An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.
An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.
Lack of stability of a joint or joint prosthesis. Factors involved are intra-articular disease and integrity of extra-articular structures such as joint capsule, ligaments, and muscles.
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.
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.
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.
Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
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.
A method for comparing two sets of chromosomal DNA by analyzing differences in the copy number and location of specific sequences. It is used to look for large sequence changes such as deletions, duplications, amplifications, or translocations.
The occurrence of highly polymorphic mono- and dinucleotide MICROSATELLITE REPEATS in somatic cells. It is a form of genome instability associated with defects in DNA MISMATCH REPAIR.
The chemical and physical integrity of a pharmaceutical product.
Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.
The process by which a DNA molecule is duplicated.
Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.
A 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).
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.
An autosomal recessive disorder characterized by telangiectatic ERYTHEMA of the face, photosensitivity, DWARFISM and other abnormalities, and a predisposition toward developing cancer. The Bloom syndrome gene (BLM) encodes a RecQ-like DNA helicase.
The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.
The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. In a normally diploid cell (DIPLOIDY) the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is MONOSOMY (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is TRISOMY (symbol: 2N+1).
A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).
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.
The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.
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.
An autosomal recessive disorder that causes premature aging in adults, characterized by sclerodermal skin changes, cataracts, subcutaneous calcification, muscular atrophy, a tendency to diabetes mellitus, aged appearance of the face, baldness, and a high incidence of neoplastic disease.
The systematic study of the complete DNA sequences (GENOME) of organisms.
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.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
The cell center, consisting of a pair of CENTRIOLES surrounded by a cloud of amorphous material called the pericentriolar region. During interphase, the centrosome nucleates microtubule outgrowth. The centrosome duplicates and, during mitosis, separates to form the two poles of the mitotic spindle (MITOTIC SPINDLE APPARATUS).
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.
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.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
The extent to which an enzyme retains its structural conformation or its activity when subjected to storage, isolation, and purification or various other physical or chemical manipulations, including proteolytic enzymes and heat.
A type of chromosomal aberration involving DNA BREAKS. Chromosome breakage can result in CHROMOSOMAL TRANSLOCATION; CHROMOSOME INVERSION; or SEQUENCE DELETION.
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.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.
A form of GENE LIBRARY containing the complete DNA sequences present in the genome of a given organism. It contrasts with a cDNA library which contains only sequences utilized in protein coding (lacking introns).
A Rec A recombinase found in eukaryotes. Rad51 is involved in DNA REPAIR of double-strand breaks.
The chromosomal constitution of a cell containing multiples of the normal number of CHROMOSOMES; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc.
The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.
Interruptions in the sugar-phosphate backbone of DNA.
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.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
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.
Established cell cultures that have the potential to propagate indefinitely.
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.
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.
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.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
DNA present in neoplastic tissue.
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.
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.
Distinct units in some bacterial, bacteriophage or plasmid GENOMES that are types of MOBILE GENETIC ELEMENTS. Encoded in them are a variety of fitness conferring genes, such as VIRULENCE FACTORS (in "pathogenicity islands or islets"), ANTIBIOTIC RESISTANCE genes, or genes required for SYMBIOSIS (in "symbiosis islands or islets"). They range in size from 10 - 500 kilobases, and their GC CONTENT and CODON usage differ from the rest of the genome. They typically contain an INTEGRASE gene, although in some cases this gene has been deleted resulting in "anchored genomic islands".
An exchange of DNA between matching or similar sequences.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
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.
The extent to which an RNA molecule retains its structural integrity and resists degradation by RNASE, and base-catalyzed HYDROLYSIS, under changing in vivo or in vitro conditions.
The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair, resulting in abnormal HEMIZYGOSITY. It is detected when heterozygous markers for a locus appear monomorphic because one of the ALLELES was deleted.
The number of copies of a given gene present in the cell of an organism. An increase in gene dosage (by GENE DUPLICATION for example) can result in higher levels of gene product formation. GENE DOSAGE COMPENSATION mechanisms result in adjustments to the level GENE EXPRESSION when there are changes or differences in gene dosage.
Mapping of the KARYOTYPE of a cell.
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.
In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Very long DNA molecules and associated proteins, HISTONES, and non-histone chromosomal proteins (CHROMOSOMAL PROTEINS, NON-HISTONE). Normally 46 chromosomes, including two sex chromosomes are found in the nucleus of human cells. They carry the hereditary information of the individual.
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.
Any method used for determining the location of and relative distances between genes on a chromosome.
A cell line derived from cultured tumor cells.
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).
Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.
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.
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)
The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)
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.
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.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Defective nuclei produced during the TELOPHASE of MITOSIS or MEIOSIS by lagging CHROMOSOMES or chromosome fragments derived from spontaneous or experimentally induced chromosomal structural changes.
The 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)
Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.
The relationships of groups of organisms as reflected by their genetic makeup.
A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication.
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.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
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.
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.
The decrease in the cell's ability to proliferate with the passing of time. Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS.
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.
The repair of DOUBLE-STRAND DNA BREAKS by rejoining the broken ends of DNA to each other directly.
Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.
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.
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.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
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.
An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.
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.
Changes in the organism associated with senescence, occurring at an accelerated rate.
The variable phenotypic expression of a GENE depending on whether it is of paternal or maternal origin, which is a function of the DNA METHYLATION pattern. Imprinted regions are observed to be more methylated and less transcriptionally active. (Segen, Dictionary of Modern Medicine, 1992)
The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.
A DNA-binding protein that mediates DNA REPAIR of double strand breaks, and HOMOLOGOUS RECOMBINATION.
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.
Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.
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).
A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.
The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.
The genetic complement of a BACTERIA as represented in its DNA.
Stretches of genomic DNA that exist in different multiples between individuals. Many copy number variations have been associated with susceptibility or resistance to disease.
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.
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.
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.
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)
Genotypic differences observed among individuals in a population.
Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).
A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.
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)
Mad2 is a component of the spindle-assembly checkpoint apparatus. It binds to and inhibits the Cdc20 activator subunit of the anaphase-promoting complex, preventing the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. Mad2 is required for proper microtubule capture at KINETOCHORES.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
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.
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.
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.
The act of ligating UBIQUITINS to PROTEINS to form ubiquitin-protein ligase complexes to label proteins for transport to the PROTEASOME ENDOPEPTIDASE COMPLEX where proteolysis occurs.
The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
A large, nuclear protein, encoded by the BRCA2 gene (GENE, BRCA2). Mutations in this gene predispose humans to breast and ovarian cancer. The BRCA2 protein is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev. 2000;14(11):1400-6)
A microtubule structure that forms during CELL DIVISION. It consists of two SPINDLE POLES, and sets of MICROTUBULES that may include the astral microtubules, the polar microtubules, and the kinetochore microtubules.
Deletion of sequences of nucleic acids from the genetic material of an individual.
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.
Highly repetitive DNA sequences found in HETEROCHROMATIN, mainly near centromeres. They are composed of simple sequences (very short) (see MINISATELLITE REPEATS) repeated in tandem many times to form large blocks of sequence. Additionally, following the accumulation of mutations, these blocks of repeats have been repeated in tandem themselves. The degree of repetition is on the order of 1000 to 10 million at each locus. Loci are few, usually one or two per chromosome. They were called satellites since in density gradients, they often sediment as distinct, satellite bands separate from the bulk of genomic DNA owing to a distinct BASE COMPOSITION.
A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.
A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
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.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Elements of limited time intervals, contributing to particular results or situations.
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.
The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Regulatory signaling systems that control the progression through the CELL CYCLE. They ensure that the cell has completed, in the correct order and without mistakes, all the processes required to replicate the GENOME and CYTOPLASM, and divide them equally between two daughter cells. If cells sense they have not completed these processes or that the environment does not have the nutrients and growth hormones in place to proceed, then the cells are restrained (or "arrested") until the processes are completed and growth conditions are suitable.
A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
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).
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
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.
Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.
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.
Interruption or suppression of the expression of a gene at transcriptional or translational levels.
DNA constructs that are composed of, at least, a REPLICATION ORIGIN, for successful replication, propagation to and maintenance as an extra chromosome in bacteria. In addition, they can carry large amounts (about 200 kilobases) of other sequence for a variety of bioengineering purposes.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Transport proteins that carry specific substances in the blood or across cell membranes.
A homologous family of regulatory enzymes that are structurally related to the protein silent mating type information regulator 2 (Sir2) found in Saccharomyces cerevisiae. Sirtuins contain a central catalytic core region which binds NAD. Several of the sirtuins utilize NAD to deacetylate proteins such as HISTONES and are categorized as GROUP III HISTONE DEACETYLASES. Several other sirtuin members utilize NAD to transfer ADP-RIBOSE to proteins and are categorized as MONO ADP-RIBOSE TRANSFERASES, while a third group of sirtuins appears to have both deacetylase and ADP ribose transferase activities.
Chromic acid (H2Cr2O7), dipotassium salt. A compound having bright orange-red crystals and used in dyeing, staining, tanning leather, as bleach, oxidizer, depolarizer for dry cells, etc. Medically it has been used externally as an astringent, antiseptic, and caustic. When taken internally, it is a corrosive poison.
Immunologically detectable substances found in the CELL NUCLEUS.
A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.
A situation where one member (allele) of a gene pair is lost (LOSS OF HETEROZYGOSITY) or amplified.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Tumors or cancer of the human BREAST.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.
The complete gene complement contained in a set of chromosomes in a fungus.
The phase of cell nucleus division following PROMETAPHASE, in which the CHROMOSOMES line up across the equatorial plane of the SPINDLE APPARATUS prior to separation.
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.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Actual loss of portion of a chromosome.
Deoxyribonucleic acid that makes up the genetic material of fungi.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
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.
Biochemical identification of mutational changes in a nucleotide sequence.
A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)
The complete genetic complement contained in a DNA or RNA molecule in a virus.
A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.
Highly repeated sequences, 6K-8K base pairs in length, which contain RNA polymerase II promoters. They also have an open reading frame that is related to the reverse transcriptase of retroviruses but they do not contain LTRs (long terminal repeats). Copies of the LINE 1 (L1) family form about 15% of the human genome. The jockey elements of Drosophila are LINEs.
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.
Interruptions in one of the strands of the sugar-phosphate backbone of double-stranded DNA.
An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.
The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.
Deoxyribonucleic acid that makes up the genetic material of bacteria.
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.
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.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
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.
A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets.
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.-.
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.-.
Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.
An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA.
Specific loci that show up during KARYOTYPING as a gap (an uncondensed stretch in closer views) on a CHROMATID arm after culturing cells under specific conditions. These sites are associated with an increase in CHROMOSOME FRAGILITY. They are classified as common or rare, and by the specific culture conditions under which they develop. Fragile site loci are named by the letters "FRA" followed by a designation for the specific chromosome, and a letter which refers to which fragile site of that chromosome (e.g. FRAXA refers to fragile site A on the X chromosome. It is a rare, folic acid-sensitive fragile site associated with FRAGILE X SYNDROME.)
A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.
Low-copy (2-50) repetitive DNA elements that are highly homologous and range in size from 1000 to 400,000 base pairs.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.
Induction and quantitative measurement of chromosomal damage leading to the formation of micronuclei (MICRONUCLEI, CHROMOSOME-DEFECTIVE) in cells which have been exposed to genotoxic agents or IONIZING RADIATION.
A subunit of the anaphase-promoting complex whose primary function is to provide structural support for the catalytic and substrate-recognition modules of the complex. Apc5, along with Apc4, tethers the tetratricopeptide-coactivator binding subcomplex to the main structural subunit, Apc1.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
CK1δ is involved in microtubule dynamics, cell cycle progression, genomic stability, mitosis and meiosis. Transient mitotic ... Absence of CK1δ has been also associated with genomic instability. Nevertheless, the role of CK1δ in mitosis is still unclear ... Greer YE, Gao B, Yang Y, Nussenzweig A, Rubin JS (2017). "Lack of Casein Kinase 1 Delta Promotes Genomic Instability - the ... Treatment of cancer cells with peptide δ-361 finally resulted to microtubule destabilization and cell death. Fine-mapping of ...
It is ideal to use a fosmid library because of its stability and limitation of one plasmid per cell. By limiting the number of ... coli cells. Therefore, Fosmids serve as reliable substrates for large scale genomic DNA sequencing. Hall BG (May 2004). " ... Highly repetitive in nature, human DNA is well known for its extreme instability in multicopy vector systems. It has been found ... Conjugation involves using the sex pilus to form a bridge between two bacteria cells; the bridge allows the F+ cell to transfer ...
... leading to high genomic instability. Disruption of Chk1 in mice led significant misregulation of cell cycle checkpoints, an ... and cell cycle checkpoints have been intimately linked with cancer due to their functions regulating genome stability and cell ... During this process, known as the cell cycle, a cell duplicates its contents and then divides in two. The purpose of the cell ... After the cell has split into its two daughter cells, the cell enters G1. DNA repair processes ...
Cyclin F interacts with RRM2 to control the production of dNTPs in the cell to avoid genomic instability and frequency of ... cyclin F controls genome stability through ubiquitin-mediated proteolysis". Trends in Cell Biology. 23 (3): 135-40. doi:10.1016 ... by allowing only one centrosome replication per cell cycle. NuSAP is a substrate of cyclin F that is involved in cell division ... Cell. 147 (2): 459-74. doi:10.1016/j.cell.2011.09.019. PMC 3226719. PMID 21963094. Ribbeck K, Groen AC, Santarella R, Bohnsack ...
Genomic instability has been observed both in vitro and in vivo in the progeny of cells that are irradiated with heavy ions in ... Heavy-ion-induced effects on telomere stability have also been studied using siRNA (small interfering ribonucleic acid) ... Telomere dysfunction plays a crucial role in initiating or sustaining genomic instability, which is a major step in cancer ... thereby promoting genetic instability. The fate of normal cells that contain a single terminal deletion is unknown, but it has ...
If damaged DNA is left unrepaired, it can lead to cell death or genomic instability, cancer and other pathologies.[23] ... ATM kinase, a member of the PI3-like family of serine/threonine kinases plays a critical role in maintaining the stability of ... "Cell. 138 (3): 514-24. doi:10.1016/j.cell.2009.05.028. PMC 4764080. PMID 19665973.. ... Src kinases are involved in intracellular signaling pathways that influence cell growth and cell adhesion strength. The latter ...
... mutations in caretaker genes lead to genomic instability. Tumor cells arise from two distinct classes of genomic instability: ... In addition to providing genomic stability, caretakers also provide chromosomal stability. Chromosomal instability resulting ... Growth of cells depends both on cell-to-cell interactions and cell-to-extracellular matrix (ECM) interactions. Mechanisms of ... Rounds of cell replication allow fixation of mutated genes into the genome. Caretaker genes provide genome stability by ...
... plays a role in regulation or progression through the cell cycle, apoptosis, and genomic stability by means of several ... Loss of p53 creates genomic instability that most often results in an aneuploidy phenotype. Increasing the amount of p53 may ... Suppression of p53 plays important roles in cancer stem cell phenotype, induced pluripotent stem cells and other stem cell ... Tsai RY, McKay RD (December 2002). "A nucleolar mechanism controlling cell proliferation in stem cells and cancer cells". Genes ...
... cells of affected individuals exhibit chromosomal abnormalities, genomic instability, and sensitivity to mutagens.[7] ... genomic stability and aging". Biogerontology. 10 (3): 235-52. doi:10.1007/s10522-008-9205-z. PMC 2713741 . PMID 19083132.. ... "Genomic instability in laminopathy-based premature aging". Nat. Med. 11 (7): 780-5. doi:10.1038/nm1266. PMID 15980864.. ... A-type lamins promote genetic stability by maintaining levels of proteins which have key roles in NHEJ and HR.[77] Mouse cells ...
... and genomic instability in lymphocytes". The Journal of Experimental Medicine. 207 (6): 1145-52. doi:10.1084/jem.20091245. PMC ... "WASp-dependent actin cytoskeleton stability at the dendritic cell immunological synapse is required for extensive, functional T ... It contains 502 amino acids and is mainly expressed in hematopoietic cells (the cells in the bone marrow that develop into ... In T-cells, WASp is important because it is known to be activated via T-cell receptor signaling pathways to induce cortical ...
The clonal plasma cells involved in plasma cell dyscrasias exhibit a high degree of genetic instability. For example, the ... These genomic changes can go awry by placing a gene that controls cell growth an/or survival adjacent to a normally highly ... Genes affecting include those regulating genome stability itself (e.g. KIF2B) as well as cellular activation, proliferation, ... Plasma cell dyscrasias (also termed plasma cell disorders and plasma cell proliferative diseases) are a spectrum of ...
"Could MYC induction of mitochondrial biogenesis be linked to ROS production and genomic instability?". Cell Cycle. 4 (11): 1465 ... "Control of c-myc mRNA half-life in vitro by a protein capable of binding to a coding region stability determinant". Genes & ... cell cycle arrest. • positive regulation of response to DNA damage stimulus. • positive regulation of cell proliferation. • ... "Cell. 142 (3): 480-93. PMC 2923036 . PMID 20691906. doi:10.1016/j.cell.2010.06.037.. ...
"MDC1 maintains genomic stability by participating in the amplification of ATM-dependent DNA damage signals". Mol Cell. 21 (2): ... "MicroRNA-22 Suppresses DNA Repair and Promotes Genomic Instability through Targeting of MDC1". Cancer Research. 75 (7): 1298- ... and cell cycle alterations in NFBD1-depleted human esophageal cancer cells". Mol Cell Biochem. 342 (1-2): 1-6. doi:10.1007/ ... The DDR of mammalian cells is made up of kinases, and mediator/adaptors factors. In mammalian cells the DRR is a network of ...
In addition, increased genomic instability and tumorigenesis have been observed in Geminin knockout mice in both the colon and ... Since geminin knockdown leads to cell death in many cancer cell lines but not primary cell lines, it has been proposed as a ... while there is data demonstrating that Geminin acts as a tumor suppressor by safeguarding genome stability. GRCh38: Ensembl ... Collins FS, Rossant J, Wurst W (2007). "A mouse for all reasons". Cell. 128 (1): 9-13. doi:10.1016/j.cell.2006.12.018. PMID ...
... genomic instability, or both and by cancer predisposition. Cells from a person with Bloom syndrome exhibit a striking genomic ... The BLM protein is important in maintaining the stability of the DNA during the replication process. Lack of BLM protein or ... The cells from persons with Bloom syndrome exhibit a striking genomic instability that is characterized by hyper-recombination ... When a cell prepares to divide to form two cells, the chromosomes are duplicated so that each new cell will get a complete set ...
Deregulation of MCM function has been linked to genomic instability and a variety of carcinomas. The minichromosome maintenance ... Various MCMs have been shown to promote cell proliferation in vitro and in vivo especially in certain types of cancer cell ... Those that affected the stability of all minichromosomes and others that affected the stability of only a subset of the ... Cell. 161 (3): 513-525. doi:10.1016/j.cell.2015.03.012. PMC 4445235. PMID 25892223. Coster G, Diffley JF (July 2017). " ...
"Genomic instability and aging-like phenotype in the absence of mammalian SIRT6". Cell. 124 (2): 315-29. doi:10.1016/j.cell. ... genomic stability and aging". Biogerontology. 10 (3): 235-52. doi:10.1007/s10522-008-9205-z. PMC 2713741. PMID 19083132.. ... skin cancers (basal cell, squamous cell, melanoma) [64] mutS (E. coli) homolog 2, mutS (E. coli) homolog 6, mutL (E. coli) ... "Cell Stem Cell. 1 (1): 113-26. doi:10.1016/j.stem.2007.03.002. PMC 2920603. PMID 18371340.. ...
"Increased microsatellite instability and epigenetic inactivation of the hMLH1 gene in head and neck squamous cell carcinoma". ... "Modulation of mismatch repair and genomic stability by miR-155". Proc. Natl. Acad. Sci. U.S.A. 107 (15): 6982-7. Bibcode: ... Cell. 149 (2): 334-47. doi:10.1016/j.cell.2012.03.023. PMC 3377385. PMID 22500800. Lebrun C, Olschwang S, Jeannin S, Vandenbos ... those mismatches and repairing them is important for cells because failure to do so results in microsatellite instability] and ...
"Genomic instability in laminopathy-based premature aging". Nat. Med. 11 (7): 780-5. doi:10.1038/nm1266. PMID 15980864. Yozef ... A-type lamins promote genetic stability by maintaining levels of proteins that have key roles in NHEJ and HR. Mouse cells ... Molecular Biology of the Cell (4th edition). Garland Science 676-677 Geoffrey M. Cooper, Robert E. Hausman. The Cell, A ... cell cycle regulation, DNA replication, DNA repair, cell differentiation and apoptosis. The non-random organization of the ...
"Could MYC induction of mitochondrial biogenesis be linked to ROS production and genomic instability?". Cell Cycle 4 (11): 1465- ... "Control of c-myc mRNA half-life in vitro by a protein capable of binding to a coding region stability determinant". Genes Dev. ... Cell Genet. 57 (2-3): 109-11. PMID 1914517. doi:10.1159/000133124. CS1 održavanje: Eksplicitna upotreba et al. (link) ... Dang CV, O'donnell KA, Juopperi T (2005). "The great MYC escape in tumorigenesis". Cancer Cell 8 (3): 177-8. PMID 16169462. doi ...
Gaubatz JW (1990). "Extrachromosomal circular DNAs and genomic sequence plasticity in eukaryotic cells". Mutation Research. 237 ... Borghouts C, Benguria A, Wawryn J, Jazwinski SM (February 2004). "Rtg2 protein links metabolism and genome stability in yeast ... Strehler BL (1986-01-01). "Genetic instability as the primary cause of human aging". Experimental Gerontology. 21 (4-5): 283- ... Accumulated ERCs impair cell proliferation in old cells by interfering with the expression of important cell cycle genes at the ...
This generates genomic instability through increased inaccurate MMEJ DNA repair, and likely contributes to progression to ... Therefore, they are important control factors for protein levels and cell phenotypes. Moreover, they affect mRNA stability by ... mRNA Stability can be manipulated in order to control its half-life, and the poly(A) tail has some effect on this stability, as ... "Control of gene expression during T cell activation: alternate regulation of mRNA transcription and mRNA stability". BMC ...
Abbas T, Keaton MA, Dutta A (March 2013). "Genomic instability in cancer". Cold Spring Harbor Perspectives in Biology. 5 (3): ... Mapping origins in single cells in metazoan systems and correlating these initiation events with single-cell gene expression ... Yakovchuk P, Protozanova E, Frank-Kamenetskii MD (2006). "Base-stacking and base-pairing contributions into thermal stability ... Cell. 139 (4): 719-30. doi:10.1016/j.cell.2009.10.015. PMC 2804858. PMID 19896182. Evrin C, Clarke P, Zech J, Lurz R, Sun J, ...
December 2010). "KIAA1018/FAN1 nuclease protects cells against genomic instability induced by interstrand cross-linking agents ... Kee Y, D'Andrea AD (August 2010). "Expanded roles of the Fanconi anemia pathway in preserving genomic stability". Genes & ... June 2004). "Protein tyrosine phosphatases in the human genome". Cell. 117 (6): 699-711. doi:10.1016/j.cell.2004.05.018. PMID ... Cell. 142 (1): 65-76. doi:10.1016/j.cell.2010.06.021. PMC 3710700. PMID 20603015. Pennell S, Déclais AC, Li J, Haire LF, Berg W ...
On the cellular level, cells of affected individuals exhibit chromosomal abnormalities, genomic instability, and sensitivity to ... Singh, DK; Ahn, B; Bohr, VA (2009). "Roles of RECQ helicases in recombination based DNA repair, genomic stability and aging". ... Thus, individuals with RecQ-associated PS show an increased risk of developing cancer, which is caused by genomic instability ... Gordon, Leslie B.; Cao, Kan; Collins, Francis S. (2012). "Progeria: Translational insights from cell biology". J Cell Biol. 199 ...
... it has yet to be determined if it is the actual cause of the genomic instability observed in cells and the high rate of cancer ... The loss of the helicase activity can have far-reaching consequences in terms of cell stability and mutation. One instance of ... where WS cells become even more sensitive to agents that increase cell stress and agents that damage DNA. As a result, WS cells ... Crabbe L, Jauch A, Naeger CM, Holtgreve-Grez H, Karlseder J (2007). "Telomere dysfunction as a cause of genomic instability in ...
Patients also don't have appropriate DNA repair, and they also have increased genomic instability. In normal conditions, the ... A-type lamins promote genetic stability by maintaining levels of proteins that have key roles in NHEJ and HR. Mouse cells ... A study that compared HGPS patient cells with the skin cells from young and elderly normal human subjects found similar defects ... HPGS is caused by mutations that weaken the structure of the cell nucleus, making normal cell division difficult. The histone ...
"Could MYC induction of mitochondrial biogenesis be linked to ROS production and genomic instability?". Cell Cycle. 4 (11): 1465 ... "Control of c-myc mRNA half-life in vitro by a protein capable of binding to a coding region stability determinant". Genes & ... Myc genes play a number of normal roles in stem cells including pluripotent stem cells. In neural stem cells, N-Myc promotes a ... There have been several studies that have clearly indicated Myc's role in cell competition. A major effect of c-myc is B cell ...
... "outstanding contribution to defining the link between the basic mechanism of genomic DNA instability and its relationship to ... Jackson's work has also helped establish how DSB repair is controlled during the cell cycle, at telomeres in response to cell ... In 2017 he was awarded the Genome Stability Network medal for his contributions to the field of genome stability and ... Blackford AN, Jackson SP (2017). "ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response". Molecular Cell. ...
This paper describes modifications to standard culture conditions that permit the growth of naive human pluripotent stem cells ... The Genomic Health of Human Pluripotent Stem Cells: Genomic Instability and the Consequences on Nuclear Organization *Marianne ... Naive pluripotent stem cells derived directly from isolated cells of the human inner cell mass. Stem Cell Rep. 6, 437-446 (2016 ... Erk signaling is indispensable for genomic stability and self-renewal of mouse embryonic stem cells. Proc. Natl. Acad. Sci. USA ...
Genomic instability decreased thereafter over time. Nonrandom aneuploidy 12 weeks after infection showed clonal evolution in ... After 25 weeks post-infection, most cells exhibited karyotypic stability. Chromosomal aberrations were compatible with telomere ... Its ability to induce unlimited in vitro proliferation of B cells is frequently used to generate lymphoblastoid cell lines ( ... Chromosomal rearrangements after ex vivo Epstein-Barr virus (EBV) infection of human B cells.. Lacoste S1, Wiechec E, Dos ...
Genomic instability is a hallmark of cancer. Whether it also occurs in Cancer Associated Fibroblasts (CAFs) remains to be ... to a central role of CSL in telomere homeostasis with important implications for genomic instability of cancer stromal cells ... Genomic instability is a hallmark of cancer. Whether it also occurs in Cancer Associated Fibroblasts (CAFs) remains to be ... CSL controls telomere maintenance and genome stability in human dermal fibroblasts Nat Commun. 2019 Aug 29;10(1):3884. doi: ...
Indefinite proliferation of eukaryotic cells depends on telomerase that counteracts the depletion of DNA from chromosome ... Genomic Instability* * Genotype * Mitosis * Ploidies * Telomerase / deficiency * Telomerase / genetics * Telomerase / ... Genome stability in Arabidopsis cells exhibiting alternative lengthening of telomeres Cytogenet Genome Res. 2008;122(3-4):388- ... ALT activation increases karyotype stability in the majority of tert ku70 cell lines, which contrasts with ongoing chromosomal ...
Its role within the cell is to link chromatin silencing to genomic stability, cellular metabolism, and lifespan regulation. ... First, telomere structures need to be correct in order to maintain genomic stability; chromosomal instability is apparent in ... For example, in mice, if there is a deficiency for SIRT6 (family member of Sir2), the mice experience genomic instability, ... For example,Sir2 asymmetrically segregates damaged proteins to the yeast mother cell during cell division; this asymmetry can ...
Gadd45a is a p53-regulated gene whose protein product, like p53, is involved in maintenance of genome stability. Specifically, ... Genomic instability in Gadd45a-/- cells is coupled with S-phase checkpoint defects.. Hollander MC1, Philburn RT, Patterson AD, ... Gadd45a deletion allows another form of genomic instability, gene amplification, when p21 (Cdkn1a gene product) is deleted also ... which may lack sufficient nutrients yet are unable to elicit checkpoints preventing genomic instability under these conditions. ...
... in another clear cell renal cell carcinoma (ccRCC) cohort E-GEOD-22541 (n = 44, 390.0 versus 1889.2 days, p = 0.0007), and in a ... which could effectively predict the overall survival in a TCGA clear cell RCC cohort (n = 533, 995.3 versus 2242.2 days, p , ... combination of low CD151 expression and high RNASEH2A expression resulted in impaired proliferation in four kidney cancer cell ... and found that RNASEH2A overexpression was associated with poor patient survival only in renal cell carcinomas (RCCs). Further ...
Genomic stability. Introduction. Mammalian cells generally require both mitogens and anchorage signals from a substratum to ... Incomplete cell-cycle arrest in suspended NSLT cells results in genomic instability. (A) Quantification of ,4N DNA content from ... Cells with oncogenic changes and genomic instability are reported to be more susceptible to mitotic death. To assess whether ... exhibited a strong cell-cycle arrest, with suspended cells mostly in the G1 phase of the cell cycle. By contrast, NSLT cells ...
Faithful chromosome segregation is essential for the maintenance of genetic stability during cell division. Eukaryotic cells ... Enhanced genomic instability and colonic tumorigenesis in BubR1+/-ApcMin/+ compound mutant mice. Chinthalapally V. Rao, Yang- ... Enhanced genomic instability and colonic tumorigenesis in BubR1+/-ApcMin/+ compound mutant mice ... Enhanced genomic instability and colonic tumorigenesis in BubR1+/-ApcMin/+ compound mutant mice ...
Maintaining genomic stability is one of the proposed functions for extensive genomic methylation in mammalian cells (18, 38). ... ANCs could be either an indication or cause of genomic instability. Genomic instability includes both chromosomal instability ( ... Previous work has demonstrated that DNA methylation can maintain genomic stability of cells (22). Cells lacking the Dnmt1 gene ... Increased Genomic Instability in MBD1-/- ANCs. Enhanced IAP expression has been found in cancer cells with chromosomal ...
Consequently, cell cycle checkpoints have evolved to monitor genomic stability and coordinate repair and cell cycle progression ... Defects in these processes cause genomic instability and predispose to cancer ( 2- 4). Key proteins involved in monitoring DNA ... Although in tumor cell lines ( 2, 17), embryonic stem cells ( 26- 28), and nonmammalian cells ( 29, 30), Chk1 has been reported ... After 6 h, cells were trypsinized, counted, and seeded in 60-mm dishes (1,000 cells per dish). After this, cells were kept ...
Seminar focusing on molecular pathways that maintain genomic stability in all cells and that carry out programmed changes in ... and instability; alteration in control of cell division and cell death; failure of differentiation; tumor angiogenesis and ... CONJ 536 Developmental Cell Biology (1.5) Wakimoto, Wright, Hille, Cooper [MCB]. Focuses on experimental design in cell biology ... Special attention devoted to understanding how failure in these pathways leads to genomic instability and malignancy. ...
The main research interests of the Lan Laboratory are centered on the mechanisms by which human cells maintain genomic ... main research interests of the Lan Laboratory are centered on the mechanisms by which human cells maintain genomic stability ... Telomere dysregulation is a major source of genomic instability and a potential target for cancer therapy. Due to G/C-rich ... main research interests of the Lan laboratory are centered on the mechanisms by which human cells maintain genomic stability ...
... main research interests of the Lan Laboratory are centered on the mechanisms by which human cells maintain genomic stability ... Telomere dysregulation is a major source of genomic instability and a potential target for cancer therapy. Due to G/C-rich ... main research interests of the Lan Laboratory are centered on the mechanisms by which human cells maintain genomic stability ... Oxidative DNA damage is a major source of genomic instability during tumorigenesis and aging. The ...
The Cimprich lab is focused on understanding how mammalian cells maintain genomic stability in the context of DNA replication ... Current Research and Scholarly Interests Genomic instability contributes to many diseases, but it also underlies many natural ... We are interested how the sensory epithelia of the inner ear that harbor the sensory hair cells develop, how the cells mature, ... Current Research and Scholarly Interests Genetic and cell biological analyses of signals controlling cell polarity and ...
The Cimprich lab is focused on understanding how mammalian cells maintain genomic stability in the context of DNA replication ... Current Research and Scholarly Interests Genomic instability contributes to many diseases, but it also underlies many natural ... Current Research and Scholarly Interests Genetic and cell biological analyses of signals controlling cell polarity and ... Current Research and Scholarly Interests My laboratory focuses on two main areas: 1) cancer stem cell biology and 2) novel ...
Because of this, chromosomal stability of the callus and/or somatic embryos should also be assessed. To this end, chromosome ... One of the main problems associated with tissue culture is the potential genetic instability of the regenerants. ... Here, we present an overview of the work done in conifers, with special emphasis on the production of a haploid cell line in ... Haploids are a valuable tool for genomic studies in higher plants, especially those with huge genome size and long juvenile ...
Genomic Instability/*genetics; Histone-Lysine N-Methyltransferase/*genetics; Protein Processing, Post-Translational/*physiology ... Cell Line, Tumor; Humans; Methylation; Histones/genetics/metabolism; Lysine/*metabolism; RNA, Small Interfering; Cell Cycle ... PR-Set7-dependent lysine methylation ensures genome replication and stability through S phase. Tardat, M.; Murr, R.; Herceg, Z ... PR-Set7/SET8 is a histone H4-lysine 20 methyltransferase required for normal cell proliferation. However, the exact functions ...
If these proteins are affected by somatic mutation or epigenetic silencing, eventual chromosomal instability and cell death can ... "The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability," Oncogene, vol. 25, no. 43, pp. ... L. K. Ashman, "The biology of stem cell factor and its receptor c-kit," The International Journal of Biochemistry & Cell ... Preclinical studies confirmed that BRCA-deficient cells were up to 1000-fold more sensitive than wild-type cells to PARP ...
RECQL5 Helicase and Genomic Stability[edit]. The enzyme RECQL5 helicase may also have a role in maintaining genomic stability. ... R-loops lead to genetic instability as the cell has trouble during replication trying to activate the S Phase checkpoints. ... fate of cells, stem cell pathways and differentiation, among other developmental matters. As proteins, they also contain ... When the cell wants to transcribe the DNA strand, the "TATA binding protein" (transcription factor) attaches to the TATA box ...
... downregulation of genes regulating genomic stability and cytokinesis in HRS cells may explain their genomic instability and ... GC B cells, (B) CD30+ EF B cells versus memory B cells, and (C) CD30+ EF B cells versus plasma cells (PC). (D) A comparison of ... GC B cells (42). (E) MYC expression in tonsillar CD30- cells (M, memory B cells; PC, plasma cells) and CD30+ GC and EF B cell ... B cells for the expression of CD27, a marker for memory B cells, GC B cells, and plasma cells (12, 13). Most cells of both CD30 ...
... downregulation of genes regulating genomic stability and cytokinesis in HRS cells may explain their genomic instability and ... CD30+ EF B cells represent active, proliferating memory B cells. HRS cells shared typical transcriptome patterns with CD30+ B ... and that CD30+ EF B cells are mostly post-GC B cells. The transcriptomes of CD30+ GC and EF B cells largely overlapped, sharing ... but were strikingly different from conventional GC B cells and memory B and plasma cells, respectively. CD30+ GC B cells ...
SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell 135, 907-918 (2008). ... Genomic Instability Group, Spanish National Cancer Research Center, 3 Melchor Fernandez Almagro Street, Madrid E-28029, Spain. ... 2f), and other investigators have found that Sirt1 contributes to maintain genomic stability5,6. On the basis of these ... In agreement with previous reports implicating Sirt1 in the maintenance of genomic stability5,6, we demonstrate here that Sirt1 ...
Our group investigates how breast cells lose control of proliferation and how this alters the DNA of cancer cells. ... A defining feature of breast cancer cells is uncontrolled proliferation and growth. ... Cyclin E2 induces genomic instability by mechanisms distinct from cyclin E1. Cell Cycle. 2013; 12(4):606-17. ... Cell cycle proteins in epithelial cell differentiation: Implications for breast cancer. Cell Cycle 2010; 9: 10. ...
We show that loss of SC35 in mouse embryonic fibroblasts induces G2/M cell cycle arrest and genomic instability, resulting at ... Splicing Regulator SC35 Is Essential for Genomic Stability and Cell Proliferation during Mammalian Organogenesis. Ran Xiao, Ye ... Inactivation of the SR protein splicing factor ASF/SF2 results in genomic instability. Cell 122:365-378. ... These findings reveal the involvement of SC35 in specific pathways in regulating cell proliferation and genomic stability ...
Together the entire telomere complex functions to maintain genome stability. However, each time a cell replicates and divides a ... stimulating the genomic instability that drives cancer progression. Therefore, the Laboratory of Genome instability and Cancer ... Laboratory of Genomic Instability and Cancer Therapeutics. Research. The telomere is a repetitive DNA element that protects the ... Telomere dysfunction is a major source of genomic instability contributing to the development of human cancer. The dynamics of ...
Cancer mechanogenomics, role of physical stresses on cancer genomic instability.. *Sanjay S Kumar M.S., Ph.D. Synaptic ... Role of histones in genome stability and cancer.. *Myra M Hurt Ph.D.. Molecular regulation of the cell division cycle. ... Research in this focus is typically conducted at the level of individual molecules and cells. Students working in this area can ...
This review summarizes recent findings of the function of BRCA1 and PTEN involved in genomic stability and cancer cell ... This review summarizes recent findings of the function of BRCA1 and PTEN involved in genomic stability and cancer cell ... Cells that lack PTEN have constitutively higher levels of PIP3 and activated downstream PI3K/AKT targets. BRCA1, a well-known ... Cells that lack PTEN have constitutively higher levels of PIP3 and activated downstream PI3K/AKT targets. BRCA1, a well-known ...
Scientific Experts about Experts and Doctors on genomic instability in Copenhagen, Capital Region, Denmark ... Mol Cell. 2014;53:1053-66 pubmed publisher ..Cells deficient for FoxM1 SUMOylation showed increased levels of polyploidy. Our ... A chaperone-assisted degradation pathway targets kinetochore proteins to ensure genome stability. PLoS Genet. 2014;10:e1004140 ... Experts and Doctors on genomic instability in Copenhagen, Capital Region, Denmark. Summary. Locale: Copenhagen, Capital Region ...
  • In conclusion, this study suggests that DNA damage and telomere dysfunction contribute to EBV-related chromosomal instability in early LCLs. (nih.gov)
  • Interestingly, this did not induce a stable arrest, but aberrant cell-cycle progression associated with stalled DNA replication, rereplication and chromosomal instability, which was sufficient to increase the frequency of oncogenic transformation. (biologists.org)
  • 2010. Loss of pRB causes centromere dysfunction and chromosomal instability. (wpi.edu)
  • 2006) and HCT116 cells, resulting in chromosomal instability (Iwaizumi et al. (atlasgeneticsoncology.org)
  • 2011). These results suggest that the short isoforms of SGOL1 function as a negative factor to native SGOL1, and that abundant expression of the SGOL1 short isoforms can be responsible for chromosomal instability. (atlasgeneticsoncology.org)
  • Chromosomal instability (CIN) is a characteristic feature of cancer. (mdpi.com)
  • Chromosomal instability of murine adipose tissue-derived mesenchymal stem cells in long-term culture and development of cloned embryos. (semanticscholar.org)
  • If partial loss of hRAP1 function causes chromosomal instability, as suggested by our current work, then mutations in RAP1 may be linked to a predisposition for cancer. (redorbit.com)
  • These results indicate that DNA hypomethylation plays a causal role in tumor formation, possibly by promoting chromosomal instability. (sciencemag.org)
  • Colorectal cancer arises from chromosomal instability, CpG island methylator phenotype and microsatellite instability [ 4 ]. (omicsonline.org)
  • Coexpression of Tax and PTTG enhanced chromosomal instability and neoplastic changes to levels greater than overexpression of either factor singularly. (asm.org)
  • Such an untimely activity by Tax could create chromosomal instability. (asm.org)
  • Because of our interest in understanding Tax, chromosomal instability, and cellular transformation ( 15 , 25 , 47 ), we wished to elucidate the interplay between PTTG and Tax in mammalian cells. (asm.org)
  • Therefore, the Laboratory of Genome instability and Cancer therapeutics is interested in understanding how normal telomeres are maintained, how dysfunctional telomeres arise, and how defects in this process contribute to the onset of cancer. (bu.edu)
  • 2014. Suppression of genome instability in pRB deficient cells by enhancement of chromosome cohesion. (wpi.edu)
  • So far, thorough investigations of the genetic basis of genome instability in CHO as well as effective mitigation strategies have been scarce. (keystonesymposia.org)
  • After culturing these DNA-repair-optimized cell lines over a period of 60 days, we analyzed chromosomal integrity by multi-color in-situ hybridization ("chromosome painting") and found that karyotypes showed fewer structural aberrations, compared to wildtype CHO, indicating successful mitigation of genome instability. (keystonesymposia.org)
  • Most human cancer cells show signs of genome instability, ranging from elevated mutation rates to gross chromosomal rearrangements and alterations in chromosome number. (semanticscholar.org)
  • In particular, we demonstrated that when cells encounter challenges to DNA synthesis, the organization of DNA replication drives the response to replication stress that is mediated by the ATR/Rad3 checkpoint pathway, thus shaping the pattern of genome instability along the chromosomes. (springer.com)
  • Aberrant topoisomerase-1 DNA lesions are pathogenic in neurodegenerative genome instability syndromes. (abcam.com)
  • Its ability to induce unlimited in vitro proliferation of B cells is frequently used to generate lymphoblastoid cell lines (LCLs). (nih.gov)
  • Indefinite proliferation of eukaryotic cells depends on telomerase that counteracts the depletion of DNA from chromosome termini due to the end replication problem. (nih.gov)
  • The combination of low CD151 expression and high RNASEH2A expression resulted in impaired proliferation in four kidney cancer cell lines, suggesting potential synthetic dosage lethality (SDL) interactions between the two genes. (mdpi.com)
  • Nucleotide metabolism homeostasis is important for the balance of cell proliferation, DNA replication, and genome stability [ 1 ]. (mdpi.com)
  • We report here that, although cyclin-CDK complexes persisted in suspension, proliferation was inhibited in LT-expressing cells by the CDK inhibitor p27 Kip1 (p27). (biologists.org)
  • Continued survival and proliferation following loss of contact with the extracellular matrix is dependent on the maintenance of intracellular signals in the absence of extracellular cues - a characteristic of transformed cells. (biologists.org)
  • This dependency of normal cells on specific anchorage signals for proliferation means that the checkpoints responsible for cell-cycle arrest in the absence of anchorage are likely to act as important tumour-suppressive mechanisms. (biologists.org)
  • Together, these mechanisms act to prevent cell-cycle progression in the absence of the appropriate anchorage signals and, as such, act as important regulatory mechanisms of cell-cycle control while also providing a safeguard against inappropriate proliferation. (biologists.org)
  • PR-Set7/SET8 is a histone H4-lysine 20 methyltransferase required for normal cell proliferation. (cnrs.fr)
  • A defining feature of breast cancer cells is uncontrolled proliferation and growth. (garvan.org.au)
  • Our group investigates how breast cells lose control of proliferation and how this alters the DNA of cancer cells. (garvan.org.au)
  • The helix-loop-helix protein Id1 requires cyclin D1 to promote the proliferation of mammary epithelial cell acini. (garvan.org.au)
  • Wilms' tumor protein 1: an early target of progestin regulation in T-47D breast cancer cells that modulates proliferation and differentiation. (garvan.org.au)
  • We report here that the SR protein SC35 controls cell proliferation during pituitary gland development but is completely dispensable in terminal differentiated mature cardiomyocytes in mice. (asm.org)
  • These findings reveal the involvement of SC35 in specific pathways in regulating cell proliferation and genomic stability during mammalian organogenesis and suggest its potential function in tumorigenesis. (asm.org)
  • Given the importance of pre-mRNA splicing in gene expression and in various developmental and disease processes ( 12 ), we are still at the beginning of understanding the roles of distinct splicing regulators in cell proliferation and cell cycle progression that lead to specific cellular and developmental phenotypes. (asm.org)
  • Here, on the basis of experiments using conditional mouse knockout and inducible somatic genetic complementation systems, we report that the SR protein SC35 plays a critical role in cell proliferation during pituitary development, but surprisingly it is dispensable in terminal differentiated mature cardiomyocytes in the heart. (asm.org)
  • The PI3K/AKT pathway might have an essential role in the proliferation of malignant tumor cells related to the BRCA1 functions (Figure 1 ). (frontiersin.org)
  • Phosphatase and tensin homolog on chromosome 10 (PTEN) is a dual protein/lipid phosphatase that inhibits the PI3K/AKT pathway, whose inhibition eventually reduces cell growth and cell proliferation ( 10 , 11 ). (frontiersin.org)
  • Examples of molecules known to act on DNA damage response, cell proliferation, and cell cycle via the regulatory pathways are shown. (frontiersin.org)
  • Neoplasia, or cancers, are defined as abnormal proliferation of genetically altered cells that can be caused by oncogenic viruses or predisposing conditions. (pubmedcentralcanada.ca)
  • Although some have postulated that the effect of estrogen on cell proliferation and apoptosis may be the reason ( 5 ), more specific underlying mechanism of why estrogen has anticolon cancer effect but has opposite effect on other cancers (for example endometrial cancer) remains to be investigated. (aacrjournals.org)
  • the end result of these defects is genomic instability, decreased cell proliferation, and premature cell senescence and death. (medscape.com)
  • MicroRNA16 regulates glioma cell proliferation, apoptosis and invasion by targeting Wip1-ATM-p53 feedback loop. (abcam.com)
  • Genomic imprinting results in the monoallelic expression of genes that encode important regulators of growth and proliferation. (biologists.org)
  • The controlled entry of cells into and through cell cycle stages is important to keep cellular proliferation in check. (fredhutch.org)
  • What is the array of strategies available to cancer cells as they achieve unlimited proliferation? (science-community.org)
  • During tumor development and in cancer therapy, HMGB1 has been reported to play paradoxical roles in promoting both cell survival and death by regulating multiple signaling pathways, including inflammation, immunity, genome stability, proliferation, metastasis, metabolism, apoptosis, and autophagy. (aacrjournals.org)
  • Targeted deletion of HuR in intestinal epithelial cells caused significant mucosal atrophy in the small intestine, as indicated by decreased cell proliferation within the crypts and subsequent shrinkages of crypts and villi. (jove.com)
  • For this purpose, we isolated adult retinal stem cells (RSCs) and studied their proliferation and differentiation potentials. (arvojournals.org)
  • His lab also discovered that Pot1b, the second Pot1 ortholog in the mouse genome, is required for stem cell proliferation. (yale.edu)
  • The Chang lab is also generating additional novel mouse models to understand mechanistically how dysfunctional telomeres activate apoptotic and/or cellular senescence pathways to suppress hematopoietic stem cell proliferation commonly observed in BM failure. (yale.edu)
  • In terms that increasingly recruit dynamics of increased cell proliferation there also evolves insensitivity to apoptosis of the tumor cells or of premalignant cells. (omicsonline.org)
  • It is with strict reference to increments of a coupling of increased tumor cell proliferation and anti-apoptosis that there emerge systems of genomic instability. (omicsonline.org)
  • Curcumin has promising potential in cancer prevention and therapy by interacting with proteins and modifying their expression and activity, which includes transcription factors, inflammatory cytokines and factors of cell survival, proliferation and angiogenesis. (portlandpress.com)
  • Taken together, this is the first paper to show that curcumin inhibits the transcriptional regulation of miR-21 via AP-1, suppresses cell proliferation, tumour growth, invasion and in vivo metastasis, and stabilizes the expression of the tumour suppressor Pdcd4 in colorectal cancer. (portlandpress.com)
  • Although checkpoint signaling is beneficial for preventing genomic instability, Rad53 signaling needs to be turned off following repair to allow for resumption of cell proliferation. (cornell.edu)
  • Similarly, in humans, activation of checkpoint kinases CHK1 and CHK2 must also be under stringent control to allow for cell proliferation. (cornell.edu)
  • Collectively, the results from my thesis reveal that checkpoint control is tightly regulated by multiple coordinated mechanisms to allow for cell proliferation following DNA damage. (cornell.edu)
  • S-phase checkpoints were investigated in Gadd45a(-/-) cells to determine possible defects contributing to the uncoupling of centrosome duplication and DNA replication. (nih.gov)
  • However, less is known about the possibility to selectively affect tumor cells when they are treated with agents that block DNA synthesis in combination with replication checkpoint inhibitors. (aacrjournals.org)
  • Here, we present clear insights in the different responses of tumor and non-transformed cells to the inhibition of DNA replication with hydroxyurea in combination with checkpoint abrogation via inhibition of Ataxia telangiectasia-mutated- (ATM) and Rad3-related/ATM (ATR/ATM) and Chk1 kinases. (aacrjournals.org)
  • Interestingly, we find that non-transformed cell lines activate ATR/ATM- and Chk1-independent pathways in response to replication inhibition to prevent mitotic entry with unreplicated DNA. (aacrjournals.org)
  • In contrast, tumor cell lines such as HCT116 and HeLa cells rely entirely on Chk1 activity for a proper response to replication inhibitors. (aacrjournals.org)
  • Furthermore, DNA replication arrest down-regulates cyclin B1 promoter activity in non-transformed cells, but not in tumor cells in a Chk1- and p38-independent way. (aacrjournals.org)
  • Thus, our data show that non-transformed cells present a more robust DNA replication checkpoint response compared with tumor cells that involves activation of the p38 pathway. (aacrjournals.org)
  • We show that some of these responses to replication block can be lost in tumor cells, causing a defective checkpoint and providing a rationale for tumor-selective effects of combined therapies. (aacrjournals.org)
  • To preserve genetic integrity, mammalian cells with stalled replication forks also activate a checkpoint response to delay the initiation of late origins (intra-S checkpoint) and mitotic entry (S/M checkpoint). (aacrjournals.org)
  • We have demonstrated one of the first known function for TERRA in that the cell cycle-regulated association of TERRA with telomeres drives a molecular switch coordinating telomere replication with telomere end protection. (bu.edu)
  • The Cimprich lab is focused on understanding how mammalian cells maintain genomic stability in the context of DNA replication stress and DNA damage. (stanford.edu)
  • Because cancer cells commonly feature intrinsically high replication stress, this study also provides a molecular rationale for their hypersensitivity to ATR inhibitors. (labome.org)
  • Collectively, these data indicate that PR-Set7-dependent lysine methylation during S phase is an essential posttranslational mechanism that ensures genome replication and stability. (cnrs.fr)
  • However, the stability of the genome is constantly threatened by DNA replication errors and by DNA damage due to a multitude of exogenous and endogenous factors, e.g., oxidative stress. (mdpi.com)
  • Genomic instability may result in numerous defects like replication errors, telomere dysfunction, epigenetic changes or defective DNA repair as a few examples. (mdpi.com)
  • 3) how the cell protects genome stability in response to DNA replication stress. (mdanderson.org)
  • Cycles of chromosome instability are associated with a fragile site and are increased by defects in DNA replication and checkpoint controls in yeast. (semanticscholar.org)
  • DSBs occur during normal DNA replication, in response to chemotherapeutic agents, and during physiological reactions including meiotic recombination in germ cells and antigen receptor rearrangements in lymphocytes. (cancer.gov)
  • Alterations to the replication profile are associated with cell fate changes during development and in pathologies, but the importance of undergoing S phase with distinct and specific programs remains largely unexplored. (springer.com)
  • Ahuja AK, Jodkowska K, Teloni F et al (2016) A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells. (springer.com)
  • Cornacchia D, Dileep V, Quivy J-P et al (2012) Mouse Rif1 is a key regulator of the replication-timing programme in mammalian cells. (springer.com)
  • Desprat R, Thierry-Mieg D, Lailler N et al (2009) Predictable dynamic program of timing of DNA replication in human cells. (springer.com)
  • Di Rienzi SC, Collingwood D, Raghuraman MK, Brewer BJ (2009) Fragile genomic sites are associated with origins of replication. (springer.com)
  • Donley N, Thayer MJ (2013) DNA replication timing, genome stability and cancer: late and/or delayed DNA replication timing is associated with increased genomic instability. (springer.com)
  • Feng W, Collingwood D, Boeck ME et al (2006) Genomic mapping of single-stranded DNA in hydroxyurea-challenged yeasts identifies origins of replication. (springer.com)
  • OriV (Origin of Replication): The sequence starting with which the plasmid-DNA will be replicated in the recipient cell. (wikipedia.org)
  • In mice, aging is accompanied by changes in expression of genes associated with increased inflammation, cellular stress, fibrosis, altered capacity for apoptosis, xenobiotic metabolism, normal cell-cycle control, and DNA replication [ 5 ]. (hindawi.com)
  • Viruses depend on host cells for replication, but how does a virus induce its host to transcribe its own genetic information alongside that of the virus, thus producing daughter viruses? (brightsurf.com)
  • Control (+/+) and Cdk2AF (AF/AF) cells were treated with hydroxyurea (HU) to perturb DNA replication. (fredhutch.org)
  • To analyze changes in the cellular recovery from replication stress, Cdk2AF/AF and control cells were briefly treated with hydroxyurea and cell cycle profiles were monitored after drug washout. (fredhutch.org)
  • As hydroxyurea treatment stalls DNA replication forks and increases the likelihood of DNA damage, the authors speculated that Cdk2AF/AF cells had acquired DNA damage during the drug treatment. (fredhutch.org)
  • These results confirmed that Cdk2 inhibitory phosphorylation protects cells from accumulating irreparable DNA damage and undergoing senescence during replication stress. (fredhutch.org)
  • They found that asynchronously growing Cdk2AF/AF cells had increased replication origin firing and decreased fork speed, a measure of elongation. (fredhutch.org)
  • The conflicts among the molecular mechanisms, such as replication, transcription, and translation are majorly responsible for the genomic instability, among which, transcription-replication conflict is well understood. (alliedacademies.org)
  • Formaldehyde, generated in cells or derived from the environment, can crosslink DNA to proteins, which interferes with DNA replication. (eurekalert.org)
  • DPCs inhibit this process by blocking the way of the unwinding enzyme replicative helicase, thus preventing replication and consequently cell division. (eurekalert.org)
  • Eukaryotic cells continuously experience DNA damage that can perturb key molecular processes like DNA replication. (biochemsoctrans.org)
  • Stabilization and protection of stalled replication forks ensures the possibility of effective fork restart and prevents genomic instability. (biochemsoctrans.org)
  • Recent efforts from multiple laboratories have highlighted several proteins involved in replication fork remodeling and DNA damage response pathways as key regulators of fork stability. (biochemsoctrans.org)
  • Ongoing work in this area continues to shed light on a sophisticated molecular pathway that balances the action of DNA resection and fork protection to maintain genomic integrity, with important implications for the fate of both normal and malignant cells following replication stress. (biochemsoctrans.org)
  • A reduced accuracy in DNA replication during tumor progression leads to marked heterogeneity of malignant cells and therapeutic resistance [ 2 ]. (omicsonline.org)
  • The genomes of cells are constantly challenged by DNA damage, DNA replication problems, and other forms of cellular stresses. (harvard.edu)
  • The checkpoint-mediated regulation and coordination of processes such as cell cycle transitions, DNA replication, DNA repair, transcription, and apoptosis are crucial for the stability of the genome. (harvard.edu)
  • We are also developing new assay systems to characterize stalled DNA replication forks in cells, and to visualize how replication and repair are coordinated. (harvard.edu)
  • We also show that exposure of wild-type yeast cells to the replication inhibitor hydroxyurea causes a Polζ-dependent increase in mutagenesis. (genetics.org)
  • Role of recombination and replication fork restart in repeat instability. (tufts.edu)
  • Oxidative DNA damage is a major source of genomic instability during tumorigenesis and aging. (massgeneral.org)
  • These cellular responses allow p53 to inhibit tumorigenesis and genomic instability. (asm.org)
  • BRCA1-related tumorigenesis may be mainly caused by increased DNA damage and decreased genome stability that is a major hallmark of cancer ( 3 ). (frontiersin.org)
  • Uncontrolled Cdk activity can increase the risk of tumorigenesis, and enhanced Cdk activity occurs in a range of tumor cells. (fredhutch.org)
  • Mutations that promote genomic instability, such as inactivation of DNA maintenance and/or repair factors, often occur early in the multistep process of tumorigenesis. (biologists.org)
  • Dr. Chang found that when WRN deficiency is coupled withtelomere dysfunction, the combination increases genomic instability, pre-matureaging and increased tumorigenesis. (yale.edu)
  • These important results suggest that dysfunctional telomeres could either suppress tumorigenesis by initiating cellular senescence (in the setting of an intact p53 pathway), or promote cancer through elevated genomic instability (in the setting of p53 deficiency). (yale.edu)
  • Mutations in polymerase delta in mice and humans promote genomic instability, mutator phenotype and tumorigenesis [ 1 ]. (omicsonline.org)
  • It is further to the dimensions of susceptibility ratios when contrasted with normal surrounding tissues that the tumorigenesis phenomenon both envelopes and further incorporates the varied heterogeneity of tumor cell sub-populations within a given neoplastic lesion. (omicsonline.org)
  • Thus the aberrant expression of imprinted genes may contribute to tumorigenesis or alter the differentiation potential of stem cells. (biomedcentral.com)
  • However, centrosome abnormalities occur frequently and often lead to monopolar or multipolar spindle formation, which results in chromosome instability and possibly tumorigenesis. (biologists.org)
  • Genomic instability facilitates tumor initiation and progression. (mdpi.com)
  • In the absence of anchorage signals from the extracellular matrix, many cell types arrest cell-cycle progression in G1 phase as a result of Rb-dependent checkpoints. (biologists.org)
  • Moreover, the ability of metastatic cells to colonise new microenvironments in vivo also relies on cell-cycle progression in the absence of normal extracellular stimuli. (biologists.org)
  • Together, our studies suggest that BubR1 and Apc functionally interact in regulating metaphase/anaphase transition, deregulation of which may play a key role in genomic instability and development and progression of colorectal cancer. (aacrjournals.org)
  • Consequently, cell cycle checkpoints have evolved to monitor genomic stability and coordinate repair and cell cycle progression ( 1 ). (aacrjournals.org)
  • These eroded telomeres are then recognized as substrates for DNA damage repair, stimulating the genomic instability that drives cancer progression. (bu.edu)
  • Although the causal relationship between dysregulated heterochromatin function and increased genomic instability is a well-recognized mechanism to promote cancer progression, this phenotype was largely inferred by biochemical analysis of chromatin-associated proteins and DNA sequences. (nature.com)
  • Uncovering SUMOylation dynamics during cell-cycle progression reveals FoxM1 as a key mitotic SUMO target protein. (labome.org)
  • Our findings contribute to understanding the role of SUMOylation during cell-cycle progression. (labome.org)
  • C ) Kinetics of cell cycle progression after γ irradiation. (sciencemag.org)
  • Although functional roles of BRCA1 may include the regulation of DNA damage repair, cell cycle progression, and maintenance of genomic integrity, the precise function of the BRCA1 gene as a tumor suppressor is still not clear. (frontiersin.org)
  • Telomerase reactivation in malignant cells after genomic instability causes cancer progression. (mdanderson.org)
  • As expected, the phenotypes were due to increased Cdk2 activity in Cdk2AF/AF cells since Cdk2 siRNA, or addition of a drug inhibitor of Cdk2 activity prior to hydroxyurea treatment, rescued cell cycle progression. (fredhutch.org)
  • In addition, through off-target activity, AID has a much broader effect on genomic instability by initiating oncogenic chromosomal translocations and mutations involved in the development and progression of lymphoma. (selleckchem.com)
  • Predilection for mutator phenotype dynamics has been invoked through the setting for selective genomic instability in a manner that underlies the whole integral progression of oncogenic mutation. (omicsonline.org)
  • In S. cerevisiae, the key DDC kinase Rad53 plays crucial roles in the regulation of transcription, dNTP levels, fork stability, cell cycle progression and origin firing. (cornell.edu)
  • The Hippo pathway downstream effector YAP regulates S-phase progression to protect neural stem cells of the retina from experiencing genomic instability. (elifesciences.org)
  • A number of studies have begun to dissect the role of mitotic kinases, including NIMA-related kinases (Neks), cyclin-dependent kinases (CDKs), Polo-like kinases (Plks) and Aurora kinases, in regulating centrosome duplication, separation and maturation and subsequent mitotic spindle assembly during cell cycle progression. (biologists.org)
  • Loss of p53 has been shown to lead to genomic instability in both normal and tumor cells ( 49 ). (asm.org)
  • The study concluded that chemical byproducts in electronic cigarette aerosol lead to genomic instability in oral epithelia, and chronic electronic cigarette exposure may increase mutagenic potential of oral epithelial cells. (ada.org)
  • Defects in these reactions lead to genomic instability, a confirmed driver of cancer and degenerative diseases. (science-community.org)
  • The failure of such controls leads to genomic instability and a predisposition to cancer ( 1 ). (sciencemag.org)
  • SPOP mutation leads to genomic instability in prostate cancer. (abcam.com)
  • BRCA1 and BRCA2 genes are responsible for 3-8% of all BCs and for 15-20% of familial cases ( 1 ), and because these genes are involved in maintaining genome integrity the complete loss of function of encoded proteins leads to genomic instability ( 2 , 3 ). (spandidos-publications.com)
  • However, despite inactivation of p53 and Rb proteins, SV40LT-expressing cells retain anchorage dependency, suggesting the presence of an uncharacterised cell-cycle checkpoint, which can be overridden by coexpression of oncogenic Ras. (biologists.org)
  • A chaperone-assisted degradation pathway targets kinetochore proteins to ensure genome stability. (labome.org)
  • Cell cycle proteins in epithelial cell differentiation: Implications for breast cancer. (garvan.org.au)
  • The overwhelming fraction of therapeutic proteins is expressed in Chinese Hamster Ovary (CHO) cells, due to their resistance to human viruses and their human-like glycosylation patterns. (keystonesymposia.org)
  • Viral nucleic acids and bacterial cell wall components (such as lipopolysaccharides or flagellar proteins) are PAMPs selectively detected by different types of innate immune receptors. (springer.com)
  • Western blotting was done using total proteins extracted from cultured cells and the antibodies for hMLH1 and hMSH2 (both from Proteintech Group, Inc.) and glyceraldehyde-3-phosphate dehydrogenase (Kangche BIO-TECH) according to the method described by Shiozawa et al. (aacrjournals.org)
  • In addition, a whole new concept in cell signaling bypassing the nuclear pores is provided by the recently discovered LINC complexes (Fig.1), which are built up by specific proteins in the inner and outer nuclear membranes. (su.se)
  • As a result of these discoveries it has now been realized that proteins of the NE orchestrate a much larger repertoire of functions than previously realized, both in cell signaling, chromatin organization and in the mitotic machinery. (su.se)
  • Signals from the cell surface may reach the nuclear interior via import of signaling proteins through the nuclear pores (Arabi et al. (su.se)
  • Notably, Wss1 has the unique property to cleave proteins only in the presence of DNA, suggesting that the enzyme is well tailored for its task to remove crosslinks from the genome and thus preserve genome stability. (eurekalert.org)
  • While single-particle tracking (SPT) in living cells with genetically encoded proteins is limited to very short trajectories, the high photon output of genetically targeted and multiplexed quantum dots (QDs) would enable long-trajectory analysis of multiple proteins. (jove.com)
  • This approach enables labeling and SPT of multiple genetically encoded proteins on living cells at high speed and can label expressed proteins in the cytosol upon microinjection into living cells. (jove.com)
  • Together these two proteins and the associated B cell receptor initiate intracellular signaling following antigen binding (4,5). (cellsignal.com)
  • Accurate repair of double stranded breaks is essential for cell survival and involves kinases, nucleases, helicases or core recombinational proteins [ 6 ]. (omicsonline.org)
  • To address these questions, we are developing new biochemical and cell biological assays to examine the functions of the key checkpoint proteins. (harvard.edu)
  • With a strong appreciation for how human health conditions, especially cancer and neurological maladies, are connected to the loss of genome integrity, ranging from intrinsic genetic predispositions to environmental factors that inflict DNA damage, my lab has developed the first single-cell assay to interrogate the molecular mechanisms of oxidative DNA damage response at specific loci in the genome. (massgeneral.org)
  • Here, we present an overview of the work done in conifers, with special emphasis on the production of a haploid cell line in maritime pine ( Pinus pinaster L.) and the use of a set of molecular markers, which includes Single Nucleotide Polymorphisms (SNPs) and microsatellites or Single Sequence Repeats (SSRs), to validate chromosomal integrity confirming the presence of all chromosomic arms. (mdpi.com)
  • Cabezas JA, Morcillo M, Vélez MD, Díaz L, Segura J, Cervera MT, Arrillaga I. Haploids in Conifer Species: Characterization and Chromosomal Integrity of a Maritime Pine Cell Line. (mdpi.com)
  • The maintenance of genomic integrity is essential for the health of multicellular organisms. (aacrjournals.org)
  • Some of those checkpoints are control pathways that delay or prevent cells from entering mitosis under conditions that can compromise genome integrity-for instance, in the presence of damaged or unreplicated DNA. (aacrjournals.org)
  • The maintenance of genomic integrity after DNA damage depends on the coordinated action of the DNA repair system and cell cycle checkpoint controls. (sciencemag.org)
  • Maintenance of genomic integrity is of the utmost importance for an organism's survival and a prerequisite for successfully passing on genetic information. (mdpi.com)
  • To maintain genomic integrity, cells are equipped with committed sensors to monitor DNA repair and/or to impose damaged cells into apoptotic cell death ( 4 ). (frontiersin.org)
  • We aim to understand how cells respond to DNA damage and safeguard the integrity of the genome. (mdanderson.org)
  • Evaluation of pH effects on genomic integrity in adipose-derived mesenchymal stem cells using the comet assay. (semanticscholar.org)
  • Emphasis will be placed on advances that provide mechanistic understanding of specific repair pathways that maintain genomic integrity to prevent disease. (keystonesymposia.org)
  • DNA methylation is an important epigenetic determinant in gene expression, maintenance of DNA integrity and stability, chromosomal modifications, and development of mutations. (aacrjournals.org)
  • Elsewhere in the University this work is complemented by the research groups of Dr Alastair Goldman, Professor Stuart Wilson, Dr Karen Sisley and Professor Carl Smythe, who each investigate how distinct normal and cancer cell types maintain genomic integrity and mRNA stability. (sheffield.ac.uk)
  • The genomic integrity of iPSCs after reprogramming must then be confirmed using chromosomal microarray and karyotype. (rochester.edu)
  • In humans, loss of genomic integrity is closely linked to cancers and other genetic diseases. (harvard.edu)
  • One important DNA repair mechanism to maintain genomic integrity is recombination. (tufts.edu)
  • Genomic stability is essential for normal cellular function, and highly conserved pathways have evolved to repair DNA damage and prevent genomic instability. (keystonesymposia.org)
