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-Structure paper
Title | Structure and mechanism of B-family DNA polymerase ζ specialized for translesion DNA synthesis. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 27, Issue 10, Page 913-924, Year 2020 |
Publish date | Aug 17, 2020 |
Authors | Radhika Malik / Mykhailo Kopylov / Yacob Gomez-Llorente / Rinku Jain / Robert E Johnson / Louise Prakash / Satya Prakash / Iban Ubarretxena-Belandia / Aneel K Aggarwal / |
PubMed Abstract | 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 ...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 links | Nat Struct Mol Biol / PubMed:32807989 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.1 - 4.1 Å |
Structure data | EMDB-21108, PDB-6v8p: EMDB-21115, PDB-6v93: |
Chemicals | ChemComp-SF4: ChemComp-CA: ChemComp-DCP: ChemComp-HOH: |
Source |
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Keywords | DNA BINDING PROTEIN / DNA REPLICATION / DNA REPAIR / TRANSLESION DNA SYNTHESIS / DNA POLYMERASE |