Influence of local sequence context on damaged base conformation in human DNA polymerase iota: molecular dynamics studies of nucleotide incorporation opposite a benzo[a]pyrene-derived adenine lesion.

ABSTRACT: Human DNA polymerase iota is a lesion bypass polymerase of the Y family, capable of incorporating nucleotides opposite a variety of lesions in both near error-free and error-prone bypass. With undamaged templating purines polymerase iota normally favors Hoogsteen base pairing. Polymerase iota can incorporate nucleotides opposite a benzo[a]pyrene-derived adenine lesion (dA*); while mainly error-free, the identity of misincorporated bases is influenced by local sequence context. We performed molecular modeling and molecular dynamics simulations to elucidate the structural basis for lesion bypass. Our results suggest that hydrogen bonds between the benzo[a]pyrenyl moiety and nearby bases limit the movement of the templating base to maintain the anti glycosidic bond conformation in the binary

SUBMITTER: Donny-Clark K 

PROVIDER: S-EPMC2790882 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature