning," said Lyubov Titova, with the University of Alberta and a member of the research team, "the fact that intense THz pulses can induce DNA damage but also DNA repair mechanisms in human skin tissue suggests that intense THz pulses need to be evaluated for possible therapeutic applications. (businesswire.com)