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Structural analysis of a eukaryotic sliding DNA clamp–clamp loader complex

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Listed:
  • Gregory D. Bowman

    (University of California
    Lawrence Berkeley National Laboratory)

  • Mike O'Donnell

    (The Rockefeller University)

  • John Kuriyan

    (University of California
    Lawrence Berkeley National Laboratory)

Abstract

Sliding clamps are ring-shaped proteins that encircle DNA and confer high processivity on DNA polymerases. Here we report the crystal structure of the five-protein clamp loader complex (replication factor-C, RFC) of the yeast Saccharomyces cerevisiae, bound to the sliding clamp (proliferating cell nuclear antigen, PCNA). Tight interfacial coordination of the ATP analogue ATP-γS by RFC results in a spiral arrangement of the ATPase domains of the clamp loader above the PCNA ring. Placement of a model for primed DNA within the central hole of PCNA reveals a striking correspondence between the RFC spiral and the grooves of the DNA double helix. This model, in which the clamp loader complex locks onto primed DNA in a screw-cap-like arrangement, provides a simple explanation for the process by which the engagement of primer–template junctions by the RFC:PCNA complex results in ATP hydrolysis and release of the sliding clamp on DNA.

Suggested Citation

  • Gregory D. Bowman & Mike O'Donnell & John Kuriyan, 2004. "Structural analysis of a eukaryotic sliding DNA clamp–clamp loader complex," Nature, Nature, vol. 429(6993), pages 724-730, June.
    • Handle: RePEc:nat:nature:v:429:y:2004:i:6993:d:10.1038_nature02585
    DOI: 10.1038/nature02585
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    Cited by:

    1. Zhichun Xu & Jianrong Feng & Daqi Yu & Yunjing Huo & Xiaohui Ma & Wai Hei Lam & Zheng Liu & Xiang David Li & Toyotaka Ishibashi & Shangyu Dang & Yuanliang Zhai, 2023. "Synergism between CMG helicase and leading strand DNA polymerase at replication fork," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Zhi-Qiang Xu & Slobodan Jergic & Allen T. Y. Lo & Alok C. Pradhan & Simon H. J. Brown & James C. Bouwer & Harshad Ghodke & Peter J. Lewis & Gökhan Tolun & Aaron J. Oakley & Nicholas E. Dixon, 2024. "Structural characterisation of the complete cycle of sliding clamp loading in Escherichia coli," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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