Mechanism of mutagenesis by O6-methylguanine.
O6-methylguanine (O6meG) lesions of double-stranded DNA have been associated with mutation and neoplastic transformation. These lesions can, in principle, be produced by at least three different mechanisms: direct alkylation of G X C base pairs in double-stranded DNA; alkylation of guanine residues in single-stranded regions of DNA associated with replication forks; and alkylation of the DNA precursor pool followed by incorporation of O6-methyl deoxyguanosine triphosphate (O6-medGTP) during DNA replication. DNA biosynthesis subsequent to all three events will generate predominantly O6-meG X T base pairs as O6meG preferentially pairs with T. We show here that O6meG X T base pairs are mutagenic; that transalkylase repair has a direct role in the generation of mutations induced by alkylated pool nucleotides; and that the Escherichia coli mismatch repair system is capable of repairing mutagenic G X T intermediates.
D001483:Base Sequence; D003090:Coliphages / Q000235:genetics*; D004260:DNA Repair; D004261:DNA Replication / Q000187:drug effects; D004262:DNA Restriction Enzymes; D004279:DNA, Viral / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D005838:Genotype; D006147:Guanine / Q000031:analogs & derivatives* / Q000633:toxicity; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D010957:Plasmids; D014162:Transfection
D004279:DNA, Viral; D009153:Mutagens; D006147:Guanine; C008449:O-(6)-methylguanine; D004262:DNA Restriction Enzymes