Mutations in the mutY gene of Escherichia coli enhance the frequency of targeted G:C-->T:a transversions induced by a single 8-oxoguanine residue in single-stranded DNA.
Oxidative damage to guanine in DNA results in the formation of 8-oxoguanine, which has been shown to induce G-->T transversions targeted to this site. The mutagenicity of this lesion was studied in several mutator strains of Escherichia coli, using single-stranded DNA containing a single 8-oxoguanine residue. The frequencies of targeted G-->T transversions increased markedly in mutY strains, while this mutagenic event was not affected in mutM or mutS strains. Introduction of a mutM mutation into a mutY strain caused a somewhat higher frequency of G-->T transversions than that in the mutY strain and the effect of a mutS mutation was marginal. We conclude that the mutY gene plays a crucial role in preventing targeted G-->T mutations derived from misreplication of the 8-oxoguanine-containing template DNA.
Department of Pharmacological Sciences, State University of New York, Stony Brook 11794-8651.
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Moriya
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Grollman
D001483:Base Sequence; D004249:DNA Damage; D045647:DNA Glycosylases; D004269:DNA, Bacterial / Q000235:genetics*; D004277:DNA, Single-Stranded; D004926:Escherichia coli / Q000235:genetics*; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009699:N-Glycosyl Hydrolases / Q000235:genetics*
D004269:DNA, Bacterial; D004277:DNA, Single-Stranded; C024829:8-hydroxyguanine; D006147:Guanine; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; C061738:mutY adenine glycosylase