Genetic evidence for nucleotide excision repair of O6-alkylguanine in mammalian cells.
Human cells that lack O6-alkylguanine DNA alkyltransferase (AT) activity can remove O6-butylguanine (O6-nBuG) produced in cellular DNA by exposure to N-n-butyl-N-nitrosourea as determined by radioimmunoassay of enzyme digests of DNA. Fibroblasts from xeroderma pigmentosum (XP) complementation groups A and G that show less than 5% unscheduled DNA synthesis following exposure to UVC failed to remove O6-nBuG. Hence it appears that O6-alkylguanine is repaired in cells that lack AT by a process that is defective in XP cells, presumably nucleotide excision repair. Neither V79 nor V79/79 Chinese hamster cell lines have AT activity and both are able to remove O6-nBuG from DNA. However, only V79/79 is able to remove O6MeG, suggesting some substrate specificity of the excision repair process. Comparison of relative levels of O6-alkylation by N-methyl-, N-ethyl-, N-propyl- and N-n-butyl-nitrosourea indicate that approximately equal levels of O6-alkylation are produced by equitoxic doses of these agents.
D000478:Alkylation; D000818:Animals; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000032:analysis; D004260:DNA Repair; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D008780:Methyltransferases / Q000378:metabolism; D009607:Nitrosourea Compounds / Q000494:pharmacology; D019853:O(6)-Methylguanine-DNA Methyltransferase; D011863:Radioimmunoassay; D014983:Xeroderma Pigmentosum
D009607:Nitrosourea Compounds; D006147:Guanine; C046953:O(6)-n-butylguanine; D004247:DNA; C008449:O-(6)-methylguanine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase