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TitleStructure and mechanism of B-family DNA polymerase ζ specialized for translesion DNA synthesis.
Journal, issue, pagesNat Struct Mol Biol, Vol. 27, Issue 10, Page 913-924, Year 2020
Publish dateAug 17, 2020
AuthorsRadhika Malik / Mykhailo Kopylov / Yacob Gomez-Llorente / Rinku Jain / Robert E Johnson / Louise Prakash / Satya Prakash / Iban Ubarretxena-Belandia / Aneel K Aggarwal /
PubMed AbstractDNA polymerase ζ (Polζ) 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 ...DNA polymerase ζ (Polζ) 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 Polζ is unknown. We present cryo-EM structures of the Saccharomyces cerevisiae Polζ holoenzyme in the act of DNA synthesis (3.1 Å) and without DNA (4.1 Å). Polζ 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 Polζ's role in TLS and provide a framework for new cancer therapeutics.
External linksNat Struct Mol Biol / PubMed:32807989 / PubMed Central
MethodsEM (single particle)
Resolution3.1 - 4.1 Å
Structure data

21108

6v8p

EMDB-21108, PDB-6v8p:
Structure of DNA Polymerase Zeta (Apo)
Method: EM (single particle) / Resolution: 4.1 Å

21115

6v93

EMDB-21115, PDB-6v93:
Structure of DNA Polymerase Zeta/DNA/dNTP Ternary Complex
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-SF4:
IRON/SULFUR CLUSTER / Iron–sulfur cluster

ChemComp-CA:
Unknown entry

ChemComp-DCP:
2'-DEOXYCYTIDINE-5'-TRIPHOSPHATE / Deoxycytidine triphosphate

ChemComp-HOH:
WATER / Water

Source
  • saccharomyces cerevisiae (strain atcc 204508 / s288c) (yeast)
  • Saccharomyces cerevisiae (brewer's yeast)
  • synthetic construct (others)
KeywordsDNA BINDING PROTEIN / DNA REPLICATION / DNA REPAIR / TRANSLESION DNA SYNTHESIS / DNA POLYMERASE

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