Replication Bypass of the <i>N</i>-(2-Deoxy-d-erythro-pentofuranosyl)-urea DNA Lesion by Human DNA Polymerase η.

ABSTRACT: Urea lesions in DNA arise from thymine glycol (Tg) or 8-oxo-dG; their genotoxicity is thought to arise in part due to their potential to accommodate the insertion of all four dNTPs during error-prone replication. Replication bypass with human DNA polymerase η (hPol η) confirmed that all four dNTPs were inserted opposite urea lesions but with purines exhibiting greater incorporation efficiency. X-ray crystal structures of ternary replication bypass complexes in the presence of Mg²⁺ ions with incoming dNTP analogs dAMPnPP, dCMPnPP, dGMPnPP, and dTMPnPP bound opposite urea lesions (hPol η·DNA·dNMPnPP complexes) revealed all were accommodated by hPol η. In each, the Watson-Crick face of the dNMPnPP was paired with the urea lesion, exploiting the ability of the amine and carbonyl gro

SUBMITTER: Tomar R 

PROVIDER: S-EPMC10956437 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature