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Structure of p15PAF–PCNA complex and implications for clamp sliding during DNA replication and repair

Author

Listed:
  • Alfredo De Biasio

    (Structural Biology Unit, CIC bioGUNE
    Present address: Elettra Sincrotrone Trieste, Trieste, Italy)

  • Alain Ibáñez de Opakua

    (Structural Biology Unit, CIC bioGUNE)

  • Gulnahar B. Mortuza

    (Structural Biology and Biocomputing Programme, Centro Nacional de Investigaciones Oncológicas
    Protein Structure and Function Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Rafael Molina

    (Structural Biology and Biocomputing Programme, Centro Nacional de Investigaciones Oncológicas)

  • Tiago N. Cordeiro

    (Centre de Biochimie Structurale, INSERM U1054, CNRS UMR 5048, Université Montpellier 1 and 2)

  • Francisco Castillo

    (Universidad de Granada, Fuentenueva s/n)

  • Maider Villate

    (Structural Biology Unit, CIC bioGUNE)

  • Nekane Merino

    (Structural Biology Unit, CIC bioGUNE)

  • Sandra Delgado

    (Structural Biology Unit, CIC bioGUNE)

  • David Gil-Cartón

    (Structural Biology Unit, CIC bioGUNE)

  • Irene Luque

    (Universidad de Granada, Fuentenueva s/n)

  • Tammo Diercks

    (Structural Biology Unit, CIC bioGUNE)

  • Pau Bernadó

    (Centre de Biochimie Structurale, INSERM U1054, CNRS UMR 5048, Université Montpellier 1 and 2)

  • Guillermo Montoya

    (Structural Biology and Biocomputing Programme, Centro Nacional de Investigaciones Oncológicas
    Universidad de Granada, Fuentenueva s/n)

  • Francisco J. Blanco

    (Structural Biology Unit, CIC bioGUNE
    IKERBASQUE, Basque Foundation for Science, María Díaz de Haro 3)

Abstract

The intrinsically disordered protein p15PAF regulates DNA replication and repair by binding to the proliferating cell nuclear antigen (PCNA) sliding clamp. We present the structure of the human p15PAF–PCNA complex. Crystallography and NMR show the central PCNA-interacting protein motif (PIP-box) of p15PAF tightly bound to the front-face of PCNA. In contrast to other PCNA-interacting proteins, p15PAF also contacts the inside of, and passes through, the PCNA ring. The disordered p15PAF termini emerge at opposite faces of the ring, but remain protected from 20S proteasomal degradation. Both free and PCNA-bound p15PAF binds DNA mainly through its histone-like N-terminal tail, while PCNA does not, and a model of the ternary complex with DNA inside the PCNA ring is consistent with electron micrographs. We propose that p15PAF acts as a flexible drag that regulates PCNA sliding along the DNA and facilitates the switch from replicative to translesion synthesis polymerase binding.

Suggested Citation

  • Alfredo De Biasio & Alain Ibáñez de Opakua & Gulnahar B. Mortuza & Rafael Molina & Tiago N. Cordeiro & Francisco Castillo & Maider Villate & Nekane Merino & Sandra Delgado & David Gil-Cartón & Irene L, 2015. "Structure of p15PAF–PCNA complex and implications for clamp sliding during DNA replication and repair," Nature Communications, Nature, vol. 6(1), pages 1-12, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7439
    DOI: 10.1038/ncomms7439
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    Cited by:

    1. Artur P. Kaczmarczyk & Anne-Cécile Déclais & Matthew D. Newton & Simon J. Boulton & David M. J. Lilley & David S. Rueda, 2022. "Search and processing of Holliday junctions within long DNA by junction-resolving enzymes," Nature Communications, Nature, vol. 13(1), pages 1-13, 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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