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Structural basis of human PCNA sliding on DNA

Author

Listed:
  • Matteo De March

    (Structural Biology Laboratory, Elettra-Sincrotrone Trieste S.C.p.A.)

  • Nekane Merino

    (CIC bioGUNE, Parque Tecnologico de Bizkaia Edificio 800)

  • Susana Barrera-Vilarmau

    (Institute of Advanced Chemistry of Catalonia (IQAC), CSIC)

  • Ramon Crehuet

    (Institute of Advanced Chemistry of Catalonia (IQAC), CSIC)

  • Silvia Onesti

    (Structural Biology Laboratory, Elettra-Sincrotrone Trieste S.C.p.A.)

  • Francisco J. Blanco

    (CIC bioGUNE, Parque Tecnologico de Bizkaia Edificio 800
    IKERBASQUE, Basque Foundation for Science)

  • Alfredo De Biasio

    (Structural Biology Laboratory, Elettra-Sincrotrone Trieste S.C.p.A.)

Abstract

Sliding clamps encircle DNA and tether polymerases and other factors to the genomic template. However, the molecular mechanism of clamp sliding on DNA is unknown. Using crystallography, NMR and molecular dynamics simulations, here we show that the human clamp PCNA recognizes DNA through a double patch of basic residues within the ring channel, arranged in a right-hand spiral that matches the pitch of B-DNA. We propose that PCNA slides by tracking the DNA backbone via a ‘cogwheel’ mechanism based on short-lived polar interactions, which keep the orientation of the clamp invariant relative to DNA. Mutation of residues at the PCNA–DNA interface has been shown to impair the initiation of DNA synthesis by polymerase δ (pol δ). Therefore, our findings suggest that a clamp correctly oriented on DNA is necessary for the assembly of a replication-competent PCNA-pol δ holoenzyme.

Suggested Citation

  • Matteo De March & Nekane Merino & Susana Barrera-Vilarmau & Ramon Crehuet & Silvia Onesti & Francisco J. Blanco & Alfredo De Biasio, 2017. "Structural basis of human PCNA sliding on DNA," Nature Communications, Nature, vol. 8(1), pages 1-7, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms13935
    DOI: 10.1038/ncomms13935
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    Cited by:

    1. Sile F. Yang & Christopher B. Nelson & Jadon K. Wells & Madushan Fernando & Robert Lu & Joshua A. M. Allen & Lisa Malloy & Noa Lamm & Vincent J. Murphy & Joel P. Mackay & Andrew J. Deans & Anthony J. , 2024. "ZNF827 is a single-stranded DNA binding protein that regulates the ATR-CHK1 DNA damage response pathway," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Claudia Lancey & Muhammad Tehseen & Souvika Bakshi & Matthew Percival & Masateru Takahashi & Mohamed A. Sobhy & Vlad S. Raducanu & Kerry Blair & Frederick W. Muskett & Timothy J. Ragan & Ramon Crehuet, 2021. "Cryo-EM structure of human Pol κ bound to DNA and mono-ubiquitylated PCNA," Nature Communications, Nature, vol. 12(1), pages 1-14, December.

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