  • These initial results by Hughes and colleagues suggest that Cdk2 inhibitory phosphorylation is required to prevent genomic instability in proliferating cells. (fredhutch.org)
  • To prevent genomic instability, DNA damage checkpoint (DDC) kinases are activated and coordinate various cellular responses. (cornell.edu)
  • One of the main problems associated with tissue culture is the potential genetic instability of the regenerants. (mdpi.com)
  • Earlier studies have shown an association between telomere shortening and advanced MDS and underlined the important role of dysfunctional telomeres in the development of genetic instability and cancer. (mdpi.com)
  • Clearly, genetic instability and clonal evolution are driving forces for leukemic transformation. (mdpi.com)
  • It has become clear, using rodent models as biological tools, that genetic instability in the form of gross DNA rearrangements or point mutations accumulate in the liver with age. (hindawi.com)
  • Indeed, the genetic instability in Cdk2AF/AF cells (as evidenced by micronuclei formation) was exacerbated by p21 knockdown. (fredhutch.org)
  • Driver oncogenic mutations presumably progress with expansion of clonally selected subpopulations of tumor cells in a manner that calls into operative modes the development of genetic instability. (omicsonline.org)
  • Genetic Instability is an enabling cancer phenotype associated with nearly all tumours. (sheffield.ac.uk)
  • For example, in mice, if there is a deficiency for SIRT6 (family member of Sir2), the mice experience genomic instability, metabolic defects, and degenerative pathologies in terms of aging, everything opposite of the roles of Sir2. (wikibooks.org)
  • Genomic instability in Gadd45a-/- cells is coupled with S-phase checkpoint defects. (nih.gov)
  • Defects in these processes cause genomic instability and predispose to cancer ( 2 - 4 ). (aacrjournals.org)
  • Whole chromosome instability (CIN) results from underlying defects in mitotic chromosome segregation and leads to gains and losses of entire whole chromosomes. (wpi.edu)
  • In the case of DT40 cells, cell mortality induced by ASF/SF2 depletion appears to be caused by multiple defects, including genomic instability triggered by elevated double-strand DNA break and subsequent apoptosis ( 26 , 27 , 29 ). (asm.org)
  • Since it has been shown that inappropriate activation of Cdk2 is monitored by a p53-dependent pathway, the researchers wondered whether p53 activation in Cdk2AF/AF cells was masking cell cycle defects in Cdk2AF/AF cells. (fredhutch.org)
  • Both pph3[DELTA] and slx4[DELTA] cells show selective sensitivity to methyl methanesulfonate (MMS), accumulate chromosomal defects and hyperactivate Rad53. (cornell.edu)
  • Moreover, BubR1 +/− Apc Min/+ MEFs slipped through mitosis in the presence of nocodazole and exhibited a higher rate of genomic instability than that of wild-type or BubR1 +/− or Apc Min/+ MEFs, which was accompanied by premature separation of sister chromatids. (aacrjournals.org)
  • Because Chk2 is thought to have a role in the prevention of entry into mitosis ( 2-4 ), we examined arrest of the cell cycle in ES cells, a cell type in which γ irradiation induces arrest in the G 2 phase but not arrest in the G 1 phase or apoptosis ( 7 ). (sciencemag.org)
  • We additionally investigated whether cells were able to enter M phase after γ irradiation by treatment with nocodazole, a microtubule-disrupting agent that traps cells in mitosis ( 8 , 9 ). (sciencemag.org)
  • In the absence of γ irradiation, about 35% of cells of both genotypes were trapped in mitosis after 12 hours of nocodazole treatment ( Fig. 1 D). When cells were subjected to γ irradiation with nocodazole treatment, cells of both genotypes arrested in G 2 for 12 hours ( Fig. 1 D). However, after 18 hours, significantly more Chk2 −/− cells entered mitosis. (sciencemag.org)
  • Loss of p53 sensitizes to antimicrotubule agents in human tumor cells, but little is known about its role during mitosis. (asm.org)
  • Since siRNA directed against Snk / Plk2 promoted death of paclitaxel-treated cells in mitosis, we envision a mitotic checkpoint wherein p53-dependent activation of Snk / Plk2 prevents mitotic catastrophe following spindle damage. (asm.org)
  • Previous studies had suggested that after treatment with spindle inhibitors, cells initially arrest in mitosis and then undergo adaptation and exit mitosis ( 51 ). (asm.org)
  • SGOL1 is a crucial factor to protect centromeric cohesin during mitosis and to maintain genomic stability in human cells. (atlasgeneticsoncology.org)
  • These protein complexes participate in many cellular functions, including vesicle transport and fusion, fragmentation and reassembly of the golgi stacks during mitosis, nuclear envelope formation and spindle disassembly following mitosis, cell cycle regulation, DNA damage repair, apoptosis, B- and T-cell activation, NF-κB-mediated transcriptional regulation, endoplasmic reticulum (ER)-associated degradation and protein degradation (4). (cellsignal.com)
  • They are gene-poor regions that present as chromatin dense heterochromatic structures in cells and are important for maintaining proper segregation of sister chromatids during mitosis ( 1, 2 ). (aacrjournals.org)
  • As part of the checkpoint response, Rad53 activation results in a major arrest in the cell cycle, which is thought to be important to increase the time in which DNA repair systems can function before the onset of mitosis, therefore preserving the faithful transmission of the genetic material to daughter cells. (cornell.edu)
  • As the cell enters mitosis and needs to partition replicated chromosomes into progeny nuclei, cleavage of cohesin by separase occurs. (asm.org)
  • When the cell undergoes mitosis, the duplicated centrosomes separate to define spindle poles and monitor the assembly of the bipolar mitotic spindle for accurate chromosome separation and the maintenance of genomic stability. (biologists.org)
  • BubR1 +/− Apc Min/+ MEF cells also proliferated at an accelerated rate and were more resistant to UV-induced cell death than wild-type MEFs or the cells with mutations in single genes. (aacrjournals.org)
  • However, in some cases mutations, like in oncogenes or tumor suppressor genes, may occur that allow the cell to bypass apoptosis and to survive. (mdpi.com)
  • How are the myriad helicases, nucleases and polymerases coordinated to safeguard genome stability, why are these molecules often mutated in human disease, and how can we ameliorate the effects of such mutations? (science-community.org)
  • Loss-of-function mutations in Notch receptors in cutaneous and lung squamous cell carcinoma. (labome.org)
  • Additionally, investigators have found that mutations in the CD79A (MB1) gene are associated with abnormally low levels of functional B cell receptors in some cases of chronic B cell lymphocytic leukemia (9). (cellsignal.com)
  • Ongoing genomic instability in cells such as CICs can subsequently allow for outgrowth of unique subclones, which acquire additional driver mutations that endow them with a selective growth advantage ( Hanahan and Weinberg, 2011 ). (biologists.org)
  • Theoretical uncertainties regarding the dimensions of mutator mutations are reflected particularly in the parameter uncertainties of the oncogenic pathways that are heterogeneous in individual tumor cells . (omicsonline.org)
  • Although initial or early mutator mutations may prove rare events in oncogenesis, the emergence also of passenger mutations reflect an essential establishment of a mutator phenotype as essential genomic instability and mutability. (omicsonline.org)
  • Cell fusion is a powerful inducer of aneuploidy , genomic instability and like mutations and aneuploidy might induce a mutator phenotype [ 7 ]. (omicsonline.org)
  • Initiator mutator mutations are regarded as rare events, and hence evolving genomic instability emerges as a generally later form of predisposition to ongoing oncogenesis. (omicsonline.org)
  • This project evaluates the degree of genomic instability (measured by combine CGH-SNP microarray) relative to the number of MDS-associated mutations (measured by next-generation sequencing) among cytopenic patients that underwent non-diagnostic bone marrow evaluation for MDS (i.e. patient's diagnosed with idiopathic cytopenias(s) of uncertain significance, or ICUS). (rochester.edu)
  • Future work will involve transforming human subject iPSCs into neuronal cell lines for the purposes of studying the effect of epilepsy causing mutations on neuronal morphology, development, and behavior. (rochester.edu)
  • Activation of these kinases results in the phosphorylation of a diverse array of downstream targets that participate in numerous cellular events, including DNA damage recognition and processing, cell cycle arrest, and apoptosis. (aacrjournals.org)
  • Telomeres that become critically short activate cell cycle checkpoints and promote the cellular senescence and/or apoptosis that drive organismal aging. (bu.edu)
  • Current Research and Scholarly Interests Our research is aimed at defining the pathways of p53-mediated apoptosis and tumor suppression, using a combination of biochemical, cell biological, and mouse genetic approaches. (stanford.edu)
  • Furthermore, we have demonstrated that the apoptosis due to silencing of Snk / Plk2 in the face of spindle damage occurs in mitotic cells and not in cells that have progressed to a G 1 -like state without dividing. (asm.org)
  • Cells which lack p53 do not arrest in G 1 phase after exposure to antimicrotubule agents and endoreduplicate their DNA, leading to massive apoptosis ( 7 , 9 , 22 , 32 ). (asm.org)
  • In this situation, the cell usually enters apoptosis. (mdpi.com)
  • Genomic instability finally induces cell death or apoptosis. (frontiersin.org)
  • The anti-proliferative activity of gemcitabine in pancreatic cancer results from p38 mitogen-activated protein kinase (MAPK) activation, which mediates cell apoptosis [ 9 ]. (omicsonline.org)
  • Niacin deficiency also impairs cell cycle arrest and apoptosis in response to DNA damage, which combine to encourage the survival of cells with leukemogenic potential. (aacrjournals.org)
  • The data from our rat model suggest that niacin supplementation of cancer patients may decrease the severity of short- and long-term side effects of chemotherapy, and could improve tumor cell killing through activation of poly(ADP-ribose)-dependent apoptosis pathways. (aacrjournals.org)
  • Work in my lab is focused on defining the cellular mechanisms that maintain genome stability in normal cells and understanding how these pathways are corrupted in cancer cells. (wpi.edu)
  • We analyzed whole-genome sequencing data from 11 CHO cell lines used in industrial protein production and found a high number of likely deleterious single-nucleotide polymorphisms (SNPs) in genes across all major DNA repair pathways. (keystonesymposia.org)
  • A genome-wide siRNA screen reveals diverse cellular processes and pathways that mediate genome stability. (semanticscholar.org)
  • Inhibiting telomerase, an enzyme that rescues malignant cells from destruction by extending the protective caps on the ends of chromosomes, kills tumor cells but also triggers resistance pathways that allow cancer to survive and spread, scientists report in the Feb. 17 issue of Cell. (mdanderson.org)
  • Publications] Yamashita,T.Wakao,H.Miyajima,A.& Asano S: 'Differentiation inducers modulate cytokine signaling pathways in a murine erythroleukemia cell line' Cancer Res.58. (nii.ac.jp)
  • For example, small molecule inhibitors of the repair enzyme PARP have shown significant potential for killing tumour cells that rely on specific DNA repair pathways, whilst leaving normal cells largely untouched. (sheffield.ac.uk)
  • The aim of the new Mainz-based CRC is to determine the factors that can cause genomic instability and its biological effects, the signaling pathways that are involved in detecting DNA damage and the mechanisms used by cells to protect themselves against this damage. (news-medical.net)
  • Tax influences host gene expression by interacting with and activating cellular signaling pathways, some of which can lead to dysregulated growth and malignant transformation of cells ( 2 , 12 , 14 , 36 , 37 , 44 , 65 ). (asm.org)
  • To achieve this goal, it is critical to elucidate the molecular pathways required to maintain the self-renewal, survival and genomic stability of hESCs. (ca.gov)
  • Because BRCA1 may play an essential role in maintaining genome stability, the mutation of BRCA1 is associated with increased genomic instability in cells ( 15 ), which consequently accelerates the mutation rate of other critical genes. (frontiersin.org)
  • Although MEK inhibition is essential for the naive state, here we show that reduced MEK inhibition facilitated the establishment and maintenance of naive hESCs that retained naive-cell-specific features, including global DNA hypomethylation, HERVK expression, and two active X chromosomes. (nature.com)
  • Eukaryotic cells have evolved a mechanism that delays the onset of anaphase until condensed chromosomes are properly positioned on the mitotic spindle. (aacrjournals.org)
  • Telomerase activity is low or absent in normal cells, which have segments of repeat nucleotides called telomeres at the ends of their chromosomes that protect DNA stability during cell division, said first author Jian Hu, Ph.D., an instructor in MD Anderson's Department of Cancer Biology. (mdanderson.org)
  • This conference will grapple with the intricate array of biochemical reactions orchestrated by the cell to replicate, repair and segregate chromosomes accurately despite constant threats from spontaneous and environmentally-induced damage. (science-community.org)
  • Dr. Chang's research program focuses on telomeres,repetitive DNA sequences at the ends of chromosomes critically important for the maintenance of genome stability. (yale.edu)
  • During a normal cell cycle, after chromosomes replicate in S phase, the duplicated chromosomes are "glued" together by a multisubunit cohesin complex ( 42 ). (asm.org)
  • Accordingly, aberration in the securin-separase-cohesin process can produce aneuploid daughter cells with gains and losses of whole chromosomes, a condition frequent in cancers ( 29 , 30 , 50 , 54 ). (asm.org)
  • Lu H, Huang YY, Mehrotra S, Droz-Rosario R, Liu J, Bhaumik M, White E, Shen Z. Essential roles of BCCIP in mouse embryonic development and structural stability of chromosomes. (cinj.org)
  • In addition, TERRA knockdown induces telomere dysfunction and instability. (bu.edu)
  • Cyclin E2 induces genomic instability by mechanisms distinct from cyclin E1. (garvan.org.au)
  • We show that loss of SC35 in mouse embryonic fibroblasts induces G 2 /M cell cycle arrest and genomic instability, resulting at least in part from p53 hyperphosphorylation and hyperacetylation. (asm.org)
  • p53 induces the expression of the p21 Cdk inhibitor to down-regulate Cdk activity, and the researchers found that p21 levels were increased in Cdk2AF/AF cells and inhibited Cdk2AF activity. (fredhutch.org)
  • Double knockout mice of H3K9 methyltransferases Suv39h1/2 exhibit chromosome instability and increased risk of tumor formation 7 . (nature.com)
  • 2014. Whole Chromosome instability resulting from the synergistic effects of pRB and p53 inactivation. (wpi.edu)
  • Sister chromatid exchange (SCE) frequency is widely used as an indicator of spontaneous chromosome instability. (spandidos-publications.com)
  • It's role within the cell is to link chromatin silencing to genomic stability, cellular metabolism, and lifespan regulation. (wikibooks.org)
  • Our findings indicate that DNA methylation is important in maintaining cellular genomic stability and is crucial for normal neural stem cell and brain functions. (pnas.org)
  • The relevance of this pathway in the response to DNA damage varies depending on the cell type, and it has been suggested that it may be an early response to cellular stress. (aacrjournals.org)
  • Our goal is to use molecular, genetic and cellular approaches to identify and characterize important players in the DNA damage response network that are required for maintaining genome stability and tumor suppression. (mdanderson.org)
