Mutagenic conformation of 8-oxo-7,8-dihydro-2′-dGTP in the confines of a DNA polymerase active site

Abstract

The major product of oxidative base damage is 8-oxo-7,8-dihydro-2′-deoxyguanine (8odG). The coding potential of this lesion is modulated by its glycosidic torsion angle that controls whether its Watson-Crick or Hoogsteen edge is utilized for base pairing. The 2.0 Å structure of DNA polymerase (pol) β bound with 8odGTP opposite template adenine indicates that the modified nucleotide assumes the mutagenic syn-conformation and that the non-mutagenic anti-conformation would be incompatible with efficient DNA synthesis.