Biomaterial Database

O6-Alkylguanine-DNA alkyltransferase: influence on susceptibility to the genetic effects of alkylating agents. 1998

S A Kyrtopoulos

Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece. skyrt@eie.gr

O6-Alkylguanine-DNA alkyltransferase (AGT) repairs DNA containing O6-alkylguanine by a suicide mechanism involving transfer of the alkyl group to its active site. In this way AGT protects cells from the mutagenic and cytotoxic effects of O6-alkylguanine-type lesions such as O6-methylguanine (O6-meG), an observation which has during recent years been confirmed by studies in transgenic animals either over-expressing or completely lacking this activity. While the levels of expression of AGT have been shown to affect strongly the repair of O6-meG after high doses of methylating agents inducing complete and prolonged depletion of the cellular AGT pool, other data suggest that within smaller variations of AGT levels (such as the interindividual variations observed in man or as observed after low or moderate exposures to alkylating agents) the dependence of O6-meG repair is limited. This phenomenon may reflect the intracellular distribution of the repair protein and must be taken into account when assessing the role of AGT in determining susceptibility to alkylating agents of environmental or clinical significance.

UI	MeSH Term	Description	Entries
D008745	Methylation	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)	Methylations
D004247	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).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004260	DNA Repair	The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones.	DNA Damage Response
D006147	Guanine
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000477	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.	Alkylating Agent,Alkylator,Alkylators,Agent, Alkylating,Agents, Alkylating
D019853	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 2.1.1.63.	Methylated-DNA-Protein-Cysteine S-Methyltransferase,O(6)-AGT,O(6)-Methylguanine Methyltransferase,DNA Repair Methyltransferase I,DNA Repair Methyltransferase II,Guanine-O(6)-Alkyltransferase,O(6)-Alkylguanine-DNA Alkyltransferase,O(6)-MeG-DNA Methyltransferase,O(6)-Methylguanine DNA Transmethylase,Methylated DNA Protein Cysteine S Methyltransferase,S-Methyltransferase, Methylated-DNA-Protein-Cysteine