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- Title
Mechanism of error-free replication across benzo [a]pyrene stereoisomers by Rev1 DNA polymerase.
- Authors
Rechkoblit, Olga; Landes, Hannah; Aggarwal, Aneel K.; Kolbanovskiy, Alexander; Geacintov, Nicholas E.
- Abstract
Benzo[a]pyrene (BP) is a carcinogen in cigarette smoke which, after metabolic activation, can react with the exocyclic N² amino group of guanine to generate four stereoisomeric BP-N²-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-N²-dG adducts, namely the 10S (+)-trans-BP-N²-dG, 10R (+)-cis-BP-N²-dG, and 10S ( - )-cis-BP-N²-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 hitherto observed in free or protein-bound DNA. All complexes are well poised for dCTP insertion. Our structures provide a view of cis-BP-N²-dG adducts in a DNA polymerase active site, and offer a basis for understanding error-free replication of the BP-derived stereoisomeric guanine adducts.
- Subjects
BENZOPYRENE; CARCINOGENESIS; CIGARETTE smoke; DNA polymerases; DNA synthesis
- Publication
Nature Communications, 2017, Vol 8, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-017-01013-5