How DNA polymerase X preferentially accommodates incoming dATP opposite 8-oxoguanine on the template.

ABSTRACT: The modified base 8-oxo-7,8-dihydro-2'-deoxyguanosine (oxoG) is a common DNA adduct produced by the oxidation of DNA by reactive oxygen species. Kinetic data reveal that DNA polymerase X (pol X) from the African swine fever virus incorporates adenine (dATP) opposite to oxoG with higher efficiency than the non-damaged G:C basepair. To help interpret the kinetic data, we perform molecular dynamics simulations of pol X/DNA complexes, in which the template base opposite to the incoming dNTP (dCTP, dATP, dGTP) is oxoG. Our results suggest that pol X accommodates the oxoGsyn:A mispair by sampling closed active conformations that mirror those observed in traditional Watson-Crick complexes. Moreover, for both the oxoGsyn:A and oxoG:C ternary complexes, conformational sampling of the polymerase fol

SUBMITTER: Sampoli Benitez B 

PROVIDER: S-EPMC3853083 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature