The peroxidation-derived DNA adduct, 6-oxo-M₁dG, is a strong block to replication by human DNA polymerase η.

ABSTRACT: The DNA adduct 6-oxo-M₁dG, (3-(2'-deoxy-β-D-erythro-pentofuranosyl)-6-oxo-pyrimido(1,2alpha)purin-10(3H)-one) is formed in the genome via oxidation of the peroxidation-derived adduct M₁dG. However, the effect of 6-oxo-M₁dG adducts on subsequent DNA replication is unclear. Here we investigated the ability of the human Y-family polymerase hPol η to bypass 6-oxo-M₁dG. Using steady-state kinetics and analysis of DNA extension products by liquid chromatography-tandem mass spectrometry, we found hPol η preferentially inserts a dAMP or dGMP nucleotide into primer-templates across from the 6-oxo-M₁dG adduct, with dGMP being slightly preferred. We also show primer-templates with a 3'-terminal dGMP or dAMP across from 6-oxo-M₁dG were

SUBMITTER: Richie-Jannetta R 

PROVIDER: S-EPMC10450521 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature