Excision repair of O6-methylguanine synthesized at the rat H-ras N-methyl-N-nitrosourea activation site and introduced into Escherichia coli

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Abstract
O6-methylguanine (O6-methylG) is believed to be the pre-mutagenic lesion responsible for mutational activation of the H-ras proto-oncogene in rats treated with N-methyl-N-nitro-sourea (MNU). Research on the repair of O6-methylG has primarily focused on the methyltransferases. Potentially, other repair proteins may be involved in repair of O6-methylG. We have investigated the effect of Escherichia coli UvrABC excision repair on O6-methylG synthesized at the rat H-ras MNU activation site in a partial rat H-ras sequence constructed in an M13mp vector. An oligonucleotide self-selection technique was used to identify progeny phage containing DNA replicated from the O6-methylG-containing strand. We found that excision repair can help protect against mutation by O6-methylG at the rat H-ras MNU activation site.