Mutagenesis by damaged deoxyribonucleotides and its prevention by MutT-type hydrolyzing enzymes

Oxidized deoxyribonucleotides, 2-hydroxydeoxyadenosine 5'-triphosphate (2-OH-dATP) and 8-hydroxydeoxyguanosine 5'-triphosphate (8-OH-dGTP), were introduced into Escherichia coli strains deficient in DNA polymerase IV (a Y-family DNA polymerase encoded in the dinB gene), and the MutT and Orfl35 proteins to examine their in vivo roles in mutagenesis elicited by 2-OH-dATP and 8-OH-dGTP. 2-OH-dATP elicited mutations less efficiently in the dinB- strain than in the wild type strain, suggesting involvement of DNA polymerase IV in 2-OH-dATP-induced mutations. 8-OH-dGTP and 2-OH-dATP elicited mutations more efficiently in mutT- and orfl35- strains, respectively, than those in their isogenic mutT+ and orfl35+ strains. These results indicate that these proteins play important roles in mutagenesis induced by 2-OH-dATP and 8-OH-dGTP in vivo.