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PCNA, the maestro of the replication fork.

George-Lucian Moldovan1, Boris Pfander, Stefan Jentsch

  • 1Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18 82152 Martinsried, Germany.

Cell
|May 22, 2007
PubMed
Summary

Inheritance relies on accurate genome duplication and transmission. Proliferating cell nuclear antigen (PCNA) coordinates DNA replication and epigenetic inheritance by dynamically switching binding partners.

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Area of Science:

  • Molecular Biology
  • Epigenetics
  • Genetics

Background:

  • Inheritance necessitates genome duplication, chromatin reproduction, and epigenetic information transmission.
  • Proliferating cell nuclear antigen (PCNA) is a crucial cofactor for DNA polymerases, orchestrating replication and related functions by recruiting proteins to the replication fork.

Purpose of the Study:

  • To elucidate the mechanism by which Proliferating cell nuclear antigen (PCNA) coordinates multiple replication-linked processes.
  • To understand how Proliferating cell nuclear antigen (PCNA) manages interactions with various factors at the replication fork.

Main Methods:

  • Investigating protein-protein interactions at the replication fork.
  • Analyzing the role of Proliferating cell nuclear antigen (PCNA) in recruiting replication factors.
  • Examining post-translational modifications of Proliferating cell nuclear antigen (PCNA).

Main Results:

  • Many replication factors interact with Proliferating cell nuclear antigen (PCNA) via a common interaction domain.
  • These interactions do not occur concurrently, suggesting a dynamic switching mechanism.
  • Partner switching is regulated by factors including affinity competition, phosphorylation, proteolysis, and ubiquitination/SUMOylation of Proliferating cell nuclear antigen (PCNA).

Conclusions:

  • Proliferating cell nuclear antigen (PCNA) acts as a dynamic scaffold, regulating access of various factors to the replication fork.
  • The controlled switching of Proliferating cell nuclear antigen (PCNA) partners is essential for maintaining genome integrity and epigenetic inheritance during DNA replication.