Six Germline Genetic Variations Impair the Translesion Synthesis Activity of Human DNA Polymerase κ.

ABSTRACT: DNA polymerase (pol) κ efficiently catalyzes error-free translesion DNA synthesis (TLS) opposite bulky N²-guanyl lesions induced by carcinogens such as polycyclic aromatic hydrocarbons. We investigated the biochemical effects of nine human nonsynonymous germline POLK variations on the TLS properties of pol κ, utilizing recombinant pol κ (residues 1-526) enzymes and DNA templates containing an N²-CH₂(9-anthracenyl)G (N²-AnthG), 8-oxo-7,8-dihydroguanine (8-oxoG), O⁶-methyl(Me)G, or an abasic site. In steady-state kinetic analyses, the R246X, R298H, T473A, and R512W variants displayed 7- to 18-fold decreases in k_cat/K_m for dCTP insertion opposite G and N²-AnthG, with 2- to 3-fold decreases in DNA binding a

SUBMITTER: Kim JK 

PROVIDER: S-EPMC5116392 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature