Structure and mechanism of B-family DNA polymerase ? specialized for translesion DNA synthesis.

ABSTRACT: DNA polymerase ? (Pol?) belongs to the same B-family as high-fidelity replicative polymerases, yet is specialized for the extension reaction in translesion DNA synthesis (TLS). Despite its importance in TLS, the structure of Pol? is unknown. We present cryo-EM structures of the Saccharomyces cerevisiae Pol? holoenzyme in the act of DNA synthesis (3.1?Å) and without DNA (4.1?Å). Pol? displays a pentameric ring-like architecture, with catalytic Rev3, accessory Pol31' Pol32 and two Rev7 subunits forming an uninterrupted daisy chain of protein-protein interactions. We also uncover the features that impose high fidelity during the nucleotide-incorporation step and those that accommodate mismatches and lesions during the extension reaction. Collectively, we decrypt the molecular underpinnings of Pol?'s role in TLS and provide a framework for new cancer therapeutics.

SUBMITTER: Malik R 

PROVIDER: S-EPMC7554088 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature