Effect of hyperoxidized guanine on DNA primer-template structures: Spiroiminodihydantoin leads to strand slippage.

摘要

Oxidation of guanine in DNA can lead to mutagenic lesions such as 7-hydro-8-oxoguanine (oG). Upon further oxidation, a more mutagenic lesion, spirominodihydantoin (Sp), can occur. In this study, nuclear magnetic resonance (NMR) investigations were performed to determine the structural features of DNA primer-template models with 5'-GG, 5'-G(oG), 5'-G(Sp) and 5'-T(Sp) templates, that mimic the situation in which the downstream G of the template has been oxidized to oG or hyperoxidized to Sp. Our results show that misalignment occurs only in the 5'-G(Sp) and 5'-T(Sp) templates, providing structural insights into the observed differences in mutagenicity of Sp and oG during DNA replication.