Mechanisms of chemical mutagenesis and carcinogenesis: effects on DNA replication of methylation at the O6-guanine position of dGTP.

The incorporation of O6-methyl-dGTP during DNA replication in vitro by 'Klenow' E. coli pol I was determined. O6-Methyl-dGTP was found to: (i) incorporate opposite T and C template residues, with a greater than 20-fold preference for T, and (ii) arrest DNA synthesis when incorporated in place of dATP at all but pyrimidine-rich growing-strand sequences. The significance of O6-methyl-dGTP incorporation during DNA biosynthesis in vivo for mutagenesis and carcinogenesis is discussed.