Bulky Lesion Bypass Requires Dpo4 Binding in Distinct Conformations.

ABSTRACT: Translesion DNA synthesis is an essential process that helps resume DNA replication at forks stalled near bulky adducts on the DNA. Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon (PAH) that can be metabolically activated to benzo[a]pyrene diol epoxide (BPDE), which then can react with DNA to form carcinogenic DNA adducts. Here, we have used single-molecule florescence resonance energy transfer (smFRET) experiments, classical molecular dynamics simulations, and nucleotide incorporation assays to investigate the mechanism by which the model Y-family polymerase, Dpo4, bypasses a (+)-cis-B[a]P-N ²-dG adduct in DNA. Our data show that when (+)-cis-B[a]P-N ²-dG is the templating base, the B[a]P moiety is in a non-solvent exposed conformation stacked within the

SUBMITTER: Liyanage PS 

PROVIDER: S-EPMC5727293 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature