Mutations Induced by Oxidized DNA Precursors and Their Prevention by Nucleotide Pool Sanitization Enzymes

Abstract

Base oxidation occurs in the cellular nucleotide pool as well as in DNA, and the oxidized DNA precursors induce mutagenic events. 8-Hydroxy-dGTP (8-OH-dGTP) and 2-hydroxy-dATP (2-OH-dATP) have been identified as the major products of in vitro oxidation reactions with Fe2+. The mutagenic potentials of many oxidized DNA precursors have been examined in various experimental systems. Accumulating evidence indicates the importance of 8-OH-dGTP and 2-OH-dATP in the mutation process. In addition, nucleotide pool sanitization enzymes, such as MutT and MTH1, have been identified as a defense against the mutagenesis induced by these oxidized DNA precursors. In this review, the mutagenicities of 8-OH-dGTP and 2-OH-dATP and the functions of MutT-type nucleotide pool sanitization enzymes will be summarized. Key words: oxidized DNA precursor, 8-hydroxy-dGTP, 2-hydroxy-dATP, nucleotide pool sanitization enzyme. © 2007, The Japanese Environmental Mutagen Society. All rights reserved.