FUNCTIONAL COOPERATION OF MUTT, MUTM AND MUTY PROTEINS IN PREVENTING MUTATIONS CAUSED BY SPONTANEOUS OXIDATION OF GUANINE-NUCLEOTIDE IN ESCHERICHIA-COLI

8-Oxo-dGTP (8-oxo-7,8-dihydrodeoxyguanosine triphosphate) is a potent mutagenic substrate for DNA synthesis. The accumulation of 8-oxo-dGTP in the nucleotide pool induces G:C --> T:A transversion as well as A:T --> C:G transversion, and Escherichia coli cells possess mechanisms for preventing such mutations. The murT gene product specifically hydrolyzes 8-oxo-dGTP to the monophosphate form while the mutM and the mutY gene products function to correct mispairs caused by incorporation of 8-oxoguanine into DNA. From analyses of forward mutations induced in cells lacking 8-oxo-dGTPase (MutT protein) and/or repair enzymes that suppress mutations caused by 8-oxoguanine in DNA (MutM and MutY proteins), cooperative functions of these proteins in control of the spontaneous mutagenesis became evident. In mutator strains lacking MutT and/or MutM proteins, 8-oxoguanine of DNA increased to a concentration expected from the increased rate of mutation.