DNA Damage: Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.DNA Repair: The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.DNA Adducts: The products of chemical reactions that result in the addition of extraneous chemical groups to DNA.Ultraviolet Rays: That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.Xeroderma Pigmentosum Group A Protein: A ZINC FINGER MOTIF protein that recognizes and interacts with damaged DNA. It is a DNA-binding protein that plays an essential role in NUCLEOTIDE EXCISION REPAIR. Mutations in this protein are associated with the most severe form of XERODERMA PIGMENTOSUM.Pyrimidine Dimers: Dimers found in DNA chains damaged by ULTRAVIOLET RAYS. They consist of two adjacent PYRIMIDINE NUCLEOTIDES, usually THYMINE nucleotides, in which the pyrimidine residues are covalently joined by a cyclobutane ring. These dimers block DNA REPLICATION.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Genome, Viral: The complete genetic complement contained in a DNA or RNA molecule in a virus.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Xeroderma Pigmentosum: A rare, pigmentary, and atrophic autosomal recessive disease. It is manifested as an extreme photosensitivity to ULTRAVIOLET RAYS as the result of a deficiency in the enzyme that permits excisional repair of ultraviolet-damaged DNA.Endonucleases: Enzymes that catalyze the hydrolysis of the internal bonds and thereby the formation of polynucleotides or oligonucleotides from ribo- or deoxyribonucleotide chains. EC 3.1.-.DNA Repair Enzymes: Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.DNA: 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).Nucleotides: The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)Xeroderma Pigmentosum Group D Protein: A DNA helicase that is a component of TRANSCRIPTION FACTOR TFIIH. It plays an essential role in NUCLEOTIDE EXCISION REPAIR, and mutations in this protein are associated with XERODERMA PIGMENTOSUM.Ataxia Telangiectasia Mutated Proteins: A group of PROTEIN-SERINE-THREONINE KINASES which activate critical signaling cascades in double strand breaks, APOPTOSIS, and GENOTOXIC STRESS such as ionizing ultraviolet A light, thereby acting as a DNA damage sensor. These proteins play a role in a wide range of signaling mechanisms in cell cycle control.Transcription Factor TFIIH: A general transcription factor that is involved in basal GENETIC TRANSCRIPTION and NUCLEOTIDE EXCISION REPAIR. It consists of nine subunits including ATP-DEPENDENT DNA HELICASES; CYCLIN H; and XERODERMA PIGMENTOSUM GROUP D PROTEIN.Endodeoxyribonucleases: A group of enzymes catalyzing the endonucleolytic cleavage of DNA. They include members of EC 3.1.21.-, EC 3.1.22.-, EC 3.1.23.- (DNA RESTRICTION ENZYMES), EC 3.1.24.- (DNA RESTRICTION ENZYMES), and EC 3.1.25.-.Polycyclic Hydrocarbons, Aromatic: A major group of unsaturated cyclic hydrocarbons containing two or more rings. The vast number of compounds of this important group, derived chiefly from petroleum and coal tar, are rather highly reactive and chemically versatile. The name is due to the strong and not unpleasant odor characteristic of most substances of this nature. (From Hawley's Condensed Chemical Dictionary, 12th ed, p96)DNA Helicases: Proteins that catalyze the unwinding of duplex DNA during replication by binding cooperatively to single-stranded regions of DNA or to short regions of duplex DNA that are undergoing transient opening. In addition DNA helicases are DNA-dependent ATPases that harness the free energy of ATP hydrolysis to translocate DNA strands.Tumor Suppressor Protein p53: Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.DNA Replication: The process by which a DNA molecule is duplicated.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Cockayne Syndrome: A syndrome characterized by multiple system abnormalities including DWARFISM; PHOTOSENSITIVITY DISORDERS; PREMATURE AGING; and HEARING LOSS. It is caused by mutations of a number of autosomal recessive genes encoding proteins that involve transcriptional-coupled DNA REPAIR processes. Cockayne syndrome is classified by the severity and age of onset. Type I (classical; CSA) is early childhood onset in the second year of life; type II (congenital; CSB) is early onset at birth with severe symptoms; type III (xeroderma pigmentosum; XP) is late childhood onset with mild symptoms.DNA Glycosylases: A family of DNA repair enzymes that recognize damaged nucleotide bases and remove them by hydrolyzing the N-glycosidic bond that attaches them to the sugar backbone of the DNA molecule. The process called BASE EXCISION REPAIR can be completed by a DNA-(APURINIC OR APYRIMIDINIC SITE) LYASE which excises the remaining RIBOSE sugar from the DNA.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Checkpoint Kinase 2: Enzyme activated in response to DNA DAMAGE involved in cell cycle arrest. The gene is located on the long (q) arm of chromosome 22 at position 12.1. In humans it is encoded by the CHEK2 gene.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Carcinogens, Environmental: Carcinogenic substances that are found in the environment.Genome, Human: 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.Comet Assay: A genotoxicological technique for measuring DNA damage in an individual cell using single-cell gel electrophoresis. Cell DNA fragments assume a "comet with tail" formation on electrophoresis and are detected with an image analysis system. Alkaline assay conditions facilitate sensitive detection of single-strand damage.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.DNA-(Apurinic or Apyrimidinic Site) Lyase: A DNA repair enzyme that catalyses the excision of ribose residues at apurinic and apyrimidinic DNA sites that can result from the action of DNA GLYCOSYLASES. The enzyme catalyzes a beta-elimination reaction in which the C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate. This enzyme was previously listed under EC 184.108.40.206.Tumor Suppressor Proteins: Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.DNA Methylation: Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.Radiation, Ionizing: ELECTROMAGNETIC RADIATION or particle radiation (high energy ELEMENTARY PARTICLES) capable of directly or indirectly producing IONS in its passage through matter. The wavelengths of ionizing electromagnetic radiation are equal to or smaller than those of short (far) ultraviolet radiation and include gamma and X-rays.Replication Protein A: A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Ficusin: A naturally occurring furocoumarin, found in PSORALEA. After photoactivation with UV radiation, it binds DNA via single and double-stranded cross-linking.Benzopyrenes: A class of chemicals that contain an anthracene ring with a naphthalene ring attached to it.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Recombination, Genetic: Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.Transcription Factors, TFII: The so-called general transcription factors that bind to RNA POLYMERASE II and that are required to initiate transcription. They include TFIIA; TFIIB; TFIID; TFIIE; TFIIF; TFIIH; TFII-I; and TFIIJ. In vivo they apparently bind in an ordered multi-step process and/or may form a large preinitiation complex called RNA polymerase II holoenzyme.Dose-Response Relationship, Radiation: The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation.7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide: 7,8,8a,9a-Tetrahydrobenzo(10,11)chryseno (3,4-b)oxirene-7,8-diol. A benzopyrene derivative with carcinogenic and mutagenic activity.Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Adenosine Triphosphatases: A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Deoxyguanosine: A nucleoside consisting of the base guanine and the sugar deoxyribose.DNA Polymerase beta: A DNA repair enzyme that catalyzes DNA synthesis during base excision DNA repair. EC 220.127.116.11.Methyl Methanesulfonate: An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA.Proliferating Cell Nuclear Antigen: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.GuanineBase Pair Mismatch: The presence of an uncomplimentary base in double-stranded DNA caused by spontaneous deamination of cytosine or adenine, mismatching during homologous recombination, or errors in DNA replication. Multiple, sequential base pair mismatches lead to formation of heteroduplex DNA; (NUCLEIC ACID HETERODUPLEXES).Deoxyribodipyrimidine Photo-Lyase: An enzyme that catalyzes the reactivation by light of UV-irradiated DNA. It breaks two carbon-carbon bonds in PYRIMIDINE DIMERS in DNA.DNA, Fungal: Deoxyribonucleic acid that makes up the genetic material of fungi.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Trichothiodystrophy Syndromes: Autosomal recessive neuroectodermal disorders characterized by brittle sulfur-deficient hair associated with impaired intellect, decreased fertility, and short stature. It may include nail dystrophy, ICHTHYOSIS, and photosensitivity correlated with a NUCLEOTIDE EXCISION REPAIR defect. All individuals with this disorder have a deficiency of cysteine-rich KERATIN-ASSOCIATED PROTEINS found in the interfilamentous matrix. Photosensitive trichothiodystrophy can be caused by mutation in at least 2 separate genes: ERCC2 PROTEIN gene and the related ERCC3. Nonphotosensitive trichothiodystrophy can be caused by mutation in the TTDN1 gene.Genomic Instability: An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.Nucleic Acid Conformation: The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.Cloning, Molecular: 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.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.N-Glycosyl Hydrolases: A class of enzymes involved in the hydrolysis of the N-glycosidic bond of nitrogen-linked sugars.Cell Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Fungal Proteins: Proteins found in any species of fungus.DNA Ligases: Poly(deoxyribonucleotide):poly(deoxyribonucleotide)ligases. Enzymes that catalyze the joining of preformed deoxyribonucleotides in phosphodiester linkage during genetic processes during repair of a single-stranded break in duplex DNA. The class includes both EC 18.104.22.168 (ATP) and EC 22.214.171.124 (NAD).Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.DNA Repair-Deficiency Disorders: Disorders resulting from defective DNA REPAIR processes or the associated cellular responses to DNA DAMAGE.DNA Breaks, Single-Stranded: Interruptions in one of the strands of the sugar-phosphate backbone of double-stranded DNA.ThymineCross-Linking Reagents: Reagents with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between side chains of amino acids in proteins; the locations of naturally reactive areas within proteins can thereby be identified; may also be used for other macromolecules, like glycoproteins, nucleic acids, or other.DNA-Directed DNA Polymerase: DNA-dependent DNA polymerases found in bacteria, animal and plant cells. During the replication process, these enzymes catalyze the addition of deoxyribonucleotide residues to the end of a DNA strand in the presence of DNA as template-primer. They also possess exonuclease activity and therefore function in DNA repair.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases.DNA Breaks, Double-Stranded: Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.Kinetics: The rate dynamics in chemical or physical systems.DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.Oligonucleotides: Polymers made up of a few (2-20) nucleotides. In molecular genetics, they refer to a short sequence synthesized to match a region where a mutation is known to occur, and then used as a probe (OLIGONUCLEOTIDE PROBES). (Dorland, 28th ed)Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Psoralens: Linear furanocoumarins which are found in many PLANTS, especially UMBELLIFERAE and RUTACEAE, as well as PSORALEA from which they were originally discovered. They can intercalate DNA and, in an UV-initiated reaction of the furan portion, alkylate PYRIMIDINES, resulting in PHOTOSENSITIVITY DISORDERS.Adenine NucleotidesRadiation Tolerance: The ability of some cells or tissues to survive lethal doses of IONIZING RADIATION. Tolerance depends on the species, cell type, and physical and chemical variables, including RADIATION-PROTECTIVE AGENTS and RADIATION-SENSITIZING AGENTS.Deoxyribonuclease (Pyrimidine Dimer): An enzyme which catalyzes an endonucleolytic cleavage near PYRIMIDINE DIMERS to produce a 5'-phosphate product. The enzyme acts on the damaged DNA strand, from the 5' side of the damaged site.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Oligonucleotide Array Sequence Analysis: 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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Blotting, Southwestern: A method that is used to detect DNA-protein interactions. Proteins are separated by electrophoresis and blotted onto a nitrocellulose membrane similar to Western blotting (BLOTTING, WESTERN) but the proteins are identified when they bind labeled DNA PROBES (as with Southern blotting (BLOTTING, SOUTHERN)) instead of antibodies.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.DNA, Single-Stranded: A single chain of deoxyribonucleotides that occurs in some bacteria and viruses. It usually exists as a covalently closed circle.Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Flap Endonucleases: Endonucleases that remove 5' DNA sequences from a DNA structure called a DNA flap. The DNA flap structure occurs in double-stranded DNA containing a single-stranded break where the 5' portion of the downstream strand is too long and overlaps the 3' end of the upstream strand. Flap endonucleases cleave the downstream strand of the overlap flap structure precisely after the first base-paired nucleotide, creating a ligatable nick.2-Acetylaminofluorene: A hepatic carcinogen whose mechanism of activation involves N-hydroxylation to the aryl hydroxamic acid followed by enzymatic sulfonation to sulfoxyfluorenylacetamide. It is used to study the carcinogenicity and mutagenicity of aromatic amines.Schizosaccharomyces pombe Proteins: Proteins obtained from the species Schizosaccharomyces pombe. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Chromatin: The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.Models, Genetic: Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.Uracil-DNA Glycosidase: An enzyme that catalyzes the HYDROLYSIS of the N-glycosidic bond between sugar phosphate backbone and URACIL residue during DNA synthesis.Bacterial Proteins: Proteins found in any species of bacterium.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Genes, Fungal: The functional hereditary units of FUNGI.Guanine NucleotidesDNA, Viral: Deoxyribonucleic acid that makes up the genetic material of viruses.RNA, Messenger: 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.Alkylation: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Genetic Complementation Test: A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.Polymorphism, Genetic: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Time Factors: Elements of limited time intervals, contributing to particular results or situations.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.Smoking: Inhaling and exhaling the smoke of burning TOBACCO.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.TATA-Binding Protein Associated Factors: Factors that associate with TATA-BOX BINDING PROTEIN. Many of them are components of TRANSCRIPTION FACTOR TFIIDDNA, Neoplasm: DNA present in neoplastic tissue.Gamma Rays: Penetrating, high-energy electromagnetic radiation emitted from atomic nuclei during NUCLEAR DECAY. The range of wavelengths of emitted radiation is between 0.1 - 100 pm which overlaps the shorter, more energetic hard X-RAYS wavelengths. The distinction between gamma rays and X-rays is based on their radiation source.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.DNA Mismatch Repair: A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the BASE PAIR MISMATCH and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. (from Oxford Dictionary of Biochemistry and Molecular Biology, 2001)Cell Line, Tumor: A cell line derived from cultured tumor cells.Purine Nucleotides: Purines attached to a RIBOSE and a phosphate that can polymerize to form DNA and RNA.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Sequence Alignment: 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.Single-Strand Specific DNA and RNA Endonucleases: Enzymes that catalyze the endonucleolytic cleavage of single-stranded regions of DNA or RNA molecules while leaving the double-stranded regions intact. They are particularly useful in the laboratory for producing "blunt-ended" DNA molecules from DNA with single-stranded ends and for sensitive GENETIC TECHNIQUES such as NUCLEASE PROTECTION ASSAYS that involve the detection of single-stranded DNA and RNA.Poly(ADP-ribose) Polymerases: Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.Sequence Homology, Nucleic Acid: 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.Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.Nucleic Acid Hybridization: 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)Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.Cell-Free System: A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166)Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Promoter Regions, Genetic: 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.Homologous Recombination: An exchange of DNA between matching or similar sequences.Acetoxyacetylaminofluorene: An alkylating agent that forms DNA ADDUCTS at the C-8 position in GUANINE, resulting in single strand breaks. It has demonstrated carcinogenic action.Photobiology: The branch of biology dealing with the effect of light on organisms.Oligodeoxyribonucleotides: A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.Ethylnitrosourea: A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.Benzo(a)pyrene: A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke.Exodeoxyribonucleases: A family of enzymes that catalyze the exonucleolytic cleavage of DNA. It includes members of the class EC 3.1.11 that produce 5'-phosphomonoesters as cleavage products.Skin Neoplasms: Tumors or cancer of the SKIN.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.DNA-Formamidopyrimidine Glycosylase: A DNA repair enzyme that is an N-glycosyl hydrolase with specificity for DNA-containing ring-opened N(7)-methylguanine residues.UracilCarbon-Oxygen Lyases: Enzymes that catalyze the cleavage of a carbon-oxygen bond by means other than hydrolysis or oxidation. EC 4.2.Genetic Variation: Genotypic differences observed among individuals in a population.Mitomycin: An antineoplastic antibiotic produced by Streptomyces caespitosus. It is one of the bi- or tri-functional ALKYLATING AGENTS causing cross-linking of DNA and inhibition of DNA synthesis.Cricetulus: A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Genes: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.RNA Polymerase II: A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. It functions in the nucleoplasmic structure and transcribes DNA into RNA. It has different requirements for cations and salt than RNA polymerase I and is strongly inhibited by alpha-amanitin. EC 126.96.36.199.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.DNA Restriction Enzymes: Enzymes that are part of the restriction-modification systems. They catalyze the endonucleolytic cleavage of DNA sequences which lack the species-specific methylation pattern in the host cell's DNA. Cleavage yields random or specific double-stranded fragments with terminal 5'-phosphates. The function of restriction enzymes is to destroy any foreign DNA that invades the host cell. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms. They are also used as tools for the systematic dissection and mapping of chromosomes, in the determination of base sequences of DNAs, and have made it possible to splice and recombine genes from one organism into the genome of another. EC 3.21.1.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Carcinogens: Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.Nitrofurazone: A topical anti-infective agent effective against gram-negative and gram-positive bacteria. It is used for superficial WOUNDS AND INJURIES and skin infections. Nitrofurazone has also been administered orally in the treatment of TRYPANOSOMIASIS.Antineoplastic Agents, Alkylating: A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026)S Phase: Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.Aphidicolin: An antiviral antibiotic produced by Cephalosporium aphidicola and other fungi. It inhibits the growth of eukaryotic cells and certain animal viruses by selectively inhibiting the cellular replication of DNA polymerase II or the viral-induced DNA polymerases. The drug may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon non-multiplying cells.DNA Polymerase I: A DNA-dependent DNA polymerase characterized in prokaryotes and may be present in higher organisms. It has both 3'-5' and 5'-3' exonuclease activity, but cannot use native double-stranded DNA as template-primer. It is not inhibited by sulfhydryl reagents and is active in both DNA synthesis and repair. EC 188.8.131.52.Nucleic Acid Heteroduplexes: Double-stranded nucleic acid molecules (DNA-DNA or DNA-RNA) which contain regions of nucleotide mismatches (non-complementary). In vivo, these heteroduplexes can result from mutation or genetic recombination; in vitro, they are formed by nucleic acid hybridization. Electron microscopic analysis of the resulting heteroduplexes facilitates the mapping of regions of base sequence homology of nucleic acids.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Rad51 Recombinase: A Rec A recombinase found in eukaryotes. Rad51 is involved in DNA REPAIR of double-strand breaks.Aging, Premature: Changes in the organism associated with senescence, occurring at an accelerated rate.Hair Diseases: Diseases affecting the orderly growth and persistence of hair.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Blotting, Southern: 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.Genes, p53: Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.DNA Polymerase II: A DNA-dependent DNA polymerase characterized in E. coli and other lower organisms. It may be present in higher organisms and has an intrinsic molecular activity only 5% of that of DNA Polymerase I. This polymerase has 3'-5' exonuclease activity, is effective only on duplex DNA with gaps or single-strand ends of less than 100 nucleotides as template, and is inhibited by sulfhydryl reagents. EC 184.108.40.206.Schizosaccharomyces: A genus of ascomycetous fungi of the family Schizosaccharomycetaceae, order Schizosaccharomycetales.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Rad52 DNA Repair and Recombination Protein: A DNA-binding protein that mediates DNA REPAIR of double strand breaks, and HOMOLOGOUS RECOMBINATION.Transcription Factor TFIID: The major sequence-specific DNA-binding component involved in the activation of transcription of RNA POLYMERASE II. It was originally described as a complex of TATA-BOX BINDING PROTEIN and TATA-BINDING PROTEIN ASSOCIATED FACTORS. It is now know that TATA BOX BINDING PROTEIN-LIKE PROTEINS may take the place of TATA-box binding protein in the complex.Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids.Adenine: A purine base and a fundamental unit of ADENINE NUCLEOTIDES.Methylnitronitrosoguanidine: A nitrosoguanidine derivative with potent mutagenic and carcinogenic properties.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Base Pairing: Pairing of purine and pyrimidine bases by HYDROGEN BONDING in double-stranded DNA or RNA.DNA Polymerase III: A DNA-dependent DNA polymerase characterized in E. coli and other lower organisms but may be present in higher organisms. Use also for a more complex form of DNA polymerase III designated as DNA polymerase III* or pol III* which is 15 times more active biologically than DNA polymerase I in the synthesis of DNA. This polymerase has both 3'-5' and 5'-3' exonuclease activities, is inhibited by sulfhydryl reagents, and has the same template-primer dependence as pol II. EC 220.127.116.11.Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (CODON, TERMINATOR). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, TRANSFER) complementary to all codons. These codons are referred to as unassigned codons (CODONS, NONSENSE).Hypoxanthine Phosphoribosyltransferase: An enzyme that catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate and hypoxanthine, guanine, or 6-mercaptopurine to the corresponding 5'-mononucleotides and pyrophosphate. The enzyme is important in purine biosynthesis as well as central nervous system functions. Complete lack of enzyme activity is associated with the LESCH-NYHAN SYNDROME, while partial deficiency results in overproduction of uric acid. EC 18.104.22.168.
Nucleotide excision repair (NER) repairs damaged DNA which commonly consists of bulky, helix-distorting damage, such as ... double-strand breaks or adducts stalling the replication forks, are among known stimulation signals for a global response to ... Molecular and Cellular Biology portal Accelerated aging disease Aging DNA Cell cycle DNA damage (naturally occurring) DNA ... 2006). "Increased genomic instability is not a prerequisite for shortened life span in DNA repair deficient mice". Mutation ...
... as well as to a method for ascertaining genetic and/or epigenetic parameters of genes associated with DNA repair. ... to oligonucleotides and/or PNA-oligomers for detecting the cytosine methylation state of genes associated with DNA repair which ... The present invention relates to the chemically modified genomic sequences of genes associated with DNA repair, ... Nucleotide excision repair (NER) removes a wide diversity of lesions, which include UN-induced lesions, bulky chemical adducts ...
... cellular survival and cellular longevity. Oxidative stress impacts almost all acute and chronic progressive disorders and on a ... Open Access journal that publishes original research and review articles dealing with the cellular and molecular mechanisms of ... cellular basis is intimately linked to aging, cardiovascular disease, cancer, immune function, metabolism and neurodegeneration ... Oxidative Medicine and Cellular Longevity is a unique peer-reviewed, ...
Two DNA repair pathways deal with the majority of lesions: base excision repair (BER) and nucleotide excision repair (NER). The ... The NER pathway is more versitile, recognizing helix-distorting lesions, such as UV-induced damage and bulky adducts. Xeroderma ... For NHEJ proteins, similar isoforms of DNA-PKcs and the Ku70 subunit were detected in all cellular compartments. On the other ... Genomic Structural Variation , Greece , Phylogeography , Sequence Analysis, DNA , Translocation, Genetic ...
... to a group of diseases due to damages to the nucleotide excision repair mechanism which cannot effectively repair DNA damage ... The NER pathway is more versitile, recognizing helix-distorting lesions, such as UV-induced damage and bulky adducts. Xeroderma ... Aging , Animals , Antioxidants , Catalase , Cats , Cellular Senescence , Cell Cycle , Cell Cycle Checkpoints , Cell Death , ... This study unfolds new possible roles for XPC, aside from its established roles in genomic instability, in metabolic adaptation ...
Adimoolam S, Ford JM p53 and regulation of DNA damage recognition during nucleotide excision repair. DNA Repair (Amst), 2: 947- ... such as those induced by UV light and chemicals that give rise to bulky DNA adducts and DNA cross-links. A stretch of ... Chu G Expression of the p48 xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair. Proc Natl ... This again indicates that p53-mediated apoptosis upon the presence of DNA damage might be the critical cellular response ...
Over the past few years, an additional, more global role has emerged for the contribution of DNA damage and genomic instability ... The former is generally mediated by base excision repair (BER) or nucleotide excision repair (NER), the latter by non- ... DNA damage remains a leading, though still debated theory. Unlike most other types of age-related cellular damage, which can ... 8-oxo-Guanine and related single-stranded DNA lesions are generally repaired by BER, while bulkier lesions are subject to NER ( ...
Inhibiting its enzyme activity with small molecules thus achieves synthetic lethality by preventing unwanted DNA repair in the ... we shall discuss how transcription and DNA repair are so intricately linked that disturbance by PARP1 enzymatic inhibition, ... is an ADP-ribosylating enzyme essential for initiating various forms of DNA repair. ... Large adducts that distort DNA structure such as thymine dimers formed by UV irradiation require nucleotide excision repair ( ...
Nucleotide excision repair (NER) is a versatile DNA repair pathway which can be activated in response to a broad spectrum of UV ... DNA damage, such as bulky adducts, including cyclobutane-pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs). Based on the ... global genomic NER (GG-NER), involved in the ablation of damage throughout the whole genome regardless of the transcription ... The UBQLN substrates reveal great diversity and impact a wide range of cellular functions. For decades, researchers have been ...
... to delineate chromatin alterations in response to DNA damage by focusing on the well-characterized Nucleotide Excision Repair ( ... We also highlight how these methods have provided key mechanistic insight into histone dynamics coupled to repair in mammals, ... our understanding of the mechanisms underlying chromatin disorganization upon damage detection and re-assembly after repair. ... and histone chaperones function to mobilize histones during repair. ...
We will discuss the role of histone modifications as well as their displacement or exchange in nucleotide excision repair and ... Here, we discuss current knowledge on chromatin remodelling with respect to the cellular response to DNA damage, with emphasis ... DNA repair. For both damage signalling and repair, chromatin remodelling is most likely a prerequisite. ... These damaging agents can induce a wide variety of lesions in the DNA, such as double strand breaks, single strand breaks, ...
... cellular, organismal aspects of gerontological research and in diagnosis, treatment, evaluation and educational aspects of ... Such DNA adducts are mainly repaired by the nucleotide excision repair pathway. Interestingly, the formation of DNA adducts by ... This theory was followed by the DNA damage theory of aging , which proposes that the accumulation of genomic instability in ... The nucleotide excision repair (NER) is the main DNA repair system for the removal of bulky and helix distorting lesions in DNA ...
... which is interpreted as a basic deficiency in nucleotide excision repair. HBxmut120 (Glu to Val) was defective in binding to ... We conclude that HBx may act as the promoting factor by inhibiting DNA repair causing DNA damage and accumulation of errors, ... is a multifunctional protein that can modulate various cellular processes and plays a crucial role in the pathogenesis of HCC. ... a basal transcriptional factor and an integral component of DNA excision repair. In this study, the functional relevance of ...
There is also evidence that the XPC-hHR23B protein complex may initiate recognition of DNA damage for the global genomic repair ... The most versatile and important one is the NER pathway, which detects and removes bulky DNA adducts, including those induced ... A critical cellular response that counteracts the carcinogenic effects of DNA damage is DNA repair. As stated earlier, there ... At least four pathways of DNA repair operate on specific types of damaged DNA. Base excision repair (BER) operates on small ...
... refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode ... Nucleotide excision repair (NER), which repairs damage affecting longer strands of 2-30 bases. This process recognizes bulky, ... specifically double strand breaks or adducts stalling the replication forks, are among known stimulation signals for a global ... Types of damage. There are four main types of damage to DNA due to endogenous cellular processes: * oxidation of bases [e.g. 8- ...
... with the level of DNA damage and repair, accessed by comet and micronucleus test, in 51 COPD patients and 51 controls. ... showed higher DNA damage by comet assay. The residual damage was higher for COPD with risk allele in the four genes. In COPD ... To assess the susceptibility to exogenous DNA damage, the cells were treated with methyl methanesulphonate for 1-h or 3-h. ... After 3-h treatment the % residual damage was calculated assuming the value of 1-h treatment as 100%. The cytogenetic damage ...
The global genomic nucleotide excision repair (ggNER) detected using alkaline electrophoresis. A: Representative alkaline ... Cellular genomic DNA constantly suffers from damage induced by various external genotoxic agents and endogenous metabolic ... the global genome (gg) NER and the transcription-coupled repair (TCR). TCR can preferentially remove the bulky DNA lesions ... pyrene DNA adducts. The relevance of this repair pathway is indicated by the observation that defected NER genes can result in ...
Efficient repair of bulky anti-BPDE DNA adducts from non-transcribed DNA strand requires functional p53 but not p21(waf1/cip1) ... indicating the role of p53 and not pRb in nucleotide excision repair (NER)... the modulation of NER by p53 may be independent ... Global genomic diversity of human papillomavirus type 6 (HPV6) based on 724 isolates and 190 complete genome sequences. MM ... repair, recombination, and amplification, which also involve the flanking cellular DNA.". ...
... nucleotide excision repair (NER) serves as the predominant DNA repair pathway for repairing bulky DNA adducts, involving both ... global genomic NER (GG-NER) and transcription-coupled NER (TC-NER) (37, 38). The strand bias that we observed in this study ... Several cellular pathways exist for repairing DNA lesions caused by carcinogens (36). Of these, ... Recognition of damaged DNA: Structure and dynamic markers. Med. Res. Rev. 32, 659-683 (2012).. ...
NER is the major repair pathway for bulky DNA damage, including PAH-DNA adducts and exocyclic propanodeoxyguanine adducts (22, ... can bond with proteins and have been found to cause an inhibitory effect on nucleotide excision repair (NER) (14, 15). We ... Acr-DNA Adduct Analysis.. Acr-DNA adducts formed in cells treated with Acr (0-100 μM) and in purified genomic DNA modified with ... Our findings that Acr greatly inhibit cellular repair capacity to remove BPDE-DNA adducts in human lung cells strongly suggest ...
As with most bulky adducts, dA-AL adducts normally would be excised by global genomic nucleotide excision repair. However, the ... Because of the lifelong persistence of mutagenic DNA-AL-I adducts in target tissues and irreversible damage to the proximal ... 2008) Cellular mechanisms of tumour suppression by the retinoblastoma gene. Nat Rev Cancer 8:671-682. ... by global-genome nucleotide excision repair accounts for the high mutagenicity and persistence of aristolactam-DNA adducts. ...
... including those for nucleotide excision repair, are expressed; however, later in the SOS response, error-prone translesion DNA ... these modifications result in a more flexible and open active site that may facilitate TLS over DNA damage due to bulky adducts ... Y-Family DNA polymerases and their role in tolerance of cellular DNA damage. . Nat. Rev. Mol. Cell Biol.. 13. , 141. -. 152. . ... Antimicrobial resistance: Global report on surveillance, 2014. (. 2014. ) World Health Organization. , Geneva. .. Livermore. D ...
Genotoxic exposure to tobacco carcinogens resulting in DNA damage is an important mechanism of oral squamous cell carcinoma ( ... Nucleotide Excision Repair (NER) pathway removes bulky DNA adducts, generated from tobacco exposure thereby playing a major ... Multiple cellular DNA repair pathways are operational to rectify/attenuate deleterious effects of cellular DNA damage. Amongst ... Genomic DNA treated with SssI methylase served as positive control and blood DNA samples were used as negative control for MSP ...
DNA Damage Response (DDR) including different repair pathways. Nucleotide excision repair (NER) is versatile repair process, ... Nucleotide excision repair (NER) is versatile repair process, eliminating helix-distorting lesions, e.g. bulky adducts and sun- ... Efficient recognition and repair of DNA damage, however, is complicated by the fact that genomic DNA is packaged, through ... Summary The success of modern medical treatments such as cellular therapy and targeted treatments requires appropriate tools ...
Nucleotide excision repair (NER) repairs damaged DNA which commonly consists of bulky, helix-distorting damage, such as ... double-strand breaks or adducts stalling the replication forks, are among known stimulation signals for a global response to ... Molecular and Cellular Biology portal Accelerated aging disease Aging DNA Cell cycle DNA damage (naturally occurring) DNA ... 2006). "Increased genomic instability is not a prerequisite for shortened life span in DNA repair deficient mice". Mutation ...
Nucleotide Excision Repair (NER), Mismatch Repair (MMR) and Base Excision Repair (BER). The impact of ERCC1 expression on ... unless adducts from genomic DNA are repaired . Even a single DNA cross-link, if not repairable, can be lethal . There ... Cellular Response to Platin-Induced DNA-Damage. DNA damage, e.g. induced by platin-compounds, is first recognized by ATM and ... Platinum cytotoxicity is based on forming bulky DNA adducts by chemically altering DNA bases by covalent binding of platinum [ ...
PathwaysSingle nucleotide poEnzymesGenesDeficientSynthesisOxidativeMaintenance of genomicMutagenesisLesionProcessesInstabilityExogenous DNA damagiGeneticGenomeMammalianTranscriptionalMutationResponse to DNA damageTypes of DNA lesionsSpontaneousIonizing radiationHomologousFunctionalConstantlyTumorIntegrityCPDsForm covalentAssaysStructurallyCarcinogensBreaks are repairedBenzoCyclobutaneMethylationProteinInhibitionGenotoxic agentsChromatinProteinsDefectsMetabolicNHEJTP53UltravioletStrand
- NER is a complex process, consisting of two distinct pathways, i.e. , transcription coupled repair eliminating DNA damage present in the transcribed strand of active genes and global genome repair that removes lesions throughout the genome and the nontranscribed strand of active genes. (aacrjournals.org)
- Based on the genomic position of the lesion, two sub-pathways can be defined: (I) global genomic NER (GG-NER), involved in the ablation of damage throughout the whole genome regardless of the transcription activity of the damaged DNA locus, and (II) transcription-coupled NER (TC-NER), activated at DNA regions where RNAPII-mediated transcription takes place. (ynsqex.icu)
- At least four major damage repair pathways operate in mammals: NER, base excision repair (BER), homologous recombination (HR) and end joining (EJ). (biomedcentral.com)
- This paper covers some of the DNA repair pathways affecting liver homeostasis with age using rodents as model systems. (hindawi.com)
- These mechanisms include insertional mutagenesis upon integration, trans-activation of the cellular genes, activation of signaling pathways, inactivation of tumor suppressor proteins, synergy with environmental carcinogenesis and host immune response. (biomedcentral.com)
- Advances in the identification of new polymorphisms and in high-throughput genotyping techniques will facilitate the analysis of multiple genes in multiple DNA repair pathways. (medsci.org)
- In eukaryotic cells, there are two sub-pathways of nucleotide excision repair (NER), the global genome (gg) NER and the transcription-coupled repair (TCR). (biomedcentral.com)
- In eukaryotic cells there are multiple conserved DNA repair pathways including nucleotide excision repair (NER), which is a DNA repair mechanism removing a variety of helix-distorting DNA lesions including ultraviolet radiation (UV)-induced cyclobutane pyrimidine dimers (CPD), 6-4 pyrimidine pyrimidone photoproducts [(6-4)PPs], and cigarette smoke-induced benzo[a]pyrene DNA adducts. (biomedcentral.com)
- Multiple cellular DNA repair pathways are operational to rectify/attenuate deleterious effects of cellular DNA damage. (omicsonline.org)
- Amongst major DNA repair pathways, Nucleotide excision repair [NER] is an important pathway which removes structurally diverse lesions such as bulky chemical adducts arising as a result of exposure to tobacco carcinogens [ 4 ]. (omicsonline.org)
- PMID:11850621 Falck J, Petrini JH, Williams BR, Lukas J, Bartek J (2002) The DNA damage-dependent intra-S phase checkpoint is regulated by parallel pathways. (curie.fr)
- After exposure to genotoxic agents, cells activate DNA damage response pathways consisting of a signaling cascade (cell cycle checkpoints), and of DNA repair processes able to recognize and remove a great number of DNA lesions [ 1 ]. (intechopen.com)
- We increased the amount of spontaneous DNA lesions using mutants deficient for different DNA repair pathways and measured mutation frequency in PolIV-proficient and -deficient backgrounds. (genetics.org)
- DNA lesions can be tolerated via different pathways, of which the two best studied are homologous recombination and replicative lesion bypass. (genetics.org)
- Direct measurement of DNA repair enzyme activities is important both for the basic study of cellular repair pathways as well as for potential new translational applications in their associated diseases. (bvsalud.org)
- 10. Use of a set of oligomer probes comprising at least ten of the oligomers according to any of claims 6 through 9 for detecting the cytosine methylation state and/or single nucleotide polymorphisms (SNPs) in a chemically pretreated genomic DNA according to claim 1 or a chemically pretreated DNA of genes according to claim 2. (google.com.au)
- Recent lung cancer studies have focused on identifying the effects of single nucleotide polymorphisms (SNPs) in candidate genes, among which DNA repair genes are increasingly being studied. (medsci.org)
- A growing body of literature, including observations of inter-individual differences in measures of DNA damage, suggests that these polymorphisms may alter the functional properties of DNA repair enzymes. (medsci.org)
- The genes encoding three key enzymes in this repair pathway are: 8-oxoguanine DNA glycosylase ( OGG1 ), apurinic/apyrimidinic endonuclease ( APE1 / APEX1 ), and the X-ray repair cross complementing group 1 ( XRCC1 ). (biomedcentral.com)
- Based on reports of oxidative DNA damage induction by MAL and 4-hydroxy-2.5-dimethyl-3(2H) furanone (HDMF), these compounds were tested in the enhanced comet assay using repair enzymes to identify oxidative DNA damage. (gta-us.org)
- The present invention relates to the chemically modified genomic sequences of genes associated with DNA repair, to oligonucleotides and/or PNA-oligomers for detecting the cytosine methylation state of genes associated with DNA repair which are directed against the sequence, as well as to a method for. (google.com.au)
- 1. A nucleic acid comprising a sequence at least 18 bases in length of a segment of the chemically pretreated DNA of genes associated with DNA repair according to one of the sequences taken from the group of Seq. (google.com.au)
- ID No. 144 and sequences complementary thereto and/or chemically pretreated DNA of genes according to claim 2, wherein at least one oligomer according to any of the claims 3 through 5 is coupled to a solid phase. (google.com.au)
- Foi realizado o sequenciamento de alto desempenho utilizando a plataforma NextSeq (Illumina) para avaliar as regiões codificantes de 114 genes selecionados pela sua relevância em desordens dermatológicas, tumorigênese e fisiologia cutânea e resposta de dano ao DNA. (bvsalud.org)
- Variantes germinativas de significado incerto foram identificadas, em heterozigose, no DNA de leucócito de cinco dos seis pacientes avaliados ocorrendo nos genes DNAH11, PCDHB3, RGS22, SLC27A5, TTN e UGT2B10 e nenhuma das variantes identificadas apresentou perda de heterozigose do alelo selvagem nos tecidos tumorais. (bvsalud.org)
- The Xeroderma Pigmentosum (XP) syndrome occurs on base of biallelic inheritance of pathogenic germline variants of loss of function or function reduction in genes that plays role in nucleotide excision repair and translesion synthesis. (bvsalud.org)
- Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. (medsci.org)
- We identified a sufficient number of epidemiologic studies on lung cancer to conduct a meta-analysis for genetic polymorphisms in nucleotide excision repair pathway genes, focusing on xeroderma pigmentosum group A (XPA), excision repair cross complementing group 1 (ERCC1), ERCC2/XPD, ERCC4/XPF and ERCC5/XPG. (medsci.org)
- Several of the genes that are frequently lost or mutated have been identified, including genes that function to induce cell proliferation under specific circumstances (e.g. the ras and myc proto-oncogenes) and those which are programmed to halt proliferation in damaged cells (e.g. the TP53 and RB1 tumor suppressor genes). (medsci.org)
- About 150 human DNA repair genes have been identified to date [ 2 ], but the real number is probably higher, since less than 50% of known and putative genes have an identified function. (medsci.org)
- Novel, common polymorphisms in DNA repair genes are continuously being identified, and these polymorphisms may play a pivotal role in sporadic carcinogenesis. (medsci.org)
- Many genes that were initially shown to influence lifespan have turned out to be involved in DNA damage repair and protection. (bionity.com)
- We investigated a potential link between genetic polymorphisms in genes XRCC1 (Arg399Gln), OGG1 (Ser326Cys), XRCC3 (Thr241Met), and XRCC4 (Ile401Thr) with the level of DNA damage and repair, accessed by comet and micronucleus test, in 51 COPD patients and 51 controls. (biomedcentral.com)
- The residual damage was higher for COPD with risk allele in the four genes. (biomedcentral.com)
- The finding supports the hypothesis that variants in DNA repair genes could affect COPD susceptibility. (biomedcentral.com)
- TCR preferentially repairs the transcribed strand or transcribed genes compared to the untranscribed strand or silenced genes. (biomedcentral.com)
- Cyriac C, Sharma R, Binepal G, Panda N, Khullar M (2015) Epigenetic Modifications of Nucleotide Excision Repair Genes in Oral Squamous Cell Carcinoma. (omicsonline.org)
- XPC, XPB and XPD involved in removal of adducts caused by major classes of tobacco carcinogens and their contribution to OSCC Methylation status of NER genes was assessed using methylation specific PCR (MSP) in biopsies taken from 52 OSCC patients, their surrounding margins and 27 normal controls. (omicsonline.org)
- Epigenetic changes such as DNA methylation and histone modifications have been shown to silence key genes involved in cell proliferation, differentiation and genome integrity and thus may have a central role in oral tumorigenesis [ 1 ]. (omicsonline.org)
- Several critical genes participate in the NER process and have functions central to the ability of a cell to cope with different types of DNA damage and to maintain genomic integrity [ 5 ]. (omicsonline.org)
- and analyzing the sample for increased or decreased expression levels of at least three DNA repair genes as compared to a control cell that is not exposed to the potentially genotoxic or carcinogenic compound. (patentsencyclopedia.com)
- Remarkably, genome-wide mapping by ChIP-seq demonstrated that HOXC9 bound to 40% of these genes, including a large number of genes involved in neuronal differentiation, cell cycle progression and the DNA damage response. (biomedcentral.com)
- Our results demonstrate that HOXC9 coordinates diverse cellular processes associated with differentiation by directly activating and repressing the transcription of distinct sets of genes. (biomedcentral.com)
- Cancerous hyper-mutagenesis in p53 genes is possibly associated with transcriptional bypass of DNA lesions. (medecinesciences.org)
- Consequently, patients are deficient in correct DNA lesions mainly induced by ultraviolet radiation, present high sensitivity to solar radiation and increased risk for the development of multiple premalignant and malignant skin lesions. (bvsalud.org)
- In contrast, liver tumor response was primarily dependent on appropriate DNA repair, because Xpa -deficient mice were liver tumor prone. (aacrjournals.org)
- The association between defects in DNA repair and cancer was established by Cleaver in 1968 [ 3 ], who showed that xeroderma pigmentosum (XP) is caused by deficient nucleotide excision repair (NER). (medsci.org)
- Interestingly, the triplex-induced recombination was unaffected in cells deficient in DNA mismatch repair, challenging our previous model of a heteroduplex intermediate and supporting a model based on end joining. (asm.org)
- In both processes the injury is excised and the resulting gap is filled by DNA synthesis using the intact complementary strand as a template, enabling error-free DNA repair. (biomedcentral.com)
- This association may interfere with PCNA-dependent enzyme activities involved in DNA synthesis [ 18 , 19 ]. (intechopen.com)
- To receive news and publication updates for Oxidative Medicine and Cellular Longevity, enter your email address in the box below. (hindawi.com)
- Another very prominent type of endogenous DNA damage, oxidative DNA damage, is caused by reactive oxygen species (ROS), which are formed continuously as a consequence of normal aerobic metabolism during mitochondrial respiration but also by inflammatory responses. (hindawi.com)
- These damaging agents can induce a wide variety of lesions in the DNA, such as double strand breaks, single strand breaks, oxidative lesions and pyrimidine dimers. (biomedcentral.com)
- Essential cellular functions such as oxidative respiration and lipid peroxidation create reactive oxygen species that can damage DNA. (biomedcentral.com)
- OGG1 catalyzes the removal of 8-hydrodeoxy-guanine (8-OHdG), which has been considered as a key biomarker of oxidative DNA damage. (biomedcentral.com)
- Apurinic sites and oxidative damage are also highly enriched in transposable elements and other repetitive sequences. (springer.com)
- Other sources of AP-sites include spontaneous depurination and excision of non-oxidative base modifications, such as uracil. (springer.com)
- Ionizing radiation is one of the most relevant exogenous sources of high-level oxidative DNA damage and DNA strand breaks. (springer.com)
- Our genome is under constant attack by exogenous DNA insulting agents, such as UV light and chemical carcinogens, and by endogenous metabolic products, such as reactive oxidative species. (frontiersin.org)
- Base excision repair (BER) is instead involved in the removal of bases damaged by alkylating, or oxidative agents, while the repair of single and double strand breaks is performed through the pathway of homologous recombination, or via the non homologous end-joning (NHEJ) repair. (intechopen.com)
- In the enhanced comet assay positive comet findings for MAL were not confirmed, and only equivocal evidence of oxidative damage was found. (gta-us.org)
- Meanwhile, HDMF, produced positive results in the enhanced comet assay with formamidopyrimidine DNA glycosylase (FPG) enzyme digestion, indicative of its ability to produce DNA strand breakage via oxidative damage. (gta-us.org)
- Proper functioning of all living organisms depends on faithful maintenance of genomic information. (biomedcentral.com)
- In the current review we discuss a subset of these proteins involved in the direct maintenance of genomic stability, an important cellular process in the conservation of cellular viability and prevention of malignant transformation. (biomedcentral.com)
- In the current review, we discuss the roles of a subset of human SSBs in the maintenance of genomic stability, an essential consideration in the prevention of malignant transformation and loss of cellular viability. (biomedcentral.com)
- Most of these alterations, if not repaired, can result in genetic instability, mutagenesis and cell death. (medsci.org)
- The p48 subunit of UV-DDB is mutated in xeroderma pigmentosum group E. UV-DDB enhances nucleotide excision repair while suppressing UV-induced mutagenesis. (stanford.edu)
- DNA damage induced by UVA radiation: role in solar mutagenesis. (medecinesciences.org)
- DNA repair is characterized by an impressive high number of different proteins necessary to perform specialized biochemical reactions, which are different according to the type of lesion to be repaired [ 2 ]. (intechopen.com)
- Lesion bypass can be either error free or error prone when the correct or incorrect nucleotide, respectively, is incorporated opposite the damage. (genetics.org)
- As a response to DNA damage, essentially all organisms have developed elaborate DNA repair mechanisms to preserve the integrity of their genetic material: reversion, excision or tolerance of a lesion. (intechopen.com)
- These studies are the first to directly link deficiencies in MutY lesion detection with incomplete cellular repair. (bvsalud.org)
- The 2'-F-hydantoins in duplex DNA were found to be highly resistant to the glycosylase activity of Fpg and NEIL1 compared to the unmodified lesion substrates. (bvsalud.org)
- The distinct features of glycosylase processing of 2'-F-ribohydantoins and 2'-F-arabinohydantoins illustrate their utility to reveal structural insight into damage recognition and excision by NEIL and related glycosylases and provide opportunities for delineating the impact of lesion formation and repair in cells. (bvsalud.org)
- Among the different mechanisms that have been implicated in the aging process, DNA repair is one of the processes which have been suggested to play an important role. (hindawi.com)
- Among the wide variety of known DNA lesions, 8-oxo-deoxyguanosine (8oxoG) has received a lot of attention due to its mutagenicity and because of the possible correlation between its accumulation and pathological processes like cancer, degenerative diseases, and aging. (hindawi.com)
- To counteract the severe biological consequences of DNA lesions an intricate network of genome surveillance mechanisms or DNA damage response (DDR) processes has evolved. (biomedcentral.com)
- HBV X protein (HBx) is a multifunctional protein that can modulate various cellular processes and plays a crucial role in the pathogenesis of HCC. (biomedcentral.com)
- DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome . (bionity.com)
- DNA damage, due to environmental factors and normal metabolic processes inside the cell, occurs at a rate of 1,000 to 1,000,000 molecular lesions per cell per day. (bionity.com)
- When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur, including double-strand breaks and DNA crosslinkages (interstrand crosslinks or ICLs). (wikipedia.org)
- Play media The 2015 Nobel Prize in Chemistry was awarded to Tomas Lindahl, Paul Modrich, and Aziz Sancar for their work on the molecular mechanisms of DNA repair processes. (wikipedia.org)
- There are several types of damage to DNA due to endogenous cellular processes: oxidation of bases [e.g. 8-oxo-7,8-dihydroguanine (8-oxoG)] and generation of DNA strand interruptions from reactive oxygen species, alkylation of bases (usually methylation), such as formation of 7-methylguanosine, 1-methyladenine, 6-O-Methylguanine hydrolysis of bases, such as deamination, depurination, and depyrimidination. (wikipedia.org)
- The hydantoins are excellent substrates for the NEIL glycosylases in a variety of DNA contexts beyond canonical duplex DNA, implicating the potential impact of repair activity on a multitude of cellular processes. (bvsalud.org)
- Over the past few years, an additional, more global role has emerged for the contribution of DNA damage and genomic instability to the ageing process. (pubmedcentralcanada.ca)
- Recent work extends the impact of genomic defects to an age-associated deregulation of the epigenome (reviewed in ( Oberdoerffer and Sinclair 2007 )), suggesting that the accumulation of DNA damage and genomic instability with age may be a critical contributor to the ageing process, though perhaps in a more indirect and complex way than first proposed. (pubmedcentralcanada.ca)
- We discuss how human genetic studies as well as several investigations on mammalian models and simpler eukaryotic organisms have contributed to a better understanding of the involvement of DNA repair mechanisms in aging. (hindawi.com)
- In contrast to damaged lipids and proteins, damaged DNA, which carries the inherited genetic information of the cell, cannot be replaced. (hindawi.com)
- The integrity of genetic material of living organisms is constantly threatened by exposure to DNA-damaging agents. (aacrjournals.org)
