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Nature 429, 724-730 (17 June 2004) | doi:10.1038/nature02585; Received 27 February 2004; Accepted 20 April 2004

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

Gregory D. Bowman1,2, Mike O'Donnell3 & John Kuriyan1,2

  1. Howard Hughes Medical Institute, Department of Molecular and Cell Biology and Department of Chemistry, University of California, Berkeley, California 94720, USA
  2. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
  3. Laboratory of DNA Replication, Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10021, USA

Correspondence to: John Kuriyan1,2 Email: kuriyan@berkeley.edu
The coordinates and structure factors have been deposited in the Protein Data Bank (accession code 1SXJ).

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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-gammaS 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.

  1. Howard Hughes Medical Institute, Department of Molecular and Cell Biology and Department of Chemistry, University of California, Berkeley, California 94720, USA
  2. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
  3. Laboratory of DNA Replication, Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10021, USA

Correspondence to: John Kuriyan1,2 Email: kuriyan@berkeley.edu
The coordinates and structure factors have been deposited in the Protein Data Bank (accession code 1SXJ).

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