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.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.N-Glycosyl Hydrolases: A class of enzymes involved in the hydrolysis of the N-glycosidic bond of nitrogen-linked sugars.Uracil-DNA Glycosidase: An enzyme that catalyzes the HYDROLYSIS of the N-glycosidic bond between sugar phosphate backbone and URACIL residue during DNA synthesis.DNA-Formamidopyrimidine Glycosylase: A DNA repair enzyme that is an N-glycosyl hydrolase with specificity for DNA-containing ring-opened N(7)-methylguanine residues.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.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 Repair Enzymes: Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.DNA Damage: Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.Thymine DNA Glycosylase: An enzyme that removes THYMINE and URACIL bases mispaired with GUANINE through hydrolysis of their N-glycosidic bond. These mispaired nucleotides generally occur through the hydrolytic DEAMINATION of 5-METHYLCYTOSINE to thymine.Deoxyribonuclease IV (Phage T4-Induced): An enzyme which catalyzes the endonucleolytic cleavage of phosphodiester bonds at purinic or apyrimidinic sites (AP-sites) to produce 5'-Phosphooligonucleotide end products. The enzyme prefers single-stranded DNA (ssDNA) and was formerly classified as EC Lyases: Enzymes that catalyze the cleavage of a carbon-oxygen bond by means other than hydrolysis or oxidation. EC 4.2.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.-.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).GuanineUracilHydantoins: Compounds based on imidazolidine dione. Some derivatives are ANTICONVULSANTS.Pentoxyl: 5-Hydroxymethyl-6-methyl- 2,4-(1H,3H)-pyrimidinedione. Uracil derivative used in combination with toxic antibiotics to lessen their toxicity; also to stimulate leukopoiesis and immunity. Synonyms: pentoksil; hydroxymethylmethyluracil.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.ThyminePeptide Nucleic Acids: DNA analogs containing neutral amide backbone linkages composed of aminoethyl glycine units instead of the usual phosphodiester linkage of deoxyribose groups. Peptide nucleic acids have high biological stability and higher affinity for complementary DNA or RNA sequences than analogous DNA oligomers.Base Pair Mismatch: The presence of an uncomplimentary base in double-stranded DNA caused by spontaneous deamination of cytosine or adenine, mismatching during homologous recombination, or errors in DNA replication. Multiple, sequential base pair mismatches lead to formation of heteroduplex DNA; (NUCLEIC ACID HETERODUPLEXES).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.Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids.Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.DNA Polymerase beta: A DNA repair enzyme that catalyzes DNA synthesis during base excision DNA repair. EC 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.Methanococcales: An order of anaerobic methanogens in the kingdom EURYARCHAEOTA. They are pseudosarcina, coccoid or sheathed rod-shaped and catabolize methyl groups. The cell wall is composed of protein. The order includes one family, METHANOCOCCACEAE. (From Bergey's Manual of Systemic Bacteriology, 1989)O(6)-Methylguanine-DNA Methyltransferase: An enzyme that transfers methyl groups from O(6)-methylguanine, and other methylated moieties of DNA, to a cysteine residue in itself, thus repairing alkylated DNA in a single-step reaction. EC 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.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.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.Adenine: A purine base and a fundamental unit of ADENINE NUCLEOTIDES.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.DNA Ligases: Poly(deoxyribonucleotide):poly(deoxyribonucleotide)ligases. Enzymes that catalyze the joining of preformed deoxyribonucleotides in phosphodiester linkage during genetic processes during repair of a single-stranded break in duplex DNA. The class includes both EC (ATP) and EC (NAD).Deoxyguanosine: A nucleoside consisting of the base guanine and the sugar deoxyribose.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.5-Methylcytosine: A methylated nucleotide base found in eukaryotic DNA. In ANIMALS, the DNA METHYLATION of CYTOSINE to form 5-methylcytosine is found primarily in the palindromic sequence CpG. In PLANTS, the methylated sequence is CpNpGp, where N can be any base.Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway.Korarchaeota: A kingdom in the domain ARCHAEA, comprising thermophilic organisms from terrestrial hot springs that are among the most primitive of all life forms. They have undergone comparatively little evolutionary change since the last common ancestor of all extant life.Methyl Methanesulfonate: An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.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.Polynucleotide 5'-Hydroxyl-Kinase: An enzyme that catalyzes the transfer of a phosphate group to the 5'-terminal hydroxyl groups of DNA and RNA. EC 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.Nucleic Acid Conformation: The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.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)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.Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).Guanosine: A purine nucleoside that has guanine linked by its N9 nitrogen to the C1 carbon of ribose. It is a component of ribonucleic acid and its nucleotides play important roles in metabolism. (From Dorland, 28th ed)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.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).Kinetics: The rate dynamics in chemical or physical systems.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.-.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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.DNA Adducts: The products of chemical reactions that result in the addition of extraneous chemical groups to 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.RNA: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.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.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.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)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.DNA Mismatch Repair: A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the BASE PAIR MISMATCH and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. (from Oxford Dictionary of Biochemistry and Molecular Biology, 2001)DNA Breaks, Double-Stranded: Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.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.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.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.Radiation Tolerance: The ability of some cells or tissues to survive lethal doses of IONIZING RADIATION. Tolerance depends on the species, cell type, and physical and chemical variables, including RADIATION-PROTECTIVE AGENTS and RADIATION-SENSITIZING AGENTS.DNA Methylation: Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.Deoxyadenosines: Adenosine molecules which can be substituted in any position, but are lacking one hydroxyl group in the ribose part of the molecule.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)Apurinic Acid: Hydrolysate of DNA in which purine bases have been removed.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.Dacarbazine: An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564)Methyltransferases: A subclass of enzymes of the transferase class that catalyze the transfer of a methyl group from one compound to another. (Dorland, 28th ed) EC 2.1.1.Thermodynamics: A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)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.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.Recombinational DNA Repair: Repair of DNA DAMAGE by exchange of DNA between matching sequences, usually between the allelic DNA (ALLELES) of sister chromatids.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.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.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.Rad52 DNA Repair and Recombination Protein: A DNA-binding protein that mediates DNA REPAIR of double strand breaks, and HOMOLOGOUS RECOMBINATION.Thermoproteaceae: A family of THERMOPROTEALES consisting of variable length rigid rods without septa. They grow either chemolithoautotrophically or by sulfur respiration. The four genera are: PYROBACULUM; THERMOPROTEUS; Caldivirga; and Thermocladium. (From Bergey's Manual of Systematic Bacteriology, 2d ed)DNA End-Joining Repair: The repair of DOUBLE-STRAND DNA BREAKS by rejoining the broken ends of DNA to each other directly.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Protein Structure, Secondary: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.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.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)DNA Replication: The process by which a DNA molecule is duplicated.Rad51 Recombinase: A Rec A recombinase found in eukaryotes. Rad51 is involved in DNA REPAIR of double-strand breaks.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.Bacterial Proteins: Proteins found in any species of bacterium.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.DNA Modification Methylases: Enzymes that are part of the restriction-modification systems. They are responsible for producing a species-characteristic methylation pattern, on either adenine or cytosine residues, in a specific short base sequence in the host cell's own DNA. This methylated sequence will occur many times in the host-cell DNA and remain intact for the lifetime of the cell. Any DNA from another species which gains entry into a living cell and lacks the characteristic methylation pattern will be recognized by the restriction endonucleases of similar specificity and destroyed by cleavage. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms.MutS Homolog 2 Protein: MutS homolog 2 protein is found throughout eukaryotes and is a homolog of the MUTS DNA MISMATCH-BINDING PROTEIN. It plays an essential role in meiotic RECOMBINATION and DNA REPAIR of mismatched NUCLEOTIDES.Furans: Compounds with a 5-membered ring of four carbons and an oxygen. They are aromatic heterocycles. The reduced form is tetrahydrofuran.DNA, Single-Stranded: A single chain of deoxyribonucleotides that occurs in some bacteria and viruses. It usually exists as a covalently closed circle.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.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.DNA, Mitochondrial: Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins.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.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.Aortic Aneurysm, Abdominal: An abnormal balloon- or sac-like dilatation in the wall of the ABDOMINAL AORTA which gives rise to the visceral, the parietal, and the terminal (iliac) branches below the aortic hiatus at the diaphragm.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Dose-Response Relationship, Radiation: The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation.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.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-Activated Protein Kinase: A serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.Cell Line, Tumor: A cell line derived from cultured tumor 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.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.Genomic Instability: An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.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.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.MutS DNA Mismatch-Binding Protein: A methyl-directed mismatch DNA REPAIR protein that has weak ATPASE activity. MutS was originally described in ESCHERICHIA COLI.Wound Healing: Restoration of integrity to traumatized tissue.Methylnitronitrosoguanidine: A nitrosoguanidine derivative with potent mutagenic and carcinogenic properties.Antigens, Nuclear: Immunologically detectable substances found in the CELL NUCLEUS.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.Blood Vessel Prosthesis Implantation: Surgical insertion of BLOOD VESSEL PROSTHESES to repair injured or diseased blood vessels.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.Formamides: A group of amides with the general formula of R-CONH2.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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.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.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.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Spiro Compounds: A group of compounds consisting in part of two rings sharing one atom (usually a carbon) in common.Homologous Recombination: An exchange of DNA between matching or similar sequences.Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.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.
MUTYH encodes DNA repair enzyme MYH glycosylase. During normal cellular activities, guanine sometimes becomes altered by oxygen ... MYH glycosylase fixes these mistakes by base excision repair, such that mutations do not accumulate in the DNA and lead to ... When MYH glycosylase does not function correctly, DNA errors may accrue to initiate tumorigenesis with a clinical presentation ...
DNA-3-methyladenine glycosylase is an enzyme that in yeast is encoded by the MAG1 gene. MAG1 is involved in protecting DNA ... It initiates base excision repair by removing damaged bases to create abasic sites that are subsequently repaired. "Entrez Gene ... MAG1: 3-methyl-adenine DNA glycosylase (Saccharomyces cerevisiae)". This article incorporates text from the United States ...
... (Alkylpurine glycosylase D) is an enzyme belonging to a family of DNA glycosylases that are involved in DNA repair. It was ... The enzyme specifically targets 7mG (methyl-guanine) in the DNA, and is, therefore, unique among DNA glycosylases. It can also ... "Structural insight into repair of alkylated DNA by a new superfamily of DNA glycosylases comprising HEAT-like repeats". Nucleic ... Vanderbilt University (29 October 2015). "New class of DNA repair enzyme discovered". ScienceDaily. Retrieved 1 November 2015. ...
"DNA glycosylase activities for thymine residues oxidized in the methyl group are functions of the hNEIL1 and hNTH1 enzymes in ... "Cloning and expression of the cDNA encoding the human homologue of the DNA repair enzyme, Escherichia coli endonuclease III". J ... "Distinct pattern of oxidative DNA damage and DNA repair in follicular thyroid tumours". J. Mol. Endocrinol. 48 (3): 193-202. ... Jiang Z, Hu J, Li X, Jiang Y, Zhou W, Lu D (2006). "Expression analyses of 27 DNA repair genes in astrocytoma by TaqMan low- ...
"Mammalian 5-formyluracil-DNA glycosylase. 2. Role of SMUG1 uracil-DNA glycosylase in repair of 5-formyluracil and other ... "Uracil-DNA glycosylase (UNG)-deficient mice reveal a primary role of the enzyme during DNA replication". Molecular Cell. 5 (6 ... "Mammalian 5-formyluracil-DNA glycosylase. 2. Role of SMUG1 uracil-DNA glycosylase in repair of 5-formyluracil and other ... Other DNA glycosylases linked to U removal are UNG, TDG and MBD4. Uracil-DNA repair is essential to protect against mutations. ...
DNA glycosylase/AP lyase enzymes are involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. These ... Formamidopyrimidine-DNA glycosylases (Fpg, MutM) is a trifunctional DNA base excision repair enzyme that removes a wide range ... enzymes have both DNA glycosylase activity (EC) and AP lyase activity (EC). Examples include formamidopyrimidine-DNA ... "Crystal structure of a repair enzyme of oxidatively damaged DNA, MutM (Fpg), from an extreme thermophile, Thermus thermophilus ...
... is a DNA-binding domain found in DNA glycosylase/AP lyase enzymes, which are involved in base excision repair of DNA damaged by ... Formamidopyrimidine-DNA glycosylases (Fpg, MutM) is a trifunctional DNA base excision repair enzyme that removes a wide range ... Most damage to bases in DNA is repaired by the base excision repair pathway. These enzymes are primarily from bacteria, and ... "Crystal structure of a repair enzyme of oxidatively damaged DNA, MutM (Fpg), from an extreme thermophile, Thermus thermophilus ...
Dou H, Mitra S, Hazra TK (Dec 2003). "Repair of oxidized bases in DNA bubble structures by human DNA glycosylases NEIL1 and ... crystallization and preliminary crystallographic analysis of a novel human DNA-repair enzyme that recognizes oxidative DNA ... If DNA repair is deficient, DNA damage tends to accumulate. Such excess DNA damage may increase mutational errors during DNA ... This was the most frequent DNA repair deficiency found among the 8 DNA repair genes tested. NEIL1 was also one of six DNA ...
Dou H, Mitra S, Hazra TK (2004). "Repair of oxidized bases in DNA bubble structures by human DNA glycosylases NEIL1 and NEIL2 ... Endonuclease VIII-like 2 is an enzyme that in humans is encoded by the NEIL2 gene. NEIL2 belongs to a class of DNA glycosylases ... APE-independent repair of oxidized bases in DNA: Evidence for a repair complex in human cells". DNA Repair (Amst.). 5 (12): ... "A novel human DNA glycosylase that removes oxidative DNA damage and is homologous to Escherichia coli endonuclease VIII". DNA ...
This can lead to a point mutation if not repaired by the DNA repair enzymes such as uracil glycosylase, which cleaves a uracil ... Cytosine can also be methylated into 5-methylcytosine by an enzyme called DNA methyltransferase or be methylated and ... Cytosine can be found as part of DNA, as part of RNA, or as a part of a nucleotide. As cytidine triphosphate (CTP), it can act ... Cytosine has not been found in meteorites, which suggests the first strands of RNA and DNA had to look elsewhere to obtain this ...
To ensure genetic integrity of the DNA, enzymes need to repair any damage. There are many types of DNA repair. Base excision ... DNA glycosylases interact with DNA, flipping bases to determine a mismatch. An example of base excision repair occurs when a ... DNA repair Base excision repair DNA replication RNA transcription DNA methylation DNA methyltransferase Genetic recombination ... various DNA repair mechanisms, RNA transcription and DNA replication. DNA can have mutations that cause a base in the DNA ...
... endonuclease XPG stimulates the activity of base excision repair enzyme thymine glycol DNA glycosylase". Nucleic Acids Res. 27 ... A DNA repair-deficiency disorder is a medical condition due to reduced functionality of DNA repair. DNA repair defects can ... Bernstein C, Bernstein H, Payne CM, Garewal H. DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways: ... "The human Werner syndrome protein stimulates repair of oxidative DNA base damage by the DNA glycosylase NEIL1". J. Biol. Chem. ...
Base excision repair (BER) repairs damage to a single nitrogenous base by deploying enzymes called glycosylases. These enzymes ... of some DNA repair enzymes Human DNA repair diseases DNA repair special interest group DNA Repair DNA Damage and DNA Repair ... Reduced expression of DNA repair genes causes deficient DNA repair. When DNA repair is deficient DNA damages remain in cells at ... Deficiencies in DNA repair enzymes are occasionally caused by a newly arising somatic mutation in a DNA repair gene, but are ...
Repair of DNA crosslinks[edit]. Crosslinked DNA is repaired in cells by a combination of enzymes and other factors from the ... as demonstrated in human alkyladenine DNA glycosylase (AAG) and E. coli 3-methyladenine DNA glycosylase II (AlkA).[19] in vitro ... intrastrand DNA crosslinks, interstrand DNA crosslinks, and DNA-protein crosslinks.[4] When cisplatin generates DNA crosslinks ... DNA repair pathways can result in the formation of tumor cells. Cancer treatments have been engineered using DNA cross-linking ...
... of Biochemistry and Molecular Biology at Harvard University Discovered two enzymes involved in the repair of damaged DNA: ... Formamidopyrimidine DNA Glycosylase, which removes damaged 7-methylguanine from DNA (1979). DNA cyclase, which recloses ... "Release of 7-methylguanine residues whose imidazole rings have been opened from damaged DNA by a DNA glycosylase from ... Chetsanga, C.J.; Grigorian, C. (1985). "In situ enzymatic reclosure of opened imidazole rings of purines in DNA damaged by ...
This leaves an abasic site that is repaired by AP endonucleases and polymerase, like with uracil-DNA glycosylase. Deamination ... In DNA, this reaction, if detected prior to passage of the replication fork, can be corrected by the enzyme thymine-DNA ... by uracil-DNA glycosylase, generating an abasic (AP) site. The resulting abasic site is then recognised by enzymes (AP ... Correction of this mutation involves the use of alkyladenine glycosylase (Aag) during base excision repair. Deamination of ...
... of AML-ETO that could induce leukemogenesis include downregulation of the DNA repair enzyme 8-oxoguanine DNA glycosylase (OGG1 ... RUNX1 can bind DNA as a monomer, but its DNA binding affinity is enhanced by 10 fold if it heterodimerises with the core ... The runt domain of RUNX1 binds to the core consensus sequence TGTGGNNN (where NNN can represent either TTT or TCA). DNA ... As a transcription factor (TF), its DNA binding ability is encoded by the runt domain (residues 50 - 177), which is homologous ...
This recombination requires uracil-DNA glycosylase, an enzyme that removes uracil from the DNA backbone and initiates base ... DNA damage (naturally occurring) DNA repair Yeast PomBase Wilhelm; et al. (2008). "Dynamic repertoire of a eukaryotic ... This finding suggests that meiosis, and particularly meiotic recombination, may be an adaptation for repairing DNA damage. ... DNA replication in yeast has been increasingly studied by many researchers. Further understanding of DNA replication, gene ...
The uracil bases are removed by the repair enzyme, uracil-DNA glycosylase. Error-prone DNA polymerases are then recruited to ... A key feature is its critical dependence on the gap-filling error prone DNA repair synthesis properties of DNA polymerase-eta ... Steele, E.J.; Lindley, R.A. (2017). "RNA DNA Hybrids and SHM". DNA Repair. April 15, 2017. Lindley, R.A. (2013). "The ... Editing (A-to-I) of the DNA moiety at RNA:DNA hybrids in vivo cannot explain the A>>T strand bias because such direct DNA ...
Uracil-DNA glycosylases are DNA repair enzymes that excise uracil residues from DNA by cleaving the N-glycosydic bond, ... Lindahl, T. (1986). "DNA Glycosylases in DNA Repair". Mechanisms of DNA Damage and Repair: 335-340. doi:10.1007/978-1-4615-9462 ... This entry represents various uracil-DNA glycosylases and related DNA glycosylases (EC), such as uracil-DNA glycosylase, ... AlkA refers to 3-methyladenine DNA glycosylase II. DNA glycosylases involved in base excision repair (BER) may be associated ...
Park J, Chen L, Tockman MS, Elahi A, Lazarus P (2004). "The human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) DNA repair enzyme ... 8-Oxoguanine glycosylase also known as OGG1 is a DNA glycosylase enzyme that, in humans, is encoded by the OGG1 gene. It is ... "Role of XRCC1 in the coordination and stimulation of oxidative DNA damage repair initiated by the DNA glycosylase hOGG1". J. ... "DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers". ...
"Molecular cloning of human uracil-DNA glycosylase, a highly conserved DNA repair enzyme". The EMBO Journal. 8 (10): 3121-5. PMC ... "Human immunodeficiency virus type 1 Vpr protein binds to the uracil DNA glycosylase DNA repair enzyme". Journal of Virology. 70 ... Uracil N-glycosylase was also used in a study to detect evidence of ongoing low-level metabolic activity and DNA repair in ... Uracil-DNA glycosylase, also known as UNG or UDG, is an enzyme. The human gene is well researched and orthologs exist ...
Lindahl T (1982). "DNA repair enzymes". Annu. Rev. Biochem. 51: 61-87. doi:10.1146/annurev.bi.51.070182.000425. PMID 6287922. ... 2002). "Association of CBP/p300 acetylase and thymine DNA glycosylase links DNA repair and transcription". Mol. Cell. 9 (2): ... 2001). "The DNA glycosylase T:G mismatch-specific thymine DNA glycosylase represses thyroid transcription factor-1-activated ... The protein encoded by this gene belongs to the TDG/mug DNA glycosylase family. Thymine-DNA glycosylase (TDG) removes thymine ...
... (FPG) is a base excision repair enzyme which recognizes and removes a wide range of ... "Release of 7-methylguanine residues whose imidazole rings have been opened from damaged DNA by a DNA glycosylase from ... "Crystal structure of the Lactococcus lactis formamidopyrimidine-DNA glycosylase bound to an abasic site analogue-containing DNA ... oxidized purines from correspondingly damaged DNA. It was discovered by Zimbabwean scientist Christopher J. Chetsanga in 1975. ...
"Expression of the DNA repair enzyme, N-methylpurine-DNA glycosylase (MPG) in astrocytic tumors". Anticancer Research. 23 (2B): ... DNA-3-methyladenine glycosylase also known as 3-alkyladenine DNA glycosylase (AAG) or N-methylpurine DNA glycosylase (MPG) is ... Alkyladenine DNA glycosylase is a specific type of DNA glycosylase. This subfamily of monofunctional glycosylases is involved ... "Methylated DNA-binding domain 1 and methylpurine-DNA glycosylase link transcriptional repression and DNA repair in chromatin". ...
8-Oxoguanine glycosylase also known as OGG1 is a DNA glycosylase enzyme that, in humans, is encoded by the OGG1 gene. It is involved in base excision repair. It is found in bacterial, archaeal and eukaryotic species. OGG1 is the primary enzyme responsible for the excision of 8-oxoguanine (8-oxoG), a mutagenic base byproduct that occurs as a result of exposure to reactive oxygen species (ROS). OGG1 is a bifunctional glycosylase, as it is able to both cleave the glycosidic bond of the mutagenic lesion and cause a strand break in the DNA backbone. Alternative splicing of the C-terminal region of this gene classifies splice variants into two major groups, type 1 and type 2, depending on the last exon of the sequence. Type 1 alternative splice variants end with exon 7 and type 2 end with exon 8. One set of spliced forms are designated 1a, 1b, 2a to 2e. All variants have the ...
Dr. Tomas Lindahl is noted for his contributions to the comprehension of DNA repair at the molecular level in bacterial and mammalian cells. He was the first to isolate a mammalian DNA ligase and to describe a totally unanticipated novel group of DNA glycosylases as mediators of DNA excision repair. He has also discovered a unique class of enzymes in mammalian cells, namely the methyltransferases, which mediate the adaptive response to alkylation of DNA and has shown that the expression of these enzymes is regulated by the ada gene. More recently he has elucidated the molecular defect in Blooms syndrome [sic] to be the lack of ...
The sperm and egg fuse in the process of fertilization to form a fertilized egg, or zygote.[12] This undergoes a period of divisions to form a ball or sheet of similar cells called a blastula or blastoderm. These cell divisions are usually rapid with no growth so the daughter cells are half the size of the mother cell and the whole embryo stays about the same size. They are called cleavage divisions. Mouse epiblast primordial germ cells (see Figure: "The initial stages of human embryogenesis") undergo extensive epigenetic reprogramming.[13] This process involves genome-wide DNA demethylation, chromatin reorganization and epigenetic imprint erasure leading to totipotency.[13] DNA demethylation is carried out by a process that utilizes the DNA base excision repair pathway.[14] Morphogenetic movements convert the cell mass into ...
... je jedna od četiri nukleobaza RNK, koja zamenjuje timin koji se nalazi u DNK. Kao i timin, uracil može da formira bazni par sa adeninom pomoću dve vodonične veze, ali mu nedostaje metil grupa koja postoji u timinu. Uracil će, za razliku od timina, lakše da se degeneriše u citozin. Uracil se vrlo retko može naći u DNK. ...
Endogeensed retroviirused (ERV-d) on genoomis esinevad endogeensed viraalsed elemendid, mis meenutavad või mida saab tuletada retroviiruste DNA-st. Neid esineb rohkelt lõugsuuste genoomides ja nad moodustavad inimgenoomist 4,9%.[1] ERV-d on teatud tüüpi genoomi piires liikumisvõimeliste ehk genoomis ümberpaiknemis võimeliste geenide - transposoonide - alamklass. Neil on oluline roll geenide ekspressioonil ja regulatsioonil.[2][3]. ...
B5-vitamiini lisatarbimine on kindlasti vajalik pikaaegse defitsiidi tunnuste ilmnemisel. Neil, kes tarbivad kestvalt ülemäära palju alkoholi ja kohvi, on selle vitamiini lisatarbimine õigustatud. Selle oskuslik ja adekvaatne manustamine võib ravi ühe komponendina olla efektiivne ka alkoholismi, depressiooni, tuberkuloosi, aneemia ja muude haiguste puhul.. Pantoteenhapet peaks kindlasti manustama koos tiamiini, niatsiini, B6-vitamiini, C-vitamiini, foolhappe, biotiini ja kaltsiumiga.. ...
DNA excision repair protein ERCC-1 is a protein that in humans is encoded by the ERCC1 gene. Together with ERCC4, ERCC1 forms the ERCC1-XPF enzyme complex that participates in DNA repair and DNA recombination. Many aspects of these two gene products are described together here because they are partners during DNA repair. The ERCC1-XPF nuclease is an essential activity in the pathway of DNA nucleotide excision repair (NER). The ERCC1-XPF nuclease also functions in pathways to repair double-strand breaks in DNA, and in the ...
The XPA protein acts during NER as a scaffold for assembly of other DNA repair proteins at sites of DNA damage to ensure appropriate excision of the damage.[12]. The XPB (ERCC3) protein is employed in unwinding the DNA double helix after DNA damage is initially recognized. Mutations in the XPB(ERCC3) gene can lead to XP or XP combined with Cockayne syndrome.[13]. The XPC protein forms a complex with RAD23B protein to form the initial damage recognition factor in global genomic nucleotide excision repair (GG-NER).[14] This complex recognizes a wide variety of damages that thermodynamically destabilize DNA duplexes. The XPD (ERCC2) protein, in combination with the XPB helicase-containing ...
Crosslinked DNA is repaired in cells by a combination of enzymes and other factors from the nucleotide excision repair (NER) pathway, homologous recombination, and the base excision repair (BER) pathway. To repair interstrand crosslinks in eukaryotes, a 3' flap endonuclease from the NER, XPF-ERCC1, is recruited to the crosslinked DNA, where it assists in 'unhooking' the DNA by cleaving the 3' strand at the crosslink site. The 5' strand is then cleaved, either by XPF-ERCC1 or another endonuclease, forming a double-strand break (DSB), which can then be repaired by the homologous recombination pathway.[17] DNA crosslinks ...
Flap endonuclease 1 is an enzyme that in humans is encoded by the FEN1 gene. The protein encoded by this gene removes 5' overhanging "flaps" (or short sections of single stranded DNA that "hang off" because their nucleotide bases are prevented from binding to their complementary base pair-despite any base pairing downstream) in DNA repair and processes the 5' ends of Okazaki fragments in lagging strand DNA synthesis. Direct physical interaction between this protein and AP endonuclease 1 during long-patch base excision repair provides coordinated loading of the proteins onto the substrate, thus passing the substrate from one enzyme to another. The protein is a member of the XPG/RAD2 endonuclease family and is one of ten proteins essential for cell-free ...
DNA damage (or RNA damage in the case of some virus genomes) appears to be a fundamental problem for life. As noted by Haynes,[14] the subunits of DNA are not endowed with any peculiar kind of quantum mechanical stability, and thus DNA is vulnerable to all the "chemical horrors" that might befall any such molecule in a warm aqueous medium. These chemical horrors are DNA damages that include various types of modification of the DNA bases, single- and double-strand breaks, and inter-strand cross-links (see DNA damage (naturally occurring). DNA damages are distinct from mutations although both are errors in the ...
VSR recognises a TG mismatched base pair, generated after spontaneous deamination of methylated cytosines, and it creates a nick on a single strand by cleaving the phosphate backbone on the 5' side of the thymine.[1] Then DNA Polymerase I removes the T and some nucletides on the 3' strand and then resynthesises the patch.[2]. Additionally, GT mismatches can lead to C-to-T transition mutations if not repaired. VSR repairs the mismatches in favour of the G-containing strand. In Escherichia coli, this endonuclease nicks double-stranded DNA within the sequence CT(AT)GN or NT(AT)GG next to the thymidine residue, which is mismatched to 2'-deoxyguanosine.[3] The incision is mismatch-dependent and strand specific.. ...
... , or nucleotide flipping, is a mechanism in which a single nucleotide base, or nucleobase, is rotated outside the nucleic acid double helix. This occurs when a nucleic acid-processing enzyme needs access to the base to perform work on it, such as its excision for replacement with another base during DNA repair. It was first observed in 1994 using X-ray crystallography in a methyltransferase enzyme catalyzing methylation of a cytosine base in DNA. Since then, it has been shown to be used by different enzymes in many biological processes such as DNA methylation, various DNA repair mechanisms, and DNA replication. It can also occur in RNA double helices or in the ...
Involvement of two endonuclease III homologs in the base excision repair pathway for the processing of DNA alkylation damage in ... DNA Glycosylases * DNA Repair * DNA Repair Enzymes * DNA Replication * DNA, Fungal * DNA-(Apurinic or Apyrimidinic Site) Lyase ... DNA base excision repair (BER) is initiated by DNA glycosylases that recognize and remove damaged bases. The phosphate backbone ... Involvement of two endonuclease III homologs in the base excision repair pathway for the processing of DNA alkylation damage in ...
It is generally believed that the repair of AP ... One of the most frequent lesions formed in cellular DNA are ... Enzymes Restriction enzymes and uracil DNA glycosylase were from New England Biolabs and E.coli MutY was from Trevigen. ... DNA Glycosylases / genetics, metabolism, physiology*. DNA Mutational Analysis. DNA Repair*. DNA-(Apurinic or Apyrimidinic Site ... The AP lyase activity is associated with bifunctional DNA glycosylases that are major repair enzymes existing in all organisms ...
Properties of DNA Repair Enzymes Enzyme Substrate Cleavage site Termini created from cleavage 5 terminus 3 terminus APE 1 AP ... NEB carries an array of reliable DNA repair enzymes for use in multiple applications. ... DNA Repair Glycosylases on Various Damaged Bases. Double-stranded DNA Oligos (34-mers). ... Properties of DNA Repair Enzymes Properties of DNA Repair Enzymes. NEB carries an array of reliable DNA repair enzymes for use ...
... in Uracil-DNA N-glycosylases (UNGs) undergoes significant conformational changes upon substrate interaction. Previous s.. ... Uracil-DNA N-glycosylase (UNG) is a DNA repair enzyme involved in the base excision repair pathway (BER) for removal of uracil ... Cold adaptation of enzymes; DNA repair; Uracil-DNA N-glycosylase; Kinetics; Differential scanning calorimetry. ... Electrostatic interactions play an essential role in DNA repair and cold-adaptation of uracil DNA glycosylase.J Mol Model 14: ...
Lindahl T (1982). "DNA repair enzymes". Annu. Rev. Biochem. 51: 61-87. doi:10.1146/annurev.bi.51.070182.000425. PMID 6287922. ... 2002). "Association of CBP/p300 acetylase and thymine DNA glycosylase links DNA repair and transcription". Mol. Cell. 9 (2): ... 2001). "The DNA glycosylase T:G mismatch-specific thymine DNA glycosylase represses thyroid transcription factor-1-activated ... The protein encoded by this gene belongs to the TDG/mug DNA glycosylase family. Thymine-DNA glycosylase (TDG) removes thymine ...
Vpr drives the repair enzyme uracil DNA glycosylase (UNG2) towards degradation. UNG2 has a major role in "Base excision repair ... hUNG2 is the major repair enzyme for removal of uracil from U:A matches, U:G mismatches, and U in single-stranded DNA, with ... Ahn J, Vu T, Novince Z, Guerrero-Santoro J, Rapic-Otrin V, Gronenborn AM (2010) HIV-1 Vpr loads uracil DNA glycosylase-2 onto ... Krokan HE, Drabløs F, Slupphaug G (2002) Uracil in DNA: occurrence, consequences and repair. Oncogene 21:8935-8948CrossRef ...
Uracil-DNA glycosylases are DNA repair enzymes that excise uracil residues from DNA by cleaving the N-glycosylic bond, ... This entry represents various uracil-DNA glycosylases and related DNA glycosylases (EC:3.2.2), such as uracil-DNA glycosylase [ ... Thermostable uracil-DNA glycosylase from Thermotoga maritima a member of a novel class of DNA repair enzymes.. Curr. Biol. 9 ... Molecular cloning of human uracil-DNA glycosylase, a highly conserved DNA repair enzyme.. EMBO J. 8 3121-5 1989 ...
Excises 7,8-dihydro-8-oxoguanine and 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine (FAPY) from damaged DNA. Has a beta- ... lyase activity that nicks DNA 3 to the lesion. ... DNA repair enzyme that incises DNA at 8-oxoG residues. ... DNA repair enzyme that incises DNA at 8-oxoG residues. Excises 7,8-dihydro-8-oxoguanine and 2,6-diamino-4-hydroxy-5-N- ... damaged DNA binding Source: InterPro. *oxidized purine nucleobase lesion DNA N-glycosylase activity Source: SGD ,p>Inferred ...
Using DNA glycosylases, damaged bases can be removed. The abasic sites are then cleaved by one of two classes of enzymes. One ... Structural Biochemistry/DNA Repair/Polynucleotide kinase/phosphatase in DNA strand break repair. From Wikibooks, open books for ... In addition to this, PNKP also helps in other DNA repair pathways through interactions with other DNA repair proteins such as ... XRcc1 and XRCC4 are important scaffolding proteins that repair DNA SSBs and DSBs. Aprataxin and APLF are DNA repair factors ...
... in DNA are temporary because they are immediately corrected by a set of processes that are collectively called DNA repair. Of ... but also mechanisms for repairing the many accidental lesions that occur continually in DNA. Most such spontaneous changes ... only a few accumulate as mutations in the DNA sequence. We now know that fewer than one in 1000 accidental base changes in DNA ... the rest are eliminated with remarkable efficiency by DNA repair. ... the thousands of random changes created every day in the DNA of ...
MUTYH encodes DNA repair enzyme MYH glycosylase. During normal cellular activities, guanine sometimes becomes altered by oxygen ... MYH glycosylase fixes these mistakes by base excision repair, such that mutations do not accumulate in the DNA and lead to ... When MYH glycosylase does not function correctly, DNA errors may accrue to initiate tumorigenesis with a clinical presentation ...
... this was found to be a G/T mismatch repair DNA glycosylase (13). MBD4, a human homolog of the chicken enzyme, also has 5- ... methylcytosine DNA glycosylase activity (14). At least in vitro, these G/T mismatch repair DNA glycosylases appear to be ... The DNA 5-methylcytosine glycosylase activity of ROS1 is 10-15 times higher than its G:T mismatch repair activity (Fig. 3 A and ... Repair reactions catalyzed by all bifunctional DNA glycosylase/lyases proceed through a transient imino intermediate (Schiff ...
MBD4 is sumoylated in vivo in a DNA damage-specific manner Title: Modification of the base excision repair enzyme MBD4 by the ... MBD4 methyl-CpG binding domain 4, DNA glycosylase [Homo sapiens] MBD4 methyl-CpG binding domain 4, DNA glycosylase [Homo ... methylated DNA and in protein interactions and a C-terminal mismatch-specific glycosylase domain that is involved in DNA repair ... 3,N(4)-ethenocytosine glycosylase. G/5-fluorouracil mismatch glycosylase with biphasic kinetics. G/T mismatch glycosylase. G/U ...
Using gene-targeted cell lines defective in one or both of the two mammalian uracil-DNA glycosylase repair enzymes, we were ... In vitro DNA repair assays. In vitro, the Ung and Smug1 uracil-DNA glycosylases efficiently excise uracil from U:A base pairs ... Uracil-DNA glycosylase (UNG)-deficient mice reveal a primary role of the enzyme during DNA replication. Mol Cell 2000; 5: 1059- ... Base excision repair enzyme MED1 mediates DNA damage response to antitumor drugs and is associated with mismatch repair system ...
... principle repair pathways. The first enzyme in the BER process is glycosylase. Uracil DNA glycosylase (UDG) is one of 11 ... DNA Binding. Uracil-DNA glycosylase is lesion-specific (as the name suggests) for in DNA. For DNA to be bound by UDG, it must ... Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil-DNA glycosylase of DNA. The ... Uracil-DNA Glycosylase. Rei Mitsuyama 15 and Holden Richards 15 Contents:. I. Introduction II. General Structure III. DNA ...
... repair pathways to maintain the integrity of their genetic information, including DNA base excision repair (BER) ... Mechanisms of DNA base excision repair. A DNA glycosylase removes a damaged base. The enzyme apurinic/apyrimidic endonuclease 1 ... recognizes DNA damage caused by exogenous molecules and oxidative stress and signals for DNA repair. If the DNA damage is ... Inhibitors of the DNA base excision repair enzymes are being investigated as potential treatments for cancer and severe ...
Dna array explanation free. What is Dna array? Meaning of Dna array medical term. What does Dna array mean? ... Looking for online definition of Dna array in the Medical Dictionary? ... DNA glycosylases. enzymes involved in the excision-repair mechanisms for DNA.. heteroduplex DNA. duplex DNA with each strand ... DNA ligase. an enzyme that seals nicks in the DNA helix, joins Okazaki fragments together during DNA replication and is ...
DNA gyrase explanation free. What is DNA gyrase? Meaning of DNA gyrase medical term. What does DNA gyrase mean? ... Looking for online definition of DNA gyrase in the Medical Dictionary? ... DNA glycosylases. enzymes involved in the excision-repair mechanisms for DNA.. heteroduplex DNA. duplex DNA with each strand ... Related to DNA gyrase: Topoisomerase, Quinolones. DNA gyrase. (ji´rās) a type II DNA topoisomerase.. DNA gyrase. an enzyme that ...
Importantly, this method can be extended to simultaneously detect other types of DNA repair enzymes by just using specific ... uracil DNA glycosylase (UDG) and thymine DNA glycosylase (TDG) as negative controls. BSA is not a DNA glycosylase, and it ... DNA glycosylases are involved in the base excision repair pathway, and all mammals express multiple DNA glycosylases to ... Recent research reveals that human 8-oxoguanine DNA glycosylase (hOGG1)12,13 and human alkyladenine DNA glycosylase (hAAG)14 ...
Histone deacetylase SIRT1 modulates and deacetylates DNA base excision repair enzyme thymine DNA glycosylase Biochem J (October ... Cultures of arrested cells, via contact inhibition or DNA damage, exhibited decreased Rb phosphorylation and increased Rb ...
There are two general classes of DNA repair; the direct reversal of the chemical process generating the damage and the ... The mechanism requires a family of enzymes called glycosylases. The enzymes remove the damaged base forming an AP site which is ... Sunderland (MA): Sinauer Associates: DNA Repair.. *Eker, A.P. et al. 2009. DNA repair in mammalian cells: Direct DNA damage ... The direct reversal DNA repair mechanism. Direct reversal of DNA damage is a mechanism of repair that does not require a ...
The hyperthermophilic and radioresistant euryarchaeon Thermococcus gammatoleransencodes an archaeal GO DNA... ... is a major lesion found in DNA that arises from guanine oxidation. ... Thayer MM, Ahern H, Xing D, Cunningham RP, Tainer JA (1995) Novel DNA binding motifs in the DNA repair enzyme endonuclease III ... Cloning of a yeast 8-oxoguanine DNA glycosylase reveals the existence of a base-excision DNA-repair protein superfamily. Curr ...
Repair of formamidopyrimidines in DNA involves different glycosylases: Role of the OGG1, NTH1, and NEIL1 enzymes. J. Biol. Chem ... ROS-induced DNA peroxidation interrupts gene transcription and causes gene mutations. The principal oxidative DNA damage (ODD) ... The levels and activities of these enzymes are due to the change under abnormal conditions. The levels of these enzymes could ... ganglia when apurinic/apyrimidinic endonuclease/redox factor-1 that is involved in DNA base excision repair of oxidative DNA ...
This enzyme binds to sites of oxidative DNA damage and initiates DNA base excision repair. Visnes et al. developed a small- ... DNA binding as an anti-inflammatory. Mice that lack the gene encoding 8-oxoguanine DNA glycosylase 1 (OGG1) show resistance to ... A small-molecule OGG1 glycosylase inhibitor suppresses inflammation by targeting oxidative DNA repair. ... A small-molecule OGG1 glycosylase inhibitor suppresses inflammation by targeting oxidative DNA repair. ...
The domains of mammalian base excision repair enzyme N-methylpurine-DNA glycosylase. Interaction, conformational change, and ... A high-throughput RNA interference screen for DNA repair determinants of PARP inhibitor sensitivity. DNA Repair (Amst) 2008;7: ... Three-dimensional structure of the human DNA-PKcs/Ku70/Ku80 complex assembled on DNA and its implications for DNA DSB repair. ... Analysis of DNA repair and chromatin assembly in vitro using immobilized damaged DNA substrates. Methods Mol Biol 2006;314:477- ...
  • The protein encoded by this gene belongs to the TDG/mug DNA glycosylase family. (wikipedia.org)
  • Thymine-DNA glycosylase has been shown to interact with: CREB-binding protein, Estrogen receptor alpha, Promyelocytic leukemia protein, SUMO3, and Small ubiquitin-related modifier 1. (wikipedia.org)
  • Genetic evidence suggested that the DNA glycosylase domain-containing protein ROS1 of Arabidopsis is a putative DNA demethylase, because loss-of-function ros1 mutations cause DNA hypermethylation and enhance transcriptional gene silencing. (pnas.org)
  • In addition, the methyl CpG-binding protein MBD2 was reported to be a DNA demethylase that hydrolyzes 5-methylcytosine to cytosine and methanol ( 19 ). (pnas.org)
  • Mutations in the DNA glycosylase domain-containing protein ROS1 in Arabidopsis cause DNA hypermethylation and transcriptional gene silencing (TGS) of the RD29A-LUC (firefly luciferase driven by the RD29A promoter) transgene and the endogenous RD29A gene ( 22 ). (pnas.org)
  • This protein contains an MBD domain at the N-terminus that functions both in binding to methylated DNA and in protein interactions and a C-terminal mismatch-specific glycosylase domain that is involved in DNA repair. (nih.gov)
  • In short patch‐base excision repair (SP‐BER), DNA polymerase β (Pol β) inserts the appropriate deoxynucleotide and cleaves the deoxyribose phosphate (dRP) group before DNA ligase III (Lig III) and X‐ray cross‐complimenting protein 1 (XRCC1) resolve the structure. (els.net)
  • Fishel M and Kelley M (2007) The DNA base excision repair protein Ape1/Ref‐1 as a therapeutic and chemopreventive target. (els.net)
  • Similarly to other biochemical modifications such as protein phosphorylation and acetylation, DNA methylation is also reversible. (pnas.org)
  • A 5-meC DNA glycosylase activity was first identified in chicken embryos ( 15 ) and found to copurify with a protein homologous to human thymine DNA glycosylase (TDG) ( 16 , 17 ). (pnas.org)
  • It was latter reported that methyl-CpG binding protein (MBD) 4, another human DNA glycosylase with no sequence similarity to TDG, also has 5-meC DNA glycosylase activity ( 18 ). (pnas.org)
  • Small molecule inhibitors of DNA repair are emerging as potent and selective anticancer therapies, but the sheer magnitude of the protein networks involved in DNA repair processes poses obstacles to discovery of effective candidate drugs. (aacrjournals.org)
  • Supporting the concept that these ligands have therapeutic potential, we show that one selected peptide specifically binds and noncompetitively inactivates DNA-PKcs, a protein kinase critical in double-strand DNA break repair. (aacrjournals.org)
  • Unbound phage were collected, and positive selection was subsequently carried out on 1 mg of DNA-coated magnetic beads prebound to 100 μg of nuclear protein (37°C for 30 minutes) and incubated in PBS for 30 minutes at RT. (aacrjournals.org)
  • Only two protein side chains (Glu-6 and Tyr-253) are within hydrogen-bonding contact with either damaged base, and mutating these residues did not markedly affect the glycosylase activity. (rcsb.org)
  • Nucleotide mimicry in the crystal structure of the uracil-DNA glycosylase-uracil glycosylase inhibitor protein comlex", Nature Structural Biology, vol. 2: p. 752-757, (1995). (freepatentsonline.com)
  • This gene encodes the catalytic subunit of the DNA-dependent protein kinase (DNA-PK). (antikoerper-online.de)
  • It functions with the Ku70/Ku80 heterodimer protein in DNA double strand break repair and recombination. (antikoerper-online.de)
  • OGG1 protein is the main enzyme accountable for the excision of 7,8-dihydro-8-oxoguanine (8-oxoG), a mutagenic base byproduct which arises as a result of exposure to reactive oxygen species (ROS). (prospecbio.com)
  • MutT protein of Escherichia coli and related mammalian enzymes specifically degrade 8-oxo-dGTP to 8-oxo-dGMP,thereby preventing occurrence of transversion mutation. (nii.ac.jp)
  • The N-terminal catalytic domain and the C-terminal zinc finger straddle the DNA with the long axis of the protein oriented roughly orthogonal to the helical axis of the DNA. (embl-heidelberg.de)
  • Fpg is a bilobal protein with awide, positively charged DNA-binding groove. (embl-heidelberg.de)
  • However, structural analysis alone of protein-nucleic acid interactions at a molecular level cannot provide quantitative estimates of the relative importance of molecular contacts, nor of the relative contributions of strong and weak, or specific and nonspecific, contacts to the total affinity of an enzyme for DNA. (jbsdonline.com)
  • Recently our analysis of the interactions involved for a DNA repair enzyme, 8-oxoguanine DNA glycosylase from E. coli (Fpg-protein), with DNA substrates (1) showed that the enzyme specificity is mostly kinetic than thermodynamic in its nature. (jbsdonline.com)
  • We have used presteady-state stopped-flow kinetic methods and protein fluorescence changes to resolve a dynamic questions of repair process catalyzed with 8-oxoguanine DNA glycosylases, E. coli Fpg-protein and human hOgg1 (2). (jbsdonline.com)
  • Using the twelve-nucleotide duplex d(CTCTCXCCTTCC) · d(GGAAGGCGAGAG), where where X = G, 8-oxoG, ribose (AP-nucleotide) and tetrahydrofuran (non-cleavable AP-nucleotide), and single-turnover conditions guiding the choice of enzyme concentrations, multiple transient changes in fluorescence were observed, indicating conformational transitions in the protein molecule. (jbsdonline.com)
  • Chakravarti D, Ibeanu GC, Tano K, Mitra S: Cloning and expression in Escherichia coli of a human cDNA encoding the DNA repair protein N-methylpurine-DNA glycosylase. (drugbank.ca)
  • The planar compound links to nucleobases through water displacement of one or both of its chloride groups, allowing cisplatin to form monoadducts to DNA or RNA, intrastrand DNA crosslinks, interstrand DNA crosslinks, and DNA-protein crosslinks. (wikipedia.org)
  • 2006), Professor Salas and her team described an important discovery: the protein p56 of virus 29 inhibits the activity of the cellular protein uracil-DNA-glycosylase (UDG). (innovations-report.com)
  • 2007), recounting how the viral protein p56 manages to inhibit the activity of the UDG enzyme. (innovations-report.com)
  • Their experiments show that the protein p56 conceals the part of the UDG enzyme that interacts with the damaged DNA so that there is no possibility of attachment. (innovations-report.com)
  • The protein p56 might accomplish this by imitating the structural characteristics of DNA in order to mislead the UDG enzyme. (innovations-report.com)
  • Base flipping involves rotation of backbone bonds in double‐stranded deoxyribonucleic acid (DNA) to expose an out‐of‐stack base, which can then be a substrate for an enzyme‐catalysed chemical reaction or for a specific protein binding interaction. (els.net)
  • M.HhaI complexed to its substrate DNA (Protein Data Bank code 1mht). (els.net)
  • AAG complexed to DNA containing a pyrrolidine abasic nucleotide (Protein Data Bank code 1bnk). (els.net)
  • Arita K, Ariyoshi M, Tochio H, Nakamura Y and Shirakawa M (2008) Recognition of hemi‐methylated DNA by the SRA protein UHRF1 by a base‐flipping mechanism. (els.net)
  • 2004) DNA binding and nucleotide flipping by the human DNA repair protein AGT. (els.net)
  • Duguid EM, Rice PA and He C (2005) The structure of the human AGT protein bound to DNA and its implications for damage detection. (els.net)
  • The DNMT3-like protein Dnmt3L is homologous to the other Dnmt3s but lacks catalytic activity, and Dnmt2 has sequence homology to all Dnmts but methylates cytoplasmic tRNA instead of DNA ( 11 ). (diabetesjournals.org)
  • This has allowed us to perform parallel monitoring of DNA/RNA modifications and protein profiling in various diseased tissues to aid e.g. biomarker discovery. (ntnu.no)
  • The first enzyme molecule to be isolated in pure crystalline form was urease, prepared from the jack bean in 1926 by American biochemist J. B. Sumner, who suggested, contrary to prevailing opinion, that the molecule was a protein protein, any of the group of highly complex organic compounds found in all living cells and comprising the most abundant class of all biological molecules. (thefreedictionary.com)
  • In the period from 1930 to 1936, pepsin pepsin, enzyme produced in the mucosal lining of the stomach that acts to degrade protein. (thefreedictionary.com)
  • Pepsin is one of three principal protein-degrading, or proteolytic, enzymes in the digestive system, the other two being chymotrypsin and trypsin. (thefreedictionary.com)
  • it was confirmed that the crystals were protein, and the protein nature of enzymes was thereby firmly established. (thefreedictionary.com)
  • In addition to its function in base excision repair, APE1 also regulates transcription factors such as p53, activator protein 1, Myb, and NF-κB, although the mechanism is not yet clear ( 16 - 19 ). (rupress.org)
  • The XRCC1 gene protein plays an important role in BER by serving as a scaffold for other repair enzymes and by recognizing single-strand DNA breaks. (aacrjournals.org)
  • This cell damage caused by oxidative and nitrosative stress leads to mitochondrial protein, DNA, and lipid modifications, which inhibits energy production and contractile function, potentially leading to cell necrosis and/or apoptosis. (frontiersin.org)
  • Quantitative comparison of damage to protein and DNA crystals separately is challenging, but many of the issues are circumvented by studying pre-formed biological nucleoprotein complexes where direct comparison of each component can be made under the same controlled conditions. (iucr.org)
  • Here a model protein-DNA complex C.Esp1396I is employed to investigate specific damage mechanisms for protein and DNA in a biologically relevant complex over a large dose range (2.07-44.63 MGy). (iucr.org)
  • Typical specific damage was observed for both the protein on particular amino acids and for the DNA on, for example, the cleavage of base-sugar N 1 -C and sugar-phosphate C-O bonds. (iucr.org)
  • Strikingly the DNA component was determined to be far more resistant to specific damage than the protein for the investigated dose range. (iucr.org)
  • At low doses the protein was observed to be susceptible to radiation damage while the DNA was far more resistant, damage only being observed at significantly higher doses. (iucr.org)
  • We thank Prof. Fabrice Confalonieri at University of Paris-Sud for providing the genomic DNA of T. gammatolerans EJ3. (springer.com)
  • Changes to the structure of DNA can cause mutations and genomic instability, leading to cancer. (news-medical.net)
  • The repair of damage to both DNA strands is particularly important in maintaining genomic integrity. (news-medical.net)
  • Alternative joining has an undefined mechanism for repairing double strand breaks but is known to risk genomic integrity by joining end breaks on different chromosomes. (news-medical.net)
  • Mammalian cells rely on vast interactive DNA repair networks to preserve genomic integrity in the face of constant genotoxic stress ( 1 ). (aacrjournals.org)
  • Loss of DNA repair fidelity predisposes cells to mutation, genomic instability, and carcinogenesis ( 2 ). (aacrjournals.org)
  • The genomic integrity of the cell is constantly threatened by DNA damage, nucleotide changes, deletions or recombinations, or epigenetic modifications, leading to mutations. (mdpi.com)
  • Apoptosis occurred as a result of irreparable or incompletely repaired genomic DNA, which is constantly subject to assault from intrinsic and environmental insults. (hindawi.com)
  • Furthermore, the improper repair of DSBs can lead to large scale genomic sequence rearrangements, such as translocations, insertions, and deletions [ 11 ], and an increased frequency of such rearrangements is often observed in aged cells [ 12 - 16 ]. (pubmedcentralcanada.ca)
  • We believe that our article will be of interest to Clinical Cancer Research because it adds novelty to the field of H. pylori pathogenesis by showing that H. pylori infection, both in vivo and in vitro , induces a decrease in repair activity and a transient mutator phenotype, contributing to epithelial gastric genomic instability and to its neoplastic transformation. (aacrjournals.org)
  • In the bulk of genomic DNA, most CpGs are methylated, whereas those located in a CpG island (where CpG sites cluster to form repetitive sequences) remain largely unmethylated ( 7 ). (diabetesjournals.org)
  • The minor groove intercalation loop (leucine-loop) in Uracil-DNA N-glycosylases (UNGs) undergoes significant conformational changes upon substrate interaction. (omicsonline.org)
  • Ahn J, Vu T, Novince Z, Guerrero-Santoro J, Rapic-Otrin V, Gronenborn AM (2010) HIV-1 Vpr loads uracil DNA glycosylase-2 onto DCAF1, a substrate recognition subunit of a cullin 4A-RING E3 ubiquitin ligase for proteasome-dependent degradation. (springer.com)
  • This article covers the most recent developments in our understanding of BER, with particular emphasis on the mechanistic aspects of this process, which have been made possible by the elucidation of the crystal structures of several glycosylases in complex with their respective substrates, substrate analogues and products. (uzh.ch)
  • A sequence alignment of the two enzymes revealed amino acid substitutions in and near the leucine-loop of cUNG which may increase the elasticity of the loop and thus explain the observed higher catalytic efficiency of cUNG compared to hUNG. (omicsonline.org)
  • The sequence of uracil-DNA glycosylase is extremely well conserved [ PMID: 2555154 ] in bacteria and eukaryotes as well as in herpes viruses. (ebi.ac.uk)
  • Of the thousands of random changes created every day in the DNA of a human cell by heat, metabolic accidents, radiation of various sorts, and exposure to substances in the environment, only a few accumulate as mutations in the DNA sequence. (nih.gov)
  • Such a high rate of random changes in the DNA sequence would have disastrous consequences for an organism. (nih.gov)
  • Additionally it catalyzes both the pyrophosphorolysis of DNA, a reaction which is the reverse of polymerization, and pyrophosphate exchange which represents a repetitive sequence of nucleotide addition and pyrophosphorolysis. (thefreedictionary.com)
  • In mismatch repair, the missed errors are later corrected by enzymes which recognize and excise the mismatched base to restore the original sequence. (news-medical.net)
  • Distortions in the DNA sequence, such as damage or mispairs, are specifically recognized and processed by DNA repair enzymes. (mdpi.com)
  • By using the generally accepted DNA sequence for binding CpxR (two tandem GTAAA motifs separated by a 5-bp linker, the CpxR box), DeWulf et al. (asm.org)
  • The glycine 12 to glutamic acid substitution does not affect the enzymatic activity of the enzyme but lies in what was predicted to be a mitochondrial targeting sequence (MTS). (nih.gov)
  • Publications] Ihara,K.: 'Requirement of the Pro-Cys-Ilis-Arg sequence for O^6-methyl-guanine-DNA methyltransferase netivity revenled by saturation mutngenesis with negntive and positive soreening' Molec.Gen.Genet.243・4. (nii.ac.jp)
  • These compounds intercalate into DNA at 5'-AT sequence sites and form thymidine adducts when activated in the presence of Ultra Violet-A (UV-A) rays . (wikipedia.org)
  • To date, six structural superfamilies of DNA repair glycosylases and newly identified (non‐repair) sequence‐specific DNA glycosylases all use base‐flipping mechanism to access the target base. (els.net)
  • Zhang Y, Li CC, Tang B, Zhang CY (2017) Homogeneously sensitive detection of multiple DNA glycosylases with intrinsically fluorescent nucleotides. (springer.com)
  • The DNA repair ability of a cell is vital to the integrity of its genome and thus to its normal functioning and that of the organism. (bionity.com)
  • Crystal structure of a G:T/U mismatch-specific DNA glycosylase: mismatch recognition by complementary-strand interactions. (ebi.ac.uk)
  • DNA strand breaks are often caused by internal and external factors. (wikibooks.org)
  • The enzyme polynucleotide kinase/phosphatase plays an important role in repairing DNA strand breaks by catalyzing the restoration of DNA's termini. (wikibooks.org)
  • DNA damage comes in different forms like: base modification and base loss and strand breaks. (wikibooks.org)
  • The enzyme PNKP carries 5'-kinase and 3'phosphatase activities that are essential for processing of single and double strand breaks at termini. (wikibooks.org)
  • Using topoisomerase, camptothecin prevents resultant strand rejoining, leaving a DNA-enzyme 'dead-end' complex. (wikibooks.org)
  • A collection of tens of thousands of DNA single-strand molecular probes capable of detecting specific genes or measuring gene expression in a sample of tissue. (thefreedictionary.com)
  • DNA hybrids can form under conditions that inhibit intra-strand base pairing in single-stranded DNA . (thefreedictionary.com)
  • The non-defective strand is used as a template with the damaged DNA on the other strand removed and replaced by the synthesis of new nucleotides. (news-medical.net)
  • A read-ahead function in archaeal DNA polymerases detects promutagenic template-strand uracil", Proc. (freepatentsonline.com)
  • Several lines of evidence have indicated that FDG is a rat homologue of single-strand-selective monofunctional uracil-DNA glycosylase (SMUG1). (sigmaaldrich.com)
  • Incompletely repaired methoxyamine-blocked AP sites lead to increases in single-strand breaks and double-strand breaks (DSB) as well as cell death ( 4 , 11 ). (aacrjournals.org)
  • However, neither DNA strand breakage nor altered cell viability was observed. (greenmedinfo.com)
  • This crosslink can occur within the same strand (intrastrand) or between opposite strands of double-stranded DNA (interstrand). (wikipedia.org)
  • Cells were treated with cigarette smoke condensate (CSC) for 72 h to assess the formation of single- and double-strand DNA breaks, measured by alkaline and neutral single cell gel electrophoresis assays, respectively. (pubmedcentralcanada.ca)
  • Both single- and double-strand DNA breaks were removed during the initial 24 h but no further removal of the damage was observed. (pubmedcentralcanada.ca)
  • These data show that CSC-mediated DNA strand breaks are highly persistent, and suggest that persistence of cigarette smoke-associated DNA damage in the presence of HPV infection may lead to increased mutations in cervical cells and ultimately higher cancer risk. (pubmedcentralcanada.ca)
  • In the mid-1960s the prevalent model for excision repair in bacteria implicated some sort of enzymatic activity that specifically recognises the presence of damaged nucleotides in DNA and incises the damaged DNA strand close to the site of damage, thereby facilitating subsequent excision of a fragment of DNA containing the offending nucleotide. (scielo.org.za)
  • Uracil incorporation can induce DNA strand breaks and apoptosis. (cornell.edu)
  • Significantly higher γ-H2AX foci in lymphocytes confirmed DNA double strand breaks in LVAD recipients. (medsci.org)
  • In this mechanism a new strand of DNA is tested for pairing with the template strand, prior to methylation. (varsitytutors.com)
  • Processing of U:G base pairs via U N-glycosylase 2 (UNG2) or MutSα generates further point mutations, predominantly at G:C or A:T base pairs, respectively, but it is unclear why processing is mutagenic. (biomedsearch.com)
  • We found that excision of AID-induced U by UNG2 occurs predominantly during G1 phase, inducing faithful repair, mutagenic processing, and class switching. (biomedsearch.com)
  • Vpr is released into the host cell cytoplasm to participate to the translocation of the preintegration complex (PIC) into the nucleus for integration of the viral DNA into the host genome. (springer.com)
  • UNG2 has a major role in "Base excision repair" (BER) whose main function is to maintain genome integrity by controlling DNA uracilation. (springer.com)
  • FU readily becomes incorporated into the DNA of drug-treated cells, and accumulation of FU in the genome, rather than uracil excision, is correlated with FU cytotoxicity in mammalian cells. (aacrjournals.org)
  • In eukaryotes, DNA methylation is detected in protists, fungi, plants, and animals ( 3 ) and plays important roles in the establishment of developmental programs ( 4 , 5 ) and in genome defense against parasitic mobile elements ( 6 ). (pnas.org)
  • The base-excision repair enzyme uracil-DNA glycosylase (UDG) plays a crucial role in the maintenance of genome integrity. (springer.com)
  • It is known that this enzyme, present in all living organisms, is involved in the DNA repair processes and hence, it avoids mutations in the cellular genome. (innovations-report.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)
  • Here, to test the hypothesis that the advent and decline of this culture was influenced by movements of people, we generated genome-wide ancient DNA from 22 individuals from Peqi'in Cave, Israel. (nature.com)
  • Previous genome-wide ancient DNA studies from the Near East have revealed that at the time when agriculture developed, populations from Anatolia, Iran, and the Levant were approximately as genetically differentiated from each other as present-day Europeans and East Asians are today 24 , 25 . (nature.com)
  • In the course of this experience and during two years I spent at the Walter Reed Army Institute of Research, I sought to understand some of the mysteries of a DNA repair process called excision repair, a process discovered in the 1960s, by which multiple types of damaged or inappropriately positioned nucleotides in DNA are excised from the genome. (scielo.org.za)
  • A 5-methylcytosine DNA glycosylase/DNA demethylase activity was also identified and partially purified from normal and cancerous humans cells ( 16 , 17 ), but the enzyme responsible for this demethylase activity has not yet been cloned. (pnas.org)
  • Research into PNKP has shown that small molecule inhibitors of these enzymes sensitize cells to IR or chemotherapeutic agents. (wikibooks.org)
  • The importance of DNA repair is evident from the large investment that cells make in DNA repair enzymes. (nih.gov)
  • These two reactions are the most frequent spontaneous chemical reactions known to create serious DNA damage in cells. (nih.gov)
  • dUTPase hydrolyses FdUTP as well as dUTP ( 11 ), and the significance of FU incorporation in DNA has been difficult to evaluate from the low levels measurable in drug-treated normal or tumor cells ( 12 - 15 ). (aacrjournals.org)
  • Moreover, this method can be used for the screening of enzyme inhibitors and the simultaneous detection of hOGG1 and hAAG from lung cancer cells, having great potential for further application in early clinical diagnosis. (rsc.org)
  • Inhibition of DNA base excision repair can sensitize cells to DNA‐damaging treatments. (els.net)
  • If the DNA damage is limited, PARP participates in the DNA repair process and allows cells to survive the insult. (els.net)
  • Fishel ML, He Y, Smith ML and Kelley MR (2007) Manipulation of base excision repair to sensitize ovarian cancer cells to alkylating agent temozolomide. (els.net)
  • Cultures of arrested cells, via contact inhibition or DNA damage, exhibited decreased Rb phosphorylation and increased Rb acetylation. (portlandpress.com)
  • OGG1 expression was inhibited in cells exposed to high glucose with concomitant increase in ROS production and more severe DNA damage as compared to control culture conditions, and these changes were further exacerbated by bupivacaine. (hindawi.com)
  • He explained that DNA repair can be seen as "a double-edged sword": If DNA can be repaired in healthy cells, even cancer cells are able to repair their own DNA and thus counteract all kinds of cancer treatment. (lindau-nobel.org)
  • These results imply that these cancer cells are deficient in their mitochondrial 8-oxoG DNA repair activity. (nih.gov)
  • Publications] Ishibashi,T.: 'Intracellular localization and function of DNA repair methyltransferase in human cells' Mutation Res.315・3. (nii.ac.jp)
  • Our results show that MPG-overexpressing IGROV-1 and IGROV-1mp53 cells are significantly more sensitive to the clinical chemotherapeutic temozolomide in combination with methoxyamine as assayed by cytotoxicity, apoptosis, and levels of DNA damage than either agent alone. (aacrjournals.org)
  • Although telomere length is not affected in the hematopoietic tissues of Nth1 −/− adult mice, telomeres suffer from attrition and increased recombination and DNA damage foci formation in Nth1 −/− bone marrow cells that are stimulated ex vivo in the presence of 20% oxygen. (prolekare.cz)
  • The fact that telomerase deficiency can exacerbate telomere shortening in Nth1 deficient mouse cells supports that base excision repair cooperates with telomerase to maintain telomere integrity. (prolekare.cz)
  • Inhibition of a DNA repair enzyme, OGG1, results in increased free radicals concentration and oxidative damage to Neuro-2a cells as a result of 900 MHz EMF exposure. (greenmedinfo.com)
  • 8-oxoG DNA glycosylase-1 inhibition sensitizes Neuro-2a cells to oxidative DNA base damage induced by 900 MHz radiofrequency electromagnetic radiation. (greenmedinfo.com)
  • The purpose of this study was to explore the in vitro putative genotoxicity during exposure of Neuro-2a cells to radiofrequency electromagnetic fields (RF-EMFs) with or without silencing of 8-oxoG DNA glycosylase-1 (OGG1). (greenmedinfo.com)
  • Exposure to 900 MHz RF-EMFs with insufficient energy could induce oxidative DNA base damage in Neuro-2a cells. (greenmedinfo.com)
  • Without OGG1 siRNA, 2 W/kg RF-EMFs induced oxidative DNA base damage in Neuro-2a cells. (greenmedinfo.com)
  • Interestingly, with OGG1 siRNA, RF-EMFs could cause DNA base damage in Neuro-2a cells as low as 1 W/kg. (greenmedinfo.com)
  • Damage tolerance is a measure of last resort to rescue cells from DNA damage. (genetics.org)
  • Without it, cells would become highly sensitive to killing by external and endogenously generated DNA-damaging agents. (genetics.org)
  • Samson L, Derfler B, Boosalis M, Call K: Cloning and characterization of a 3-methyladenine DNA glycosylase cDNA from human cells whose gene maps to chromosome 16. (drugbank.ca)
  • We thus conclude that TDG-dependent DNA repair has evolved to provide epigenetic stability in lineage committed cells. (uzh.ch)
  • therefore, we examined cigarette smoke-induced DNA damage and repair in HPV16-transformed human ectocervical cells (ECT1/E6 E7). (pubmedcentralcanada.ca)
  • To examine the DNA repair, cells were treated with CSC for 72 h, followed by CSC withdrawal and re-incubation of the cells with fresh medium for 24, 48, or 72 h. (pubmedcentralcanada.ca)
  • In AGS cells, the effect of H. pylori infection on base excision repair and mismatch repair (MMR) was analyzed by reverse transcription-PCR, Western blot, and activity assays. (aacrjournals.org)
  • DNA methylation has long been thought to be a static epigenetic mark, but emerging evidence suggests that it undergoes dynamic and reversible remodeling in somatic cells during developmental and pathogenic processes ( 12 , 13 ), making its machinery and effects attractive drug targets. (diabetesjournals.org)
  • DNA-repair enzymes help cells survive damage to their genomes, which arises as a normal byproduct of cell activity and can also be caused by environmental toxins. (mit.edu)
  • However, in certain situations, DNA repair can become harmful to cells, provoking an inflammatory response that produces severe tissue damage. (mit.edu)
  • Years of work failed to uncover the putative enzyme in extracts of bacteria that specifically recognise base damage generated by the exposure of cells to ultraviolet (UV) radiation, a naturally occurring mode of DNA damage associated with exposure of cells in the skin to sunlight. (scielo.org.za)
  • Together, these findings suggest that in proliferating embryonic cells, MYH might be primarily involved in post replicative repair of nuclear DNA, whereas in post mitotic neurons, in the repair of mitochondrial DNA. (utmb.edu)
  • The other cells in the retina are not affected at all, and they must experience the same amount of DNA damage. (technologynetworks.com)
  • These studies examined the effects of SHMT1 ablation on uracil incorporation, salvage thymidylate biosynthesis, dUTPase, and uracil repair in HeLa and A549 cells. (cornell.edu)
  • Conversely, treatment of HeLa cells with etoposide or cisplatin induced apoptosis, without increasing uracil levels in DNA, or decreasing TK1 or dUTPase expression. (cornell.edu)
  • This indicates uracil incorporation into DNA is critical to drug-mediated apoptosis in A549, but not HeLa cells. (cornell.edu)
  • Telomerase is an enzymatic multimolecular complex which has two known functions : 1) addition of [TTAGGG] repeats to telomeric DNA, counteracting normal mitotic erosion, and 2) activation of various genes controlling cell proliferation. (ens-lyon.fr)
  • The first is the transformation of urocanic acid into a immunosuppressing agent, and the other is the enzymatic action of the 8-oxoguanine glycosylase enzyme. (openthesis.org)
  • Publications] Ishibashi,T.: 'Artifieial control of nuclear translocation of DNA repair methy Itransferase' J.Biol.Chem.269・10. (nii.ac.jp)
  • The first step toward solving the mystery of antibody hypermutation and class switching came with the discovery of an enzyme essential for both activities in mice and humans, activation-induced cytidine deaminase (AID), by Tasuku Honjo and Anne Durandy. (jci.org)
  • In recent years, much progress has been made toward understanding the molecular mechanism of CSR because of the discovery that the enzyme activation-induced cytidine deaminase (AID) is required for CSR ( 2 , 3 ). (rupress.org)
  • Toxicity and repair of DNA adducts produced by the natural product yatakemycin, Nature Chemical Biology (2017). (phys.org)
  • The enzymes responsible for de novo as well as maintenance methylation at the 5′ position of cytosines have been well characterized, and mutations in these enzymes can release transcriptional gene silencing and cause various developmental phenotypes ( 2 , 3 , 6 , 7 ). (pnas.org)
  • Although DNA is a highly stable material, as required for the storage of genetic information, it is a complex organic molecule that is susceptible, even under normal cellular conditions, to spontaneous changes that would lead to mutations if left unrepaired ( Figure 5-46 ). (nih.gov)
  • The mutations would then be propagated throughout subsequent cell generations as the DNA is replicated. (nih.gov)
  • MYH glycosylase fixes this error so mutations do not accumulate in the DNA and lead to tumor formation. (medlineplus.gov)
  • Most mutations in this gene result in the production of a nonfunctional or low-functioning MYH glycosylase. (medlineplus.gov)
  • Immunoglobulin (Ig) affinity maturation requires the enzyme AID, which converts cytosines (C) in Ig genes into uracils (U). This alone produces C:G to T:A transition mutations. (biomedsearch.com)
  • Mutations arise from complex interactions between processes that damage DNA (exogenous and endogenous), prevent damage, and repair damage ( Zhou and Elledge 2000 ), and, like most traits, the rate of mutation is determined by an interaction of the environment and these genetic factors. (g3journal.org)
  • Mutations are believed to accumulate with age due to a combination of increased levels of endogenous DNA damaging agents, such as reactive oxygen species [ 3 ], and decreased efficiency and fidelity of DNA repair [ 4 - 8 ]. (pubmedcentralcanada.ca)
  • This study confirms the suggested importance of the leucine-loop for efficient catalysis of UNG and shows that it is possible to alter the catalytic capacity of this enzyme by manipulating the amino acid composition of this loop. (omicsonline.org)
  • For catalysis to occur the damaged nucleotide must be everted from DNA to expose its C1? (jbsdonline.com)
  • Here, we develop a single-molecule detection method for the simultaneous detection of human 8-oxoguanine DNA glycosylase 1 (hOGG1) and human alkyladenine DNA glycosylase (hAAG) on the basis of DNA glycosylase-mediated cleavage of molecular beacons. (rsc.org)
  • Recent research reveals that human 8-oxoguanine DNA glycosylase (hOGG1) 12,13 and human alkyladenine DNA glycosylase (hAAG) 14 may become biomarkers for lung cancer risk assessment and prevention. (rsc.org)
  • For example, analysis of the genomes of bacteria and yeasts has revealed that several percent of the coding capacity of these organisms is devoted solely to DNA repair functions. (nih.gov)
  • After 3 rounds of selection, the recovered phage library was introduced into host bacteria, individual clones were selected on LB agar plates, and the phage DNA corresponding to the peptide insert was sequenced with established primers by methods described previously ( 11 ). (aacrjournals.org)
  • While writing his doctoral thesis at the University of Texas in Dallas, he succeeded in cloning the gene for photolyase, an enzyme that can repair UV damage in DNA, and was even able to breed bacteria that could produce this enzyme. (lindau-nobel.org)
  • The Streptomyces bacteria that produce YTM have also evolved a special enzyme to protect their own DNA from the toxin. (news-medical.net)
  • Neuberger studied biochemistry at the University of Cambridge and began his scientific career with Brian Hartley at Imperial College London, working on the evolution of enzymes in bacteria. (jci.org)
  • However, after turning to extracts of bacteria infected with a bacteriophage called T4, I identified such an enzyme activity. (scielo.org.za)
  • Watanabe S, Ichimura T, Fujita N, Tsuruzoe S, Ohki I, Shirakawa M, Kawasuji M, Nakao M: Methylated DNA-binding domain 1 and methylpurine-DNA glycosylase link transcriptional repression and DNA repair in chromatin. (drugbank.ca)