- The heart of this defence system is formed by complementary DNA repair systems that cover most of the genetic insults. (biomedcentral.com)
- We found that PolIV performs an error-free bypass of DNA damage that accumulates in the alkA tag genetic background. (genetics.org)
- When the amount of cytotoxic alkylating DNA lesions is increased by the treatment with chemical alkylating agents, PolIV is required for survival in an alkA tag -proficient genetic background as well. (genetics.org)
- Due to close proximity of the mitochondrial DNA to the inner mitochondrial membrane, the mitochondrial genome is more heavily exposed to ROS than the nuclear DNA and therefore also more likely to experience DNA damage. (hindawi.com)
- We, and others have found that DNA damage and the concomitant repair process can induce genome-wide epigenetic changes, which may promote a variety of age-related transcriptional and functional changes. (pubmedcentralcanada.ca)
- The DNA repair ability of a cell is vital to the integrity of its genome and thus to its normal functioning and that of the organism. (bionity.com)
- DNA is subject to constant chemical modification and damage, which eventually results in variable mutation rates throughout the genome. (springer.com)
- Although detailed molecular mechanisms of DNA damage and repair are well understood, damage impact and execution of repair across a genome remain poorly defined. (springer.com)
- To bridge the gap between our understanding of DNA repair and mutation distributions, we developed a novel method, AP-seq, capable of mapping apurinic sites and 8-oxo-7,8-dihydroguanine bases at approximately 250-bp resolution on a genome-wide scale. (springer.com)
- We directly demonstrate that the accumulation rate of apurinic sites varies widely across the genome, with hot spots acquiring many times more damage than cold spots. (springer.com)
- This work demonstrates that oligonucleotide-mediated triplex formation can be recombinagenic, providing the basis for a potential strategy to direct genome modification by using high-affinity DNA binding ligands. (asm.org)
- DNA exists primarily as a duplex to stabilise and protect our genome. (biomedcentral.com)
- The human genome encodes both simple and higher order SSBs: the simple SSBs are represented by human single-stranded DNA binding proteins 1 and 2 (hSSB1 and 2) and the mitochondrial SSB (mtSSB), while higher order SSBs are represented by heterotrimeric RPA. (biomedcentral.com)
- It has been estimated that in an average mammalian cell ten to a hundred thousand DNA lesions are introduced each day [ 1 ]. (biomedcentral.com)
- Yeast and mammalian cells expressing HBx wt conferred hypersensitivity to UV irradiation, which is interpreted as a basic deficiency in nucleotide excision repair. (biomedcentral.com)
- In previous work, members of our group demonstrated that psoralen damage can be introduced into DNA within mammalian cells in a site-specific manner by linking psoralen to an oligonucleotide that is designed to form a triple helix ( 62 ). (asm.org)
- This is the predominant double-strand break repair pathway in mammalian cells. (curie.fr)
- PMID:9242410 Grawunder U, Wilm M, Wu X, Kulesza P, Wilson TE, Mann M, Lieber MR (1997) Activity of DNA ligase IV stimulated by complex formation with XRCC4 protein in mammalian cells. (curie.fr)
- Our study, together with the reported involvement of the mammalian PolIV homolog, Polκ, in similar activity, indicates that Y-family DNA polymerases from the DinB branch can be added to the list of evolutionarily conserved molecular mechanisms that counteract cytotoxic effects of DNA alkylation. (genetics.org)
- Histone acetylation renders chromatin accessible for transcriptional regulators and DNA binding factors, whereas histone and DNA methylation have the opposite effect, although certain types of histone methylation are linked to active transcription ( Kouzarides 2007 ). (pubmedcentralcanada.ca)
- Besides DNA repair, the importance of PARP1 as a transcriptional regulator is also well established. (mdpi.com)
- In this review, we will summarize the roles of PARP1 in DNA repair and transcriptional regulation. (mdpi.com)
- HBx is known to interact with DNA helicase components of TFIIH, a basal transcriptional factor and an integral component of DNA excision repair. (biomedcentral.com)
- Mono-ubiquitination and multi-ubiquitination play important roles in endocytosis, DNA repair, immune response, and transcriptional regulation, etc. (frontiersin.org)
- G (MT-ATP6) mutation in the mitochondrial DNA. (bvsalud.org)
- The level of DNA damage and/or mutation can be affected by changes in carcinogen activation, decreased ability to repair DNA, or a combination of these factors. (hindawi.com)
- Using AL-DNA adducts and TP53 mutation spectra as biomarkers, we conducted a molecular epidemiologic study of UUC in Taiwan, where the incidence of UUC is the highest reported anywhere in the world and where Aristolochia herbal remedies have been used extensively for many years. (pnas.org)
- Slow repair of pyrimidine dimers at p53 mutation hotspots in skin cancer. (medecinesciences.org)
- Here, we review the methods that have been developed over the years to delineate chromatin alterations in response to DNA damage by focusing on the well-characterized Nucleotide Excision Repair (NER) pathway. (mdpi.com)
- Here, we discuss current knowledge on chromatin remodelling with respect to the cellular response to DNA damage, with emphasis on the response to lesions resolved by nucleotide excision repair. (biomedcentral.com)
- Spontaneous reactions, such as hydrolysis, are the major sources of DNA damage. (hindawi.com)
- In addition, spontaneous hydrolysis of nucleotides induces non-instructive abasic sites. (biomedcentral.com)
- The goal of this study is to identify spontaneous DNA damage that is bypassed specifically and accurately by PolIV in vivo . (genetics.org)
- Major sources of DNA lesions are physical and chemical agents from the environment, intermediates of cellular metabolism, spontaneous chemical reactions of DNA, incorporation of foreign or damaged nucleotides, etc. [ 1 , 2 ]. (intechopen.com)
- NHEJ eliminates DNA double-strand breaks (DSBs) by direct ligation without the need for a homologous template, in contrast to homologous recombination. (curie.fr)
- NHEJ typically utilizes short homologous DNA sequences at the end of the broken DNA helix to hook and join the two ends together. (curie.fr)
- In this study, the functional relevance of this association was further investigated in the context to DNA repair. (biomedcentral.com)
- Leveraging cancer genomic data, we also find locally reduced SNV rates in promoters, coding sequence, and other functional elements. (springer.com)
- Here, we report that triple-helix formation itself is capable of promoting recombination and that this effect is dependent on a functional nucleotide excision repair (NER) pathway. (asm.org)
- Consequently, the DNA repair process must be constantly active so it can respond rapidly to any damage in the DNA structure. (bionity.com)
- Cellular genomic DNA constantly suffers from damage induced by various external genotoxic agents and endogenous metabolic materials. (biomedcentral.com)
- As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. (wikipedia.org)
- The integrity of DNA is constantly challenged by damaging agents and chemical modifications. (springer.com)
- DNA is a dynamic molecule that is constantly damaged and repaired. (intechopen.com)
- Amostras de DNA de nove CBCs de tecido armazenado em parafina e duas amostras de tumor gástrico de uma mesma peça cirúrgica, de tecido armazenado em parafina e congelado a fresco, foram avaliadas de forma pareada com o DNA de leucócito correspondente, para pesquisa de variantes somáticas. (bvsalud.org)
- Both nucleotide excision repair (NER) and the p53 tumor suppressor protein play crucial roles in the prevention of cells becoming cancerous. (aacrjournals.org)
- p53 heterozygosity had no influence on liver tumor incidences, in line with the results obtained from the short-term 2-AAF studies revealing no altered cellular response in p53 +/− or Xpa/p53 +/− mice. (aacrjournals.org)
- These studies demonstrate that E6 transformation of human tumor cells will influence both the frequency and types of chromosome aberrations observed after radiation exposure, and that these effects are related to the expression of potentially lethal damage. (smokershistory.com)
- We also highlight how these methods have provided key mechanistic insight into histone dynamics coupled to repair in mammals, raising new issues about the maintenance of chromatin integrity. (mdpi.com)
- Chromatin plasticity is particularly important during DNA repair as DNA damage occurs in an unscheduled manner and involves rearrangements of chromatin structure that prime chromatin for repair and help restore its integrity. (mdpi.com)
- Although it is generally believed that information stored is relatively safe and stable, the integrity of DNA is continuously challenged by numerous genotoxic agents and environmental stress. (biomedcentral.com)
- Assays that measure DNA repair capacity suggest that it can vary widely among individuals. (biomedcentral.com)
- yet, host cell reactivation assays and DNA array analysis indicate that the nucleotide excision repair (NER) pathway in the Hmgn1 −/− MEFs remains intact. (embopress.org)
- Herein we use a combination of in vitro and bacterial cell repair assays with single molecule fluorescence microscopy to demonstrate that both a C-terminal domain histidine residue and the 2-amino group of OG base are critical for MutY detection of OG:A sites. (bvsalud.org)
- The genotoxic potential of 19 diverse flavor and fragrance (F & F) agents was assessed in the Turkey Egg Genotoxicity Assay (TEGA) using 32P-nucleotide postlabeling (NPL) and comet assays to detect hepatic DNA adducts and strand breaks, respectively. (gta-us.org)
- For instance the serine/threonine kinase receptor associated protein (Strap) structurally contains one DNA binding OB fold as do the simple SSBs, while the TPP1 - protection of telomeres 1 (POT1) breast cancer 2, early onset (BRCA2) and the CST complex form complexes reminiscent of higher order SSBs. (biomedcentral.com)
- Successful repair requires MutY recognition of the OG:A mispair amidst highly abundant and structurally similar undamaged DNA base pairs. (bvsalud.org)
- Various DNA alterations can be caused by exposure to environmental and endogenous carcinogens. (medsci.org)
- Genotoxic exposure to tobacco carcinogens resulting in DNA damage is an important mechanism of oral squamous cell carcinoma (OSCC) etiology. (omicsonline.org)
- Genotoxic exposure to tobacco carcinogens and consequent adduct formation resulting in DNA damage is an important mechanism of OSCC etiology [ 3 ]. (omicsonline.org)
- These include DNA damage from UV radiation ( 54 ), chemical carcinogens ( 64 ), and photoreactive molecules such as psoralen ( 48 ). (asm.org)
- A variety of genotoxic carcinogens tested in the Chicken Egg Genotoxicity Assay (CEGA), which assesses liver DNA breaks and adducts, also interfered with fetal liver proliferation, differentiation and migration, leading to hepatocellular dysplasia and distortion of trabecular pattern. (gta-us.org)
- Furthermore, we found that Acr can greatly reduce the DNA repair capacity for damage induced by benzo[ a ]pyrene diol epoxide. (pnas.org)
- BPDE can react with nucleophylic groups in DNA, thereby forming DNA adducts, mainly consisting of BPDE-N2deoxyguanosin (BPDE-dG) (Cheng, S. C., Hilton, B. D., Roman, J. M. & Dipple, A. (1989) DNA adducts from carcinogenic and noncarcinogenic enantiomers of benzo[a]pyrene dihydrodiol epoxide Chem Res Toxicol 2, 334-40. (patentsencyclopedia.com)
- Although depletion of DNA-PKcs sensitized HeLa cells to UV radiation, it did not affect the ggNER efficiency of UV-induced cyclobutane pyrimidine dimers (CPD) damage. (biomedcentral.com)
- Therrien JP, Rouabhia M, Drobetsky EA, Drouin R. The multilayered organization of engineered human skin does not influence the formation of sunlight-induced cyclobutane pyrimidine dimers in cellular DNA. (medecinesciences.org)
- Such errors result in the accumulation of changes to RNA and protein sequences with age, and are tightly linked to cellular senescence and overall organ dysfunction. (pubmedcentralcanada.ca)
- This is due to the fluid nature of chromatin, a complex packaging system, in which DNA is wrapped around a protein core of four different histone dimers, forming the basic building blocks of chromatin called nucleosomes. (pubmedcentralcanada.ca)
- Using this method, we have investigated the role of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a member of the phosphatidylinositol 3-kinase-related protein kinases (PIKK) family, in the TCR pathway of UV-induced DNA damage. (biomedcentral.com)
- PMID:9407949 Yacoub A, Kelley MR, Deutsch WA (1998) The DNA repair activity of human redox/repair protein APE/Ref-1 is inactivated by phosphorylation. (curie.fr)
- PMID:11238996 Romero F, Multon MC, Ramos-Morales F, Dom-nguez A, Bernal JA, Pintor-Toro JA, Tortolero M (2001) Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase. (curie.fr)
- PMID:11955432 Ma Y, Pannicke U, Schwarz K, Lieber MR (2002) Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination. (curie.fr)
- We report that HMGN1, a nucleosome binding protein that destabilizes the higher‐order chromatin structure, modulates the repair rate of ultraviolet light (UV)‐induced DNA lesions in chromatin. (embopress.org)
- Another activity that may contribute to E6-associated carcinogenesis is its apparent inhibition of cellular differentiation. (smokershistory.com)
- Together these results suggest that Acr is a major etiological agent for CS-related lung cancer and that it contributes to lung carcinogenesis through two detrimental effects: DNA damage and inhibition of DNA repair. (pnas.org)
- With the increasing diversity and abundance of DNA damaging agents in the environment, it is very important for human health that active substances from medicinal and aromatic plants possess protective effects against genotoxic agents and under certain conditions could act as antimutagens. (intechopen.com)
- Here, we discuss the link between DNA damage, chromatin alterations and ageing, an interplay that explains how seemingly random DNA damage could manifest in predictable phenotypic changes that define ageing, changes that may ultimately be reversible. (pubmedcentralcanada.ca)
- It has been a long-standing question how DNA damage repair proceeds in a nuclear environment where DNA is packaged into chromatin. (mdpi.com)
- In particular, we discuss how NER factors and central players in chromatin dynamics such as histone modifiers, nucleosome remodeling factors, and histone chaperones function to mobilize histones during repair. (mdpi.com)
- In the cell nucleus, DNA is packaged into chromatin, a complex nucleoprotein structure whose basic unit is the nucleosome [ 1 ]. (mdpi.com)
- One of the key issues in the chromatin field is to understand how the information conveyed by chromatin is preserved while allowing all DNA metabolic activities ( i.e. (mdpi.com)
- For both damage signalling and repair, chromatin remodelling is most likely a prerequisite. (biomedcentral.com)
- In this review we summarize and discuss current knowledge on chromatin remodelling, with emphasis on one specific DNA repair process, nucleotide excision repair (NER). (biomedcentral.com)
- In contrast, we observe a reduction at chromatin loop anchors with increased damage load towards inactive compartments. (springer.com)
- By reducing the compaction of the higher‐order chromatin structure, HMGN1 facilitates access to UV‐damaged DNA sites and enhances the rate of DNA repair in chromatin. (embopress.org)
- The NER process is affected not only by direct contacts between histones and DNA but also by the structural features of the chromatin fiber. (embopress.org)
- and activities that reduce the compaction of the higher‐order chromatin structure, such as global histone acetylation ( Ramanathan and Smerdon, 1989 ), enhance the rate of UV repair. (embopress.org)
- The nucleosome core particle is composed of approximately 146 base pairs of DNA wrapped around an octamer of histone proteins comprising a (H3-H4) 2 tetramer flanked by two H2A-H2B dimers [ 2 ]. (mdpi.com)
- Unlike proteins and RNA , DNA usually lacks tertiary structure and therefore damage or disturbance does not occur at that level. (bionity.com)
- DNA is, however, supercoiled and wound around "packaging" proteins called histones (in eukaryotes), and both superstructures are vulnerable to the effects of DNA damage. (bionity.com)
- In these instances, single-stranded DNA binding proteins are essential for the sequestration and processing of single-stranded DNA. (biomedcentral.com)
- In order to bind single-stranded DNA, these proteins utilise a characteristic and evolutionary conserved single-stranded DNA-binding domain, the oligonucleotide/oligosaccharide-binding (OB)-fold. (biomedcentral.com)
- PMID:11972333 Christmann M, Tomicic MT, Kaina B (2002) Phosphorylation of mismatch repair proteins MSH2 and MSH6 affecting MutSalpha mismatch-binding activity. (curie.fr)
- The accrual of genomic defects can affect cellular function on many levels. (pubmedcentralcanada.ca)
- For more than a quarter of a century after that it was thought that only rare syndromes, such as XP, Cockayne syndrome (CS) and ataxia telangiectasia, were associated with DNA repair defects [ 4 ]. (medsci.org)
- In human cells, both normal metabolic activities and environmental factors such as UV light can cause DNA damage, resulting in as many as 1 million individual molecular lesions per cell per day. (bionity.com)
- Following metabolic activation, aristolochic acid reacts with DNA to form aristolactam (AL)-DNA adducts. (pnas.org)
- When the overhangs are perfectly compatible, NHEJ repairs the break accurately. (curie.fr)
- NHEJ involves binding of the KU heterodimer to double-stranded DNA ends, recruitment of DNA-PKcs (MRX complex in yeast), processing of ends, and recruitment of the DNA ligase IV (LIG4)-XRCC4 complex, which brings about ligation. (curie.fr)
- A stretch of nucleotides, containing the damaged nucleotide, is excised and replaced by a newly synthesized DNA strand. (aacrjournals.org)
- This strand-specific repair in a suitable restriction fragment is usually determined by alkaline gel electrophoresis followed by Southern blotting transfer and hybridization with an indirect end-labeled single-stranded probe. (biomedcentral.com)
- Besides double-strand breaks, other types of DNA damage have been shown to be recombinagenic, but in a non-site-specific way. (asm.org)
- PMID:11163244 Whitehouse CJ, Taylor RM, Thistlethwaite A, Zhang H, Karimi-Busheri F, Lasko DD, Weinfeld M, Caldecott KW (2001) XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair. (curie.fr)
- Additionally, BDHCA at 20 mg/egg, p-t-butyl-a-methylhydrocinnamic aldehyde (BMHCA) at 10 mg/egg, trans-2-hexenal (HEX) up to 10 mg/egg and maltol (MAL) up to 20 mg/egg produced DNA strand breaks. (gta-us.org)