Molecular basis for proofreading by the unique exonuclease domain of Family-D DNA polymerases

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 poly...

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Bibliographic Details
Published in:Nature communications 2023-12, Vol.14 (1), p.8306-8306, Article 8306
Main Authors: Betancurt-Anzola, Leonardo, Martínez-Carranza, Markel, Delarue, Marc, Zatopek, Kelly M., Gardner, Andrew F., Sauguet, Ludovic
Format: Article
Language:English
Subjects:
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Archaea
Biological evolution
Deoxyribonucleic acid
DNA
DNA polymerase
DNA-directed DNA polymerase
DNA-directed RNA polymerase
Editing
Exonuclease
Genomes
Humanities and Social Sciences
Life Sciences
MRE11 protein
multidisciplinary
Proofreading
Proteins
RNA polymerase
Science
Science (multidisciplinary)
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Summary: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. Family D replicative DNA polymerases (PolD) contain a unique proofreading active site. Here, the authors present structures of PolD and enzymatic studies, revealing an unanticipated correction mechanism that extends the repertoire of protein domains known to be involved in DNA proofreading.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-44125-x