A novel role for Cdc5p in DNA replication

C F Hardy1, A Pautz

  • 1Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. chardy@cellbio.wustl.edu

Insights

The study reveals that Cdc5p, a mitotic kinase, may recruit to DNA replication origins, interacting with Dbf4p. This suggests a novel role for Polo-like kinases in DNA replication initiation.

Area of Science:

  • Molecular Biology
  • Cell Cycle