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Related Experiment Videos

Molecular modeling-based analysis of interactions in the RFC-dependent clamp-loading process.

Ceslovas Venclovas1, Michael E Colvin, Michael P Thelen

  • 1Computational and Systems Biology Division, Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, California 94550, USA. venclovas@llnl.gov

Protein Science : a Publication of the Protein Society
|September 19, 2002
PubMed
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Replication factor C (RFC) loads DNA polymerase clamps, but its mechanism is unclear. This study models RFC interactions with PCNA and Rad9-Rad1-Hus1 complexes, revealing subunit binding sites and proposing a structural arrangement for clamp loading.

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Biochemistry

Background:

  • Eukaryotic DNA replication and repair rely on Replication Factor C (RFC) to load sliding clamps, such as PCNA, onto DNA.
  • Understanding the precise molecular interactions and structural dynamics of RFC-clamp loading is crucial but limited by available data.
  • Alternative clamp loader complexes, like Rad17-RFC(2-5)/Rad9-Rad1-Hus1, also play vital roles in cellular processes.

Purpose of the Study:

  • To computationally model and analyze the interactions between RFC subunits and the PCNA clamp.
  • To elucidate the structural basis of clamp loading by RFC, including subunit arrangement and binding interfaces.
  • To map interactions within the alternative Rad17-RFC(2-5)/Rad9-Rad1-Hus1 clamp loader/clamp system.

Main Methods:

Related Experiment Videos

  • Computationally derived molecular models of RFC subunits and clamp complexes.
  • Integration of modeled structures with existing structural, biochemical, and genetic data.
  • Sequence and structure analysis of RFC subunits and their paralogs.

    • Main Results:

    • Detailed models of RFC1 and RFC3 interactions with PCNA's C-terminal regions are proposed, drawing parallels to known protein-protein interactions.
    • RFC5 is suggested as a third subunit interacting with PCNA.
    • A model for RFC and PCNA arrangement is proposed, with three RFC subunits binding PCNA and two subunits at PCNA interfaces.

    Conclusions:

    • The study provides a structural framework for understanding RFC-mediated clamp loading onto PCNA.
    • The proposed models offer specific, testable hypotheses for experimental validation.
    • Insights into the alternative Rad17-RFC(2-5)/Rad9-Rad1-Hus1 system are provided, furthering our understanding of clamp loader diversity.