  • We also apply this system to pluripotent cell culture and demonstrate that it faithfully indicates DNA methylation changes induced upon cellular reprogramming. (biologists.org)
  • Genome stability is the foundation upon which all cellular and organismal processes depend. (science-community.org)
  • Cutting-edge concepts in translational, genomic, cellular, molecular, RNA and structural biology will be dissected to take the conversation to unprecedented levels of depth and breadth. (science-community.org)
  • It is tempting to speculate that the higher genomic instability is related to cellular aging in adult RSCs. (arvojournals.org)
  • In response to such stresses, cells activate a complex signaling pathway, termed the checkpoint, to orchestrate various cellular responses. (harvard.edu)
  • The long-term goal of our research is to understand how checkpoint is activated by genomic instability and oncogenic stresses, and how it coordinates and integrates the network of cellular processes to preserve genomic stability. (harvard.edu)
  • Cellular immortalization is a major hallmark of cancer and is a multi-step process that requires numerous cell-type specific changes, including inactivation of control mechanisms and stabilization of telomere length. (diva-portal.org)
  • Escape from crisis was associated with downregulation of DNA damage response genes and altered expression of cell cycle regulators and genes controlling the cellular senescence program. (diva-portal.org)
  • Cancer cells are typically anchorage independent as a result of the disruption of these checkpoint mechanisms. (biologists.org)
  • The main research interests of the Lan laboratory are centered on the mechanisms by which human cells maintain genomic stability against oxidative stress. (massgeneral.org)
  • Cancer cells overcome the replicative senescence associated with critically short telomeres by exploiting mechanisms of telomere elongation. (bu.edu)
  • We have recently characterized several new ALT positive osteosarcoma and glioma stem cell lines and have begun to dissect the mechanisms required for ALT maintenance. (bu.edu)
  • Little is known about the molecular mechanisms that generate this instability or how it is suppressed in normal cells. (semanticscholar.org)
  • Dr. Nussenzweig is a leading contributor to the study of mechanisms that maintain genomic stability and prevent cancer. (cancer.gov)
  • The focus of the Recombination Unit is to understand the mechanisms by which all cell types monitor and repair DSBs. (cancer.gov)
  • However, the molecular mechanisms leading to the lesser effectiveness of gemcitabine in lung adenocarcinoma cells than in squamous carcinoma cells in terms of growth inhibition and cytotoxicity are poorly understood and remain to be elucidated. (omicsonline.org)
  • This meeting will focus on recent advances in understanding the nature and causes of genomic instability, the mechanisms of normal DNA repair, and the consequences of failure in DNA repair. (keystonesymposia.org)
  • This elegant model exposed two mechanisms, including one unexpected metabolic pathway, used by cancer cells to adapt to loss of telomerase. (mdanderson.org)
  • These findings allow us to anticipate how tumor cells might respond to telomerase inhibition and highlight the need to develop drug combinations that target telomerase and these adaptive resistance mechanisms," DePinho said. (mdanderson.org)
  • Constitutively active ErbB2 regulates cisplatin-induced cell death in breast cancer cells via pro- and antiapoptotic mechanisms. (abcam.com)
  • Fascinating and therapeutically crucial questions remain about the mechanisms underlying chromosome stability, and cross-disciplinary approaches are required to address them. (science-community.org)
  • To prevent this and also to cope with the huge amount of damage, cells can call on an array of repair mechanisms that protect our genes. (news-medical.net)
  • However, cells have a wide range of mechanisms that can protect and repair their DNA. (news-medical.net)
  • A cell's fate is largely determined by the interaction of these mechanisms that regulate the balance between cell death and cell survival, and also between error-free damage repair and development of a mutation. (news-medical.net)
  • In the broader context, mechanisms of this kind that are supposed to maintain genome stability actually also play a role in evolution, as they in effect increase the genetic diversity on which natural selection is based. (news-medical.net)
  • Experimental and computational models reveal how parallel 'core' mechanisms shape direction selectivity at the dendrites of starburst amacrine cells and ganglion cells in the mouse retina. (elifesciences.org)
  • This observation underlies the extraordinary tolerance of plant cells to telomere dysfunction. (nih.gov)
  • Current Research and Scholarly Interests Genomic instability contributes to many diseases, but it also underlies many natural processes. (stanford.edu)
  • Together, these studies show that radiation deregulates centrosome stability, which underlies genomic instability in normal human epithelial cells, and that this can be opposed by radiation-induced TGFbeta signaling. (labome.org)
  • Gene amplification in Gadd45a(-/-)p21(-/-) cells correlated with loss of both G(1) and S-phase checkpoints. (nih.gov)
  • This is of particular importance for solid tumors, which may lack sufficient nutrients yet are unable to elicit checkpoints preventing genomic instability under these conditions. (nih.gov)
  • Actually, studies have established functional roles for BRCA1 in DNA damage signaling, DNA repair processes, and cell cycle checkpoints ( 16 , 17 ). (frontiersin.org)
  • One major current effort is to study the interplay between NHEJ, HR and cell cycle checkpoints in maintaining genomic stability. (cancer.gov)
  • Telomere dysfunction is a major source of genomic instability contributing to the development of human cancer. (bu.edu)
  • Perturbation of telomere length results in telomere dysfunction, leading to increased genomic instability that can promote early aging and cancer development. (yale.edu)
  • Why is catalytic activity required for chromatin association in the cell? (wikibooks.org)
  • What is the characteristic molecular-scale chromatin abnormality in cancer cells? (nature.com)
  • Aberrant chromatin structure is a characteristic of cancer cells, but what happens in early carcinogenesis when cells still appear normal prior to tumor formation? (nature.com)
  • 3) determine the influence of chromatin structure on the maintenance of genomic stability. (cancer.gov)
  • In both cancer and ICF, the instability of pericentromeric regions is associated with DNA demethylation and chromatin decondensation ( 9-11 ). (aacrjournals.org)
  • It plays a key role in maintaining genomic stability. (aacrjournals.org)
  • Human MutS homolog 2 (MSH2) is a key DNA mismatch repair protein that plays an important role in maintaining genomic stability. (omicsonline.org)
  • To further understand the molecular basis of this surveillance mechanism in human cells, we have been studying the role of a spindle checkpoint kinase BubR1 and Adenomatous Polyposis Coli ( Apc ) in the regulation of genomic stability and tumor suppression. (aacrjournals.org)
  • Although the molecular mechanism of MMR in the eukaryotic cell is still not completely understood, increased used of single-molecule analyses in the future may yield new insight into these unsolved questions. (labome.org)
  • Finally, various molecular adaptations of plasmids to better match the genetic background of their bacterial host cell will be described. (labome.org)
  • Using a combination of molecular and cell biological approaches, together with bioinformatics and imaging techniques, my group aims to identify changes associated with genomic instability in cancer and exploit these changes to identify novel therapeutic targets and enhance cancer cell death. (wpi.edu)
  • Institute of Cell and Molecular Pathology, Hannover Medical School, Carl-Neuberg-Str. (mdpi.com)
  • Molecular regulation of the cell division cycle. (fsu.edu)
  • Outside of the cell, HMGB1 is a prototypical damage-associated molecular pattern, acting with cytokines, chemokines, and growth factors. (aacrjournals.org)
  • This interdisciplinary alliance will bring together experts in structural biology, organic chemistry, biochemistry, cell and molecular biology as well as genetic toxicology. (news-medical.net)
  • In cancer cells, the genes governing checkpoint activation are often and as a result, critically short telomeres fail to induce cell cycle arrest. (bu.edu)
  • A remarkable downregulation of genes regulating genomic stability and cytokinesis in HRS cells may explain their genomic instability and multinuclearity. (jci.org)
  • Martins C, Kedda M, Kew M. Characterization of six tumor suppressor genes and microsatellite instability in hepatocellular carcinoma in southern African blacks. (wjgnet.com)
  • These results show for the first time that correction of only few DNA repair genes can results in considerable improvements in DNA repair, genome stability, and protein expression in CHO. (keystonesymposia.org)
  • The 17 genes associated with genomic instability strongly impacted clinical outcome in breast cancer. (gu.se)
  • In this study, we investigated the effect of estrogen on the expression of two representative MMR genes ( hMLH1 and hMSH2 ) in cultured malignant colonic epithelial cells, and correlated the serum estrogen level with MMR gene expression in human colonic epithelial cells from 42 healthy individuals. (aacrjournals.org)
  • The examined genes had tendency to be down-regulated in MCF-7 cells treated with EMF. (cancerindex.org)
  • Activation-induced cytidine deaminase (AID) is a B-cell-specific enzyme that targets immunoglobulin genes to initiate class switch recombination and somatic hypermutation. (selleckchem.com)
  • PRDM14 functions in embryonic stem cell (ESC) maintenance to promote the expression of pluripotency-associated genes while suppressing differentiation genes. (biologists.org)
  • PCGF6 links sequence specific target recognition by the MAX/MGA transcription factor complex to PRC1 (polycomb repressive complex 1) -dependent transcriptional silencing of germ cell-specific genes in mouse pluripotent stem cells. (elifesciences.org)
  • However, consistent with the complexity and redundancy of the anchorage-checkpoint process, several oncogenic changes are required to confer anchorage independence on normal cells. (biologists.org)
  • As such, stem and progenitor cells are the likely targets for oncogenic insults that lead to transformation and subsequent conversion to CICs. (biologists.org)
  • Furthermore, checkpoint is activated at the early stage of human tumorigensis, suggesting a role of checkpoint as an anti-cancer barrier against the genomic instability induced by oncogenic stresses. (harvard.edu)
  • Human embryonic stem cells (hESCs) can be captured in a primed state in which they resemble the postimplantation epiblast, or in a naive state where they resemble the preimplantation epiblast. (nature.com)
  • Human embryonic stem cells do not change their X inactivation status during differentiation. (nature.com)
  • Self-renewal and scalability of human embryonic stem cells for human therapy. (ca.gov)
  • Human embryonic stem cells (hESCs) can undergo unlimited self-renewal and retain the pluripotency to differentiate into all cell types in the body. (ca.gov)
  • 2015). We revealed the unique epigenetic strategies in human embryonic stem cells (hESCs) that control p53 target gene expression for maintaining homeostasis and genomic stability in ESCs (Itahana Y et al. (duke-nus.edu.sg)
  • Histone modifications and p53 binding poise the p21 promoter for activation in human embryonic stem cells. (duke-nus.edu.sg)
  • The telomeres at the chromosome ends are essential for genomic stability, and limit the growth potential of most cells. (diva-portal.org)
  • By limiting the number of plasmids in the cells the potential for recombination is decreased, thus preserving the genome insert. (wikipedia.org)
  • It has been found that the stability increases dramatically when the human DNA inserts are present in single copies in recombination deficient E. coli cells. (wikipedia.org)
  • Cells can repair such DSBs by homologous recombination (HR) or nonhomologous end-joining (NHEJ). (genetics.org)
  • Though early studies dismissed recombination as a mechanism driving repeat expansion and instability, recent results indicate that mitotic recombination is a key pathway operating within repetitive DNA. (tufts.edu)
  • In this review, we summarize recent developments that illuminate the role of recombination in maintaining genome stability at DNA repeats. (tufts.edu)
  • Genomic instability is a hallmark of cancer. (nih.gov)
  • Genomic instability is a hallmark of cancer that plays a pivotal role in breast cancer development and evolution. (gu.se)
  • Whereas yeast and mammalian cells lacking telomerase appear to readily adopt alternative telomere lengthening (ALT), in Arabidopsis ALT is inhibited by the Ku heterodimer. (nih.gov)
  • Mammalian cells generally require both mitogens and anchorage signals in order to proliferate. (biologists.org)
  • Mammalian cells generally require both mitogens and anchorage signals from a substratum to proliferate ( Assoian and Schwartz, 2001 ). (biologists.org)
  • Derivation of ground-state female ES cells maintaining gamete-derived DNA methylation. (nature.com)
  • Previous work has demonstrated that DNA methylation can maintain genomic stability of cells ( 22 ). (pnas.org)
  • In addition, the pattern of site- and gene-specific DNA methylation induced by folate deficiency may not be in concert with the direction of changes in genomic DNA methylation. (aacrjournals.org)
  • Human cancer cells often display abnormal patterns of DNA methylation. (sciencemag.org)
  • To investigate whether DNA hypomethylation has a causal role in tumor formation, we generated mice with highly reduced levels of Dnmt1, the enzyme that maintains DNA methylation patterns in somatic cells ( 6 ). (sciencemag.org)
  • Genomic DNA was digested with the methylation-sensitive restriction enzyme Hpa II and probed with an IAP cDNA probe ( 10 ). (sciencemag.org)
  • Gadd45a is a p53-regulated gene whose protein product, like p53, is involved in maintenance of genome stability. (nih.gov)
  • Gadd45a deletion allows another form of genomic instability, gene amplification, when p21 (Cdkn1a gene product) is deleted also. (nih.gov)
  • We screened the nucleotide degrading enzyme gene expression in RNAseq data of 14 cancer types derived from The Cancer Genome Atlas (TCGA) and found that RNASEH2A overexpression was associated with poor patient survival only in renal cell carcinomas (RCCs). (mdpi.com)
  • Cells lacking the Dnmt1 gene have 50-100 times higher levels of intracisternal A particle (IAP), a type of endogenous virus whose expression levels are frequently elevated in cancer cells with genomic instability ( 22 ). (pnas.org)
  • We generated Chk2-deficient mouse cells by gene targeting. (sciencemag.org)
  • To investigate the physiological role of Chk2, we generated Chk2-deficient cells by gene targeting in embryonic stem (ES) cells ( 5 ). (sciencemag.org)
  • Phenotypic and IgV gene analyses indicated that CD30+ GC B lymphocytes represent typical GC B cells, and that CD30+ EF B cells are mostly post-GC B cells. (jci.org)
  • The p53 target gene p21 WAF1 has been implicated in mediating this G 1 arrest, as p21 knockout mouse embryonic fibroblasts or p21 somatic knockout cells undergo a similar endoreduplication after treatment with spindle inhibitors ( 20 , 22 , 41 ). (asm.org)
  • They are implicated in different aspects of gene expression processes, including transcription, RNA stability, mRNA transport, and translational control. (asm.org)
  • Matched gene expression profiles showed an innate segregation based on genome stability. (gu.se)
  • However, there has been no direct examination of the effects of estrogen on MMR gene expression in colonic epithelial cells. (aacrjournals.org)
  • Human MutS homolog 2 (MSH2), a crucial element in the DNA mismatch repair (MMR) system, maintains genetic stability and avoids gene mutation in cells [ 11 ]. (omicsonline.org)
