Mutagenic role of Watson-Crick protons in alkylated DNA bases: A theoretical study

Abstract

Loss of Watson-Crick protons following DNA base alkylation has been proposed as a key event which confers mutation-inducing properties on to alkylated DNA bases. In this theoretical study, the promutagenic O 6-guanine and O 4-thymine sites are clearly distinguished from the nonmutagenic N 7-guanine site on the basis of calculated values of mechanistic indicators for Watson-Crick proton acidity following alkylation at these respective sites. The degree of acidity predicted for these protons for each type of alkylated base accords well with the presence or absence of mutagenicity observed experimentally in each case.