Mechanisms of glycosylase-induced mutagenesis

Mutator phenotypes are implicated in the development of human cancers. The base excision repair pathway has been connected to mild mutator phenotypes. When the initiating enzymes of the BER pathway, glycosylases, are overexpressed, small increases in point mutations and in indels in homopolymers are observed in reporter assays. This study passaged yeast strains overexpressing the human AAG glycosylase for 1000 generations and identified resulting mutations. The results indicate the importance of enzymatic specificity for restricting mutagenesis by repair enzymes.