Molecular Basis for Proofreading by the Unique Exonuclease Domain of Family-D DNA Polymerases

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Dec 14

PMID 38097591

Authors

Leonardo Betancurt-Anzola

Markel Martinez-Carranza

Marc Delarue

Kelly M Zatopek

Andrew F Gardner

Ludovic Sauguet

Affiliations

Soon will be listed here.

Abstract

Replicative DNA polymerases duplicate entire genomes at high fidelity. This feature is shared among the three domains of life and is facilitated by their dual polymerase and exonuclease activities. Family D replicative DNA polymerases (PolD), found exclusively in Archaea, contain an unusual RNA polymerase-like catalytic core, and a unique Mre11-like proofreading active site. Here, we present cryo-EM structures of PolD trapped in a proofreading mode, revealing an unanticipated correction mechanism that extends the repertoire of protein domains known to be involved in DNA proofreading. Based on our experimental structures, mutants of PolD were designed and their contribution to mismatch bypass and exonuclease kinetics was determined. This study sheds light on the convergent evolution of structurally distinct families of DNA polymerases, and the domain acquisition and exchange mechanism that occurred during the evolution of the replisome in the three domains of life.

Citing Articles

Communication between DNA polymerases and Replication Protein A within the archaeal replisome.

Martinez-Carranza M, Vialle L, Madru C, Cordier F, Tekpinar A, Haouz A Nat Commun. 2024; 15(1):10926.

PMID: 39738083 PMC: 11686378. DOI: 10.1038/s41467-024-55365-w.

Expression and functional study of DNA polymerases from sp. BL-248-WT-3 and FJAT-21963.

Sun Y, Ko D, Gao J, Fu K, Mao Y, He Y Front Microbiol. 2024; 15:1501020.

PMID: 39633807 PMC: 11615080. DOI: 10.3389/fmicb.2024.1501020.

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