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

Nature. 2004 Jun 17;429(6993):724-30. doi: 10.1038/nature02585.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives*
  • Adenosine Triphosphate / metabolism
  • Binding Sites
  • DNA / chemistry*
  • DNA / metabolism*
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism*
  • Eukaryotic Cells
  • Models, Molecular
  • Nucleic Acid Conformation
  • Proliferating Cell Nuclear Antigen / chemistry*
  • Proliferating Cell Nuclear Antigen / metabolism*
  • Protein Conformation
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Replication Protein C
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae* / chemistry
  • Saccharomyces cerevisiae* / genetics


  • DNA-Binding Proteins
  • Proliferating Cell Nuclear Antigen
  • Protein Subunits
  • Saccharomyces cerevisiae Proteins
  • adenosine 5'-O-(3-thiotriphosphate)
  • Adenosine Triphosphate
  • DNA
  • Replication Protein C

Associated data

  • PDB/1SXJ