  • ALT-positive cells increase both the expression and copy number of a gene called PGC-1ß, a key regulator of mitochondrial function, to compensate for mitochondrial and reactive oxygen species defense deficiencies. (mdanderson.org)
  • Spontaneous ATM Gene Reversion in A-T iPSC to Produce an Isogenic Cell Line. (abcam.com)
  • generated a human cell line in which the Cdk2 gene was replaced with the Cdk2AF allele, to produce an abnormally active protein that could not be phosphorylated at T14 or Y15. (fredhutch.org)
  • The DNA glycosylase gene MBD4 safeguards genomic stability at CpG sites and may contribute to carcinogenesis by acting as modifier of MMR-deficient cancer phenotype [ 8 ]. (omicsonline.org)
  • In Rko and HCT116 cells, we identified two new transcriptional start sites of the miR-21 gene and delineated its promoter region. (portlandpress.com)
  • Genomic imprinting is an epigenetic phenomenon through which monoallelic gene expression is regulated in a parent-of-origin-specific manner. (biomedcentral.com)
  • Together the entire telomere complex functions to maintain genome stability. (bu.edu)
  • Histone H2AX Is Involved in FoxO3a-Mediated Transcriptional Responses to Ionizing Radiation to Maintain Genome Stability. (abcam.com)
  • Given the heterogeneity of cancer cells in tumors, it is critical to understand how dividing and non-dividing cells respond to oxidative DNA damage. (massgeneral.org)
  • The second is a series of spontaneous thymic lymphoid tumors that occurred in the African frog Xenopus laevis ( 14 ) from which stable tumor lymphoid cell lines were derived. (pubmedcentralcanada.ca)
  • Cells that overexpressed both PTTG and Tax induced tumors more robustly in nude mice than cells that expressed either PTTG alone or Tax alone. (asm.org)
  • Interestingly, applying these findings to tumors of T cell origin revealed commonly methylated CpG sites in transformed cells. (diva-portal.org)
  • Prolonged Mek1/2 suppression impairs the developmental potential of embryonic stem cells. (nature.com)
  • Chk2 −/− embryonic stem cells failed to maintain γ-irradiation-induced arrest in the G 2 phase of the cell cycle. (sciencemag.org)
  • Mice are the most commonly used laboratory animals for research, and some mouse stem cells, such as induced pluripotent stem cells, embryonic stem cells, and mesenchymal stem cells (MSCs), are also widely used in basic research. (semanticscholar.org)
  • Dnmt1 chip/- embryonic stem (ES) cells expressed 10% of wild-type levels ( Fig. 1A ). (sciencemag.org)
  • Southern blot analysis of embryonic fibroblasts and adult tissues showed that the DNA from compound heterozygotes was hypomethylated relative to the DNA from Dnmt1 chip/chip or Dnmt1 +/+ mice, although substantially less so than the DNA from Dnmt1 -/- null ES cells. (sciencemag.org)
  • HeLa, HCT116, murine embryonic fibroblast, and NIH 3T3 cells were maintained in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal calf serum (FCS). (asm.org)
  • A novel lncRNA (Ephemeron) is connected to known post-transcriptional and epigenetic regulators as part of an integrated machinery, which controls the timely exit from the naïve state of mouse embryonic stem cells. (elifesciences.org)
  • Polycomb enables lineage priming in mouse embryonic stem cells by establishing a barrier to commitment. (elifesciences.org)
  • Our results show that p38 is activated in response to hydroxyurea treatment and collaborates with Chk1 to prevent mitotic entry in non-transformed cell lines by maintaining cyclin B1/Cdk1 complexes inactive. (aacrjournals.org)
  • Because Cdc25 phosphatase family activates cyclin B1/Cdk1, which is essential for mitotic entry, the cell cycle is finally arrested at the G 2 -M transition. (aacrjournals.org)
  • Although p53 plays an important function in maintaining genomic stability, little is known about a role in enforcing the mitotic spindle checkpoint. (asm.org)
  • SGOL1-knockdown caused severe mitotic arrest and precocious separation of centromeric cohesion in HeLa cells (Salic et al. (atlasgeneticsoncology.org)
  • The centrosome acts as the major microtubule-organizing center (MTOC) for cytoskeleton maintenance in interphase and mitotic spindle assembly in vertebrate cells. (biologists.org)
  • In this Commentary, we review the recent research progress on how these mitotic kinases are coordinated to couple the centrosome cycle with the cell cycle, thus ensuring bipolar mitotic spindle fidelity. (biologists.org)
  • Dr. Jeffrey Kim, Ph.D., presented "Standardized Electronic-Cigarette Aerosol Alters Genomic Stability of Oral Epithelial Cells. (ada.org)
  • Researchers standardized electronic cigarette testing parameters and identified potential hazardous byproducts in electronic cigarette aerosol that contribute to genomic instability in oral epithelial cells. (ada.org)
  • Most of our knowledge of the immortalization process is based on analyses of human fibroblast and epithelial cell cultures immortalized by genetic modification. (diva-portal.org)
  • However, we found that MBD1 -/- neural stem cells exhibited reduced neuronal differentiation and increased genomic instability. (pnas.org)
  • Isolation, Culture, Differentiation, and Nuclear Reprogramming of Mongolian Sheep Fetal Bone Marrow-Derived Mesenchymal Stem Cells. (semanticscholar.org)
  • Leukemia is preceded by a dramatic expansion of cells resembling hematopoietic stem cells and lymphoid-committed progenitors prior to disease onset, accompanied by a blockage in B-cell differentiation at the early pro-B stage. (biologists.org)
  • Reprogramming relies on the successful erasure of marks of differentiation while maintaining those required for genomic imprinting. (biomedcentral.com)
  • Analysis of genomic imprints in hiPSCs is a necessary safety step in regenerative medicine, with relevance both to the differentiation potential of these stem cells and also their potential tumorigenic properties. (biomedcentral.com)
  • The possibility to study allele-specific expression in different contexts makes our reporter system a useful tool to dissect the regulation of genomic imprinting in normal development and disease. (biologists.org)
  • In summary, we show that PI3Kδ or Bruton's tyrosine kinase inhibitors increase genomic instability in normal and neoplastic B cells by an AID-dependent mechanism. (selleckchem.com)
  • Comprehensive cell surface protein profiling identifies specific markers of human naive and primed pluripotent states. (nature.com)
  • The telomere capping protein TRF2 was partially displaced from telomeres in EBV-infected cells, suggesting an EBV-mediated uncapping problem. (nih.gov)
  • this asymmetry can age the mother cell by forming toxic protein aggregates. (wikibooks.org)
  • Chk2 is a protein kinase that is activated in response to DNA damage and may regulate cell cycle arrest. (sciencemag.org)
  • Chk2 is a protein kinase that acts downstream of ataxia teleangiecstasia mutated (ATM) and may regulate cell cycle arrest ( 2-4 ). (sciencemag.org)
  • The genotype of Chk2 −/− ES clones was confirmed by Southern (DNA) blotting ( Fig. 1 A), and complete loss of Chk2 protein in Chk2 −/− cells was confirmed by protein immunoblotting ( Fig. 1 B) ( 6 ). (sciencemag.org)
  • B ) Protein immunoblot showing the expression of mouse Chk2 in ES cells either left untreated or subjected to γ irradiation (IR) (10 Gy, 3 hours). (sciencemag.org)
  • When the cell wants to transcribe the DNA strand, the "TATA binding protein" (transcription factor) attaches to the TATA box and subsequently helps in getting the RNA polymerase to attach there and begin synthesizing the RNA. (wikibooks.org)
  • Similarly, in experiments using chicken DT40 cells or mouse embryo fibroblasts (MEFs) derived from conditional knockout embryos, ablation of SR protein ASF/SF2 gave rise to a cell-lethal phenotype ( 32 , 47 ). (asm.org)
  • However, efficient high-yield protein expression remains aggravated by the instability of the CHO genome, as random chromosome rearrangements and deletions can reduce transgene copy number and lead to a loss in protein titer. (keystonesymposia.org)
  • Enforced expression of constitutively active MKK6 rescued cell viability and restored MSH2 protein levels that were suppressed by curcumin and gemcitabine. (omicsonline.org)
  • The bornavirus-derived human protein EBLN1 promotes efficient cell cycle transit, microtubule organisation and genome stability. (abcam.com)
  • All four FA-D cell lines remained sensitive to Mitomycin C, despite FAA phosphorylation, FAA/FAC binding, and normal nuclear accumulation of the protein complex. (nii.ac.jp)
  • Inside the cell, HMGB1 is a highly conserved chromosomal protein acting as a DNA chaperone. (aacrjournals.org)
  • In the laboratory of Stefan Jentsch at the Max-Planck-Institute of Biochemistry, scientists now identified the protease Wss1 as a new safeguarding factor that chops down the protein components of DNA-protein crosslinks and thereby enables cells to duplicate their genome. (eurekalert.org)
  • Julian Stingele, a PhD student in the laboratory, found that cells lacking Wss1 are particularly sensitive to formaldehyde, extremely vulnerable to DNA-protein crosslinks and suffer from genomic instability. (eurekalert.org)
  • The newly identified DNA-protein crosslink-repair pathway is particularly important for rapidly dividing cells. (eurekalert.org)
  • The RNA-binding protein HuR is highly expressed in the gut mucosa and modulates the stability and translation of target mRNAs, but its exact biological function in the intestinal epithelium remains unclear. (jove.com)
  • Hafezi Y, Bosch J, Hariharan I. Differences in levels of the transmembrane protein Crumbs can influence cell survival at clonal boundaries. (labome.org)
  • RT-PCR analysis shows that these cells expressed several markers characteristic of stem cells (c-kit, Bmi1, Sox2) and Mash1, a bHLH pro-neural protein. (arvojournals.org)
  • A ) Immunoblot analysis of protein extracts from ES cells, using a C-terminal Dnmt1 chicken antibody ( 34 ). (sciencemag.org)
  • A number of studies have shown that the C-terminal sequence is critical for maintaining PTEN protein stability ( 7 ). (aacrjournals.org)
  • Dr. Chang's laboratory recently discovered that the POT1 (Protection of Telomere 1) protein is an integral member of a protein complex that binds to telomeres and is essential for the maintenance of telomere stability. (yale.edu)
  • Curcumin treatment reduced miR-21 promoter activity and expression in a dose-dependent manner by inhibiting AP-1 binding to the promoter, and induced the expression of the tumour suppressor Pdcd4 (programmed cell death protein 4), which is a target of miR-21. (portlandpress.com)
  • Marian Blanca Ramírez from the CSIC in Spain has been studying the effects of LRRK2, a protein associated with Parkinson's disease, on cell motility. (biologists.org)
  • Going forward, we would like to expand our studies to investigate the status of this new RNA-mediated HR repair pathway in cancer cells, its potential function in tumor suppression, and its value as a therapeutic target. (massgeneral.org)
  • This research contributes to our understanding of chromosome stability and, thereby, tumor suppression and cancer. (redorbit.com)
  • The nuclear envelope acts as a signaling node to provide enhanced diversification in cell surface to nucleus signaling in eukaryotic cells, a phenomenon which may be especially important in the highly polarized and elongated neuronal cell. (su.se)
  • The LINC complexes also play important roles in migration of nuclei taking place, e.g. when neuronal cells divide in the developing mammalian brain as well as in muscles for specific positioning of nuclei at neuromuscular junctions. (su.se)
  • 1999). The extended tubular shape of neurites addresses particular questions regarding diffusion-mediated signaling in neuronal cells, which may to a large extent rely on motor driven propagation of signals between the cell surface and the nucleus. (su.se)
  • To study the impact of reactivated telomerase, DePinho and colleagues genetically modified mice to develop T cell lymphomas and to have telomerase reactivated when the mice are treated with 4-hydroxytamoxifen (4-OHT). (mdanderson.org)
  • The mutant mice were runted at birth, and at 4 to 8 months of age they developed aggressive T cell lymphomas that displayed a high frequency of chromosome 15 trisomy. (sciencemag.org)
  • Genomic hypomethylation in Dnmt1 hypomorphic mice. (sciencemag.org)
  • When R26PR is mated to either of two Cre lines, Mx1-cre or MMTV-cre, mice develop early-onset T-cell acute lymphoblastic leukemia (T-ALL) with median overall survival of 41 and 64 days for R26PR;Mx1-cre and R26PR;MMTV-cre, respectively. (biologists.org)
  • The ability of CIN cancer cells to 'shuffle' their genomic content can lead to gains of oncogenes, loss of tumor suppressors, and promotes tumor cell evolution. (wpi.edu)
  • Bester AC, Roniger M, Oren YS et al (2011) Nucleotide deficiency promotes genomic instability in early stages of cancer development. (springer.com)
  • In p53 null cells, this elevated genomic instability promotes malignant transformation and rapid onset of cancer. (yale.edu)
  • Ca2+-dependent PP2Ac demethylation promotes cancer cell death in response to glucose deprivation independently of inhibiting glycolysis. (duke-nus.edu.sg)
  • Mutation of the de novo DNA methyltransferase 1-36 (Dnmt3b) causes immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome in humans, with characteristics of genomic instability ( 18 ). (pnas.org)
  • We demonstrated a novel role of ARF in preventing genomic instability caused by centrosome amplification (Neo S et al. (duke-nus.edu.sg)
  • We thus provide a simple modification to current methods that can enable robust growth and reduced genomic instability in naive hESCs. (nature.com)
  • Therefore, as a renewable source of various cell types, hESCs hold great promise for human cell replacement therapy. (ca.gov)
  • One such challenge is to develop strategies to scale-up the production of clinic-grade hESCs in xeno-free and chemically defined medium without inducing genomic instability. (ca.gov)
  • ALT activation increases karyotype stability in the majority of tert ku70 cell lines, which contrasts with ongoing chromosomal rearrangements detected in survival tert cultures that lack any detectable telomeric sequences. (nih.gov)
  • Dramatic increases in the level of genomic instability can occur during normal cell development and aging, and genomic instability is also associated with genetic disease and cancer. (keystonesymposia.org)
  • Recently it was reported that Tax directly binds the Cdc20-associated anaphase-promoting complex to induce premature degradation of PPTG/securin and Clb2p/cyclin B1 in yeast and human cells ( 32 , 33 ). (asm.org)
  • Taken together, the findings point to a central role of CSL in telomere homeostasis with important implications for genomic instability of cancer stromal cells and beyond. (nih.gov)
  • Comparison of clinical grade human platelet lysates for cultivation of mesenchymal stromal cells from bone marrow and adipose tissue. (labome.org)
  • Low dose radiation induced senescence of human mesenchymal stromal cells and impaired the autophagy process. (abcam.com)
  • If such a cell acquires additional genetic alterations providing a clonal advantage, this may lead to malignant transformation and ultimately to cancer [ 1 ]. (mdpi.com)
  • The key attribute of marked heterogeneity in genomic lesions attests for the essential evolution of the mutator phenotype per se, and allows for the emergence of oncogenesis beyond initial or middle course events in malignant transformation. (omicsonline.org)
  • Collectively, currently available evidence indicates that genomic DNA hypomethylation in the colorectum is not a probable mechanism by which folate deficiency enhances colorectal carcinogenesis. (aacrjournals.org)
  • On average, the genetic information of every cell in our body is damaged approximately 10,000 times a day, and each of these injuries can, in principle, lead to a modification (mutation) that results in the development of cancer or in premature aging. (news-medical.net)