Polymerase bypass of N7-guanine monoadducts of cisplatin, diepoxybutane, and epichlorohydrin

Abstract

DNA oligonucleotides containing site-specific N7-guanine monoadducts of cisplatin, diepoxybutane, and epichlorohydrin were used as templates for DNA synthesis by two bacterial DNA polymerases and human polymerase β. These polymerases were able to bypass the lesions effectively, although the efficiency was decreased, with inhibition increasing with the size of the lesion. Fidelity of incorporation was essentially unaltered, suggesting that N7-guanine monoadducts do not significantly contribute to the mutational spectra of these agents.

A formamidopyrimidine derivative from the deoxyguanosine adduct produced by food contaminant acrylamide induces DNA replication block and mutagenesis

“…Notably, they incorporated a single base opposite GA-FAPy-dfG; however, almost no further extended products were observed. We also examined whether Polβ, which has been reported to bypass N7-dG monoadducts ( 47 ), can incorporate nucleotides opposite GA-FAPy-dfG. In contrast to the Y-family Pols, no nucleotide incorporation was observed with Polβ.…”