Enzymatic bypass and the structural basis of miscoding opposite the DNA adduct 1,N²-ethenodeoxyguanosine by human DNA translesion polymerase η.

ABSTRACT: Etheno (ε)-adducts, e.g., 1,N²-ε-guanine (1,N²-ε-G) and 1,N⁶-ε-adenine (1,N⁶-ε-A), are formed through the reaction of DNA with metabolites of vinyl compounds or with lipid peroxidation products. These lesions are known to be mutagenic, but it is unknown how they lead to errors in DNA replication that are bypassed by DNA polymerases. Here we report the structural basis of misincorporation frequencies across from 1,N²-ε-G by human DNA polymerase (hpol) η. In single-nucleotide insertions opposite the adduct 1,N²-ε-G, hpol η preferentially inserted dGTP, followed by dATP, dTTP, and dCTP. This preference for purines was also seen in the first extension step. Analysis of full-length extension products by LC-MS/MS revealed that G a

SUBMITTER: Ghodke PP 

PROVIDER: S-EPMC8121704 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature