Structural and dynamic characterization of polymerase κ's minor groove lesion processing reveals how adduct topology impacts fidelity.

ABSTRACT: DNA lesion bypass polymerases process different lesions with varying fidelities, but the structural, dynamic, and mechanistic origins of this phenomenon remain poorly understood. Human DNA polymerase κ (Polκ), a member of the Y family of lesion bypass polymerases, is specialized to bypass bulky DNA minor groove lesions in a predominantly error-free manner, by housing them in its unique gap. We have investigated the role of the unique Polκ gap and N-clasp structural features in the fidelity of minor groove lesion processing with extensive molecular modeling and molecular dynamics simulations to pinpoint their functioning in lesion bypass. Here we consider the N(2)-dG covalent adduct derived from the carcinogenic aromatic amine, 2-acetylaminofluorene (dG-N(2)-AAF), that is produced via the c

SUBMITTER: Lior-Hoffmann L 

PROVIDER: S-EPMC4159208 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature