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 2.1.1.63.

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.

Guanine is a purine nucleobase, one of the four nucleobases in the nucleic acid of DNA and RNA, involved in forming hydrogen bonds between complementary base pairs in double-stranded DNA molecules.

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.

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.

A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed)

An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564)

Thymine is a pyrimidine nucleobase, one of the four nucleobases in the nucleic acid of DNA (the other three being adenine, guanine, and cytosine), where it forms a base pair with adenine.

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)

An enzyme that catalyzes the transfer of a methyl group from S-ADENOSYLMETHIONINE to the 5-position of CYTOSINE residues in DNA.

Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.

Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.

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.

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.

A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.

DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.

A nitrosoguanidine derivative with potent mutagenic and carcinogenic properties.

Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed)

Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)

Methylases that are specific for CYTOSINE residues found on DNA.

Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.

An enzyme responsible for producing a species-characteristic methylation pattern on adenine residues in a specific short base sequence in the host cell DNA. The enzyme catalyzes the methylation of DNA adenine in the presence of S-adenosyl-L-methionine to form DNA containing 6-methylaminopurine and S-adenosyl-L-homocysteine. EC 2.1.1.72.

In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.

A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.

Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.

Enzymes that catalyze the methylation of amino acids after their incorporation into a polypeptide chain. S-Adenosyl-L-methionine acts as the methylating agent. EC 2.1.1.

A pyrimidine base that is a fundamental unit of nucleic acids.

Physiologic methyl radical donor involved in enzymatic transmethylation reactions and present in all living organisms. It possesses anti-inflammatory activity and has been used in treatment of chronic liver disease. (From Merck, 11th ed)

Enzymes that catalyze the S-adenosyl-L-methionine-dependent methylation of ribonucleotide bases within a transfer RNA molecule. EC 2.1.1.

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).

An enzyme that catalyzes the methylation of the epsilon-amino group of lysine residues in proteins to yield epsilon mono-, di-, and trimethyllysine. EC 2.1.1.43.

A nitrosamine derivative with alkylating, carcinogenic, and mutagenic properties. It causes serious liver damage and is a hepatocarcinogen in rodents.

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.

A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

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.

Areas of increased density of the dinucleotide sequence cytosine--phosphate diester--guanine. They form stretches of DNA several hundred to several thousand base pairs long. In humans there are about 45,000 CpG islands, mostly found at the 5' ends of genes. They are unmethylated except for those on the inactive X chromosome and some associated with imprinted genes.

Enzymes that catalyze the methylation of arginine residues of proteins to yield N-mono- and N,N-dimethylarginine. This enzyme is found in many organs, primarily brain and spleen.

Interruption or suppression of the expression of a gene at transcriptional or translational levels.

A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression.

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.

A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.

A class of compounds that contain a -NH2 and a -NO radical. Many members of this group have carcinogenic and mutagenic properties.

A PROTEIN O-METHYLTRANSFERASE that recognizes and catalyzes the methyl esterification of ISOASPARTIC ACID and D-ASPARTIC ACID residues in peptides and proteins. It initiates the repair of proteins damaged by the spontaneous decomposition of normal L-aspartic acid and L-asparagine residues.

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.

Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.

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.

5'-S-(3-Amino-3-carboxypropyl)-5'-thioadenosine. Formed from S-adenosylmethionine after transmethylation reactions.

A purine base and a fundamental unit of ADENINE NUCLEOTIDES.

The rate dynamics in chemical or physical systems.

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.

A class of enzymes involved in the hydrolysis of the N-glycosidic bond of nitrogen-linked sugars.

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.

Nitrosourea compounds are a class of alkylating agents used in cancer chemotherapy, which contain a nitro group (NO2) and a urea functional group (R-NH-CO-NH2), known for their ability to cross the blood-brain barrier and damage DNA, thereby inhibiting tumor growth.

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.

Hydrazine substituted by one methyl group.

A pyrimidine nucleoside that is composed of the base CYTOSINE linked to the five-carbon sugar D-RIBOSE.

The products of chemical reactions that result in the addition of extraneous chemical groups to DNA.

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)

A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.

Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.

Histochemical localization of immunoreactive substances using labeled antibodies as reagents.

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.

An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA.

Established cell cultures that have the potential to propagate indefinitely.

The parts of a macromolecule that directly participate in its specific combination with another molecule.

The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.

A cell line derived from cultured tumor cells.

Uracil is a nitrogenous base, specifically a pyrimidine derivative, which constitutes one of the four nucleobases in the nucleic acid of RNA (ribonucleic acid), pairing with adenine via hydrogen bonds during base-pairing. (25 words)

Hydrazines substituted by one or more methyl groups in any position.

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.

Hydrazines substituted with two methyl groups in any position.

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).

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.

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)

Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.

The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.

The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.

A class of weak acids with the general formula R-CONHOH.

The process by which a DNA molecule is duplicated.

Proteins obtained from ESCHERICHIA COLI.

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.

The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.

Phosphate esters of THYMIDINE in N-glycosidic linkage with ribose or deoxyribose, as occurs in nucleic acids. (From Dorland, 28th ed, p1154)

RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.

A multisubunit polycomb protein complex that catalyzes the METHYLATION of chromosomal HISTONE H3. It works in conjunction with POLYCOMB REPRESSIVE COMPLEX 1 to effect EPIGENETIC REPRESSION.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.

Deoxyribonucleic acid that makes up the genetic material of bacteria.

An enzyme that catalyzes the transfer of methyl groups from S-adenosylmethionine to free carboxyl groups of a protein molecule forming methyl esters. EC 2.1.1.-.

Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.

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.

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.

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.

Inorganic salts of sulfurous acid.

An enzyme that catalyzes the METHYLATION of phosphatidyl-N-methylethanolamine to produce phosphatidyl-N-dimethylethanolamine. This enzyme can also methylate phosphatidyl-N-dimethylethanolamine to produce phosphatidyl-N-trimethylethanolamine (PHOSPHATIDYLCHOLINE).

A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.

A verocytotoxin-producing serogroup belonging to the O subfamily of Escherichia coli which has been shown to cause severe food-borne disease. A strain from this serogroup, serotype H7, which produces SHIGA TOXINS, has been linked to human disease outbreaks resulting from contamination of foods by E. coli O157 from bovine origin.

A DNA alkylating agent that has been shown to be a potent carcinogen and is widely used to induce colon tumors in experimental animals.

An essential amino acid. It is often added to animal feed.

Systems consisting of two enzymes, a modification methylase and a restriction endonuclease. They are closely related in their specificity and protect the DNA of a given bacterial species. The methylase adds methyl groups to adenine or cytosine residues in the same target sequence that constitutes the restriction enzyme binding site. The methylation renders the target site resistant to restriction, thereby protecting DNA against cleavage.

Enzyme systems containing a single subunit and requiring only magnesium for endonucleolytic activity. The corresponding modification methylases are separate enzymes. The systems recognize specific short DNA sequences and cleave either within, or at a short specific distance from, the recognition sequence to give specific double-stranded fragments with terminal 5'-phosphates. Enzymes from different microorganisms with the same specificity are called isoschizomers. EC 3.1.21.4.

The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.

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.

Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.

A group of compounds which consist of a nucleotide molecule to which an additional nucleoside is attached through the phosphate molecule(s). The nucleotide can contain any number of phosphates.

A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.

Compounds that inhibit HISTONE DEACETYLASES. This class of drugs may influence gene expression by increasing the level of acetylated HISTONES in specific CHROMATIN domains.

Proteins found in any species of bacterium.

5-Bromo-2,4(1H,3H)-pyrimidinedione. Brominated derivative of uracil that acts as an antimetabolite, substituting for thymine in DNA. It is used mainly as an experimental mutagen, but its deoxyriboside (BROMODEOXYURIDINE) is used to treat neoplasms.

A ZINC metalloenzyme that catalyzes the transfer of a methyl group from BETAINE to HOMOCYSTEINE to produce dimethylglycine and METHIONINE, respectively. This enzyme is a member of a family of ZINC-dependent METHYLTRANSFERASES that use THIOLS or selenols as methyl acceptors.