Molecular Mechanisms of Spontaneous Mutagenesis Caused by Oxygen Radicals

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8-Oxo-dGTP (8-oxo-7,8-dihydrodeoxyguanosine triphosphate) is a potent mutagenic substrate for DNA synthesis, and organisms possess enzymes specifically hydfolyzing 8-oxo-dGTP to the monophosphate form. The accumulatiom 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. From analyzes of forward mutations induced in cells lacking 8-oxo-dGTPase (MutT protein) and/or repair enzymes that suppress mutations caused by 8-oxoguanine 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 frequency of mutation.