6v93 › Citations

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

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Malik R, Kopylov M, Gomez-Llorente Y, Jain R, Johnson RE, Prakash L, Prakash S, Ubarretxena-Belandia I, Aggarwal AK
OpenAccess logo Nat Struct Mol Biol 27 913-924 (2020)
Cited: 31 times
EuropePMC logo PMID: 32807989

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 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.

Reviews - 6v93 mentioned but not cited (1)

  1. REV7 directs DNA repair pathway choice. Clairmont CS, D'Andrea AD. Trends Cell Biol 31 965-978 (2021)

Articles - 6v93 mentioned but not cited (4)

  1. Structure and mechanism of B-family DNA polymerase ζ specialized for translesion DNA synthesis. Malik R, Kopylov M, Gomez-Llorente Y, Jain R, Johnson RE, Prakash L, Prakash S, Ubarretxena-Belandia I, Aggarwal AK. Nat Struct Mol Biol 27 913-924 (2020)
  2. Cryo-EM structure of translesion DNA synthesis polymerase ζ with a base pair mismatch. Malik R, Johnson RE, Prakash L, Prakash S, Ubarretxena-Belandia I, Aggarwal AK. Nat Commun 13 1050 (2022)
  3. Cryo-EM reveals conformational flexibility in apo DNA polymerase ζ. Du Truong C, Craig TA, Cui G, Botuyan MV, Serkasevich RA, Chan KY, Mer G, Chiu PL, Kumar R. J Biol Chem 297 100912 (2021)
  4. Evolution of Rev7 interactions in eukaryotic TLS DNA polymerase Polζ. McPherson KS, Rizzo AA, Erlandsen H, Chatterjee N, Walker GC, Korzhnev DM. J Biol Chem 299 102859 (2023)


Reviews citing this publication (9)

  1. Making Choices: DNA Replication Fork Recovery Mechanisms. Kondratick CM, Washington MT, Spies M. Semin Cell Dev Biol 113 27-37 (2021)
  2. REV7: Jack of many trades. de Krijger I, Boersma V, Jacobs JJL. Trends Cell Biol 31 686-701 (2021)
  3. DNA Polymerases at the Eukaryotic Replication Fork Thirty Years after: Connection to Cancer. Pavlov YI, Zhuk AS, Stepchenkova EI. Cancers (Basel) 12 E3489 (2020)
  4. Mechanisms for Maintaining Eukaryotic Replisome Progression in the Presence of DNA Damage. Guilliam TA. Front Mol Biosci 8 712971 (2021)
  5. Post-Translational Modifications of PCNA: Guiding for the Best DNA Damage Tolerance Choice. Bellí G, Colomina N, Castells-Roca L, Lorite NP. J Fungi (Basel) 8 621 (2022)
  6. Beyond the Lesion: Back to High Fidelity DNA Synthesis. Kaszubowski JD, Trakselis MA. Front Mol Biosci 8 811540 (2021)
  7. Recent Advances in Understanding the Structures of Translesion Synthesis DNA Polymerases. Ling JA, Frevert Z, Washington MT. Genes (Basel) 13 915 (2022)
  8. Repair and tolerance of DNA damage at the replication fork: A structural perspective. Eichman BF. Curr Opin Struct Biol 81 102618 (2023)
  9. Epigenetic Reader Bromodomain-Containing Protein 4 in Aging-Related Vascular Pathologies and Diseases: Molecular Basis, Functional Relevance, and Clinical Potential. Zheng X, Diktonaite K, Qiu H. Biomolecules 13 1135 (2023)

Articles citing this publication (17)

  1. MAD2L2 dimerization and TRIP13 control shieldin activity in DNA repair. de Krijger I, Föhr B, Pérez SH, Vincendeau E, Serrat J, Thouin AM, Susvirkar V, Lescale C, Paniagua I, Hoekman L, Kaur S, Altelaar M, Deriano L, Faesen AC, Jacobs JJL. Nat Commun 12 5421 (2021)
  2. Molecular mechanisms of assembly and TRIP13-mediated remodeling of the human Shieldin complex. Xie W, Wang S, Wang J, de la Cruz MJ, Xu G, Scaltriti M, Patel DJ. Proc Natl Acad Sci U S A 118 e2024512118 (2021)
  3. Structural understanding of non-nucleoside inhibition in an elongating herpesvirus polymerase. Hayes RP, Heo MR, Mason M, Reid J, Burlein C, Armacost KA, Tellers DM, Raheem I, Shaw AW, Murray E, McKenna PM, Abeywickrema P, Sharma S, Soisson SM, Klein D. Nat Commun 12 3040 (2021)
  4. Approaches to Using the Chameleon: Robust, Automated, Fast-Plunge cryoEM Specimen Preparation. Levitz TS, Weckener M, Fong I, Naismith JH, Drennan CL, Brignole EJ, Clare DK, Darrow MC. Front Mol Biosci 9 903148 (2022)
  5. Oxaliplatin promotes siMAD2L2‑induced apoptosis in colon cancer cells. Ma L, Li X, Zhao X, Sun H, Kong F, Li Y, Sui Y, Xu F. Mol Med Rep 24 629 (2021)
  6. Fe-S coordination defects in the replicative DNA polymerase delta cause deleterious DNA replication in vivo and subsequent DNA damage in the yeast Saccharomyces cerevisiae. Chanet R, Baïlle D, Golinelli-Cohen MP, Riquier S, Guittet O, Lepoivre M, Huang ME, Vernis L. G3 (Bethesda) 11 jkab124 (2021)
  7. DNA polymerase λ promotes error-free replication through Watson-Crick impairing N1-methyl-deoxyadenosine adduct in conjunction with DNA polymerase ζ. Yoon JH, Basu D, Choudhury JR, Prakash S, Prakash L. J Biol Chem 297 100868 (2021)
  8. Structure of DNA polymerase ζ: capturing the getaway driver. Washington MT, Gildenberg MS. Nat Struct Mol Biol 27 1-2 (2020)
  9. p31comet and TRIP13 recycle Rev7 to regulate DNA repair. Corbett KD. Proc Natl Acad Sci U S A 117 27761-27763 (2020)
  10. Knockdown of DNA polymerase ζ relieved the chemoresistance of glioma via inhibiting the PI3K/AKT signaling pathway. Yang J, Ding W, Wang X, Xiang Y. Bioengineered 12 3924-3933 (2021)
  11. Mismatch repair operates at the replication fork in direct competition with mismatch extension by DNA polymerase δ. Klassen R, Gangavarapu V, Johnson RE, Prakash L, Prakash S. J Biol Chem 299 104598 (2023)
  12. Canonical binding of Chaetomium thermophilum DNA polymerase δ/ζ subunit PolD3 and flap endonuclease Fen1 to PCNA. Alphey MS, Wolford CB, MacNeill SA. Front Mol Biosci 10 1320648 (2023)
  13. DNA Polymerase ζ without the C-Terminus of Catalytic Subunit Rev3 Retains Characteristic Activity, but Alters Mutation Specificity of Ultraviolet Radiation in Yeast. Siebler HM, Cui J, Hill SE, Pavlov YI. Genes (Basel) 13 1576 (2022)
  14. Implications of Translesion DNA Synthesis Polymerases on Genomic Stability and Human Health. Venkadakrishnan J, Lahane G, Dhar A, Xiao W, Bhat KM, Pandita TK, Bhat A. Mol Cell Biol 43 401-425 (2023)
  15. Polymerase ζ Is Involved in Mitochondrial DNA Maintenance Processes in Concert with APE1 Activity. Schreier HK, Wiehe RS, Ricchetti M, Wiesmüller L. Genes (Basel) 13 879 (2022)
  16. REV7 Monomer Is Unable to Participate in Double Strand Break Repair and Translesion Synthesis but Suppresses Mitotic Errors. Vassel FM, Laverty DJ, Bian K, Piett CG, Hemann MT, Walker GC, Nagel ZD. Int J Mol Sci 24 15799 (2023)
  17. Shieldin complex assembly kinetics and DNA binding by SHLD3. Susvirkar V, Faesen AC. Commun Biol 6 384 (2023)


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