Increased A:T to C:G mutations in the mutT strain upon 8-hydroxy-dGTP treatment: Direct evidence for MutT in the prevention of mutations by oxidized dGTP

抄録

The Escherichia coli MutT protein hydrolyzes 8-hydroxy-dGTP (8-OH-dGTP) in vitro, and mutT gene deficiencies cause increased spontaneous A:T to C:G mutations. However, no direct evidence exists for the enhanced mutagenicity of 8-OH-dGTP in mutT cells. In this study, 8-OH-dGTP was introduced into wild type and mutT E. coli cells, and mutations on a chromosomal gene were monitored. 8-OH-dGTP induced mutations in the rpoB gene, and the degree of the mutation induction in the mutT strain was ~6-fold higher than that in the wild type strain. On the other hand, 2-hydroxy-dATP, which is not a substrate of the MutT protein, increased mutations to similar degrees in both strains. These results provide the first evidence showing that the MutT protein suppresses mutations by 8-OH-dGTP in vivo.