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.