Mechanism of error-free replication across benzo[a]pyrene stereoisomers by Rev1 DNA polymerase.

ABSTRACT: Benzo[a]pyrene (BP) is a carcinogen in cigarette smoke which, after metabolic activation, can react with the exocyclic N ² amino group of guanine to generate four stereoisomeric BP-N ²-dG adducts. Rev1 is unique among translesion synthesis DNA polymerases in employing a protein-template-directed mechanism of DNA synthesis opposite undamaged and damaged guanine. Here we report high-resolution structures of yeast Rev1 with three BP-N ²-dG adducts, namely the 10S (+)-trans-BP-N ²-dG, 10R (+)-cis-BP-N ²-dG, and 10S ( - )-cis-BP-N ²-dG. Surprisingly, in all three structures, the bulky and hydrophobic BP pyrenyl residue is entirely solvent-exposed in the major groove of the DNA. This is very different from the adduct alignments hi

SUBMITTER: Rechkoblit O 

PROVIDER: S-EPMC5645340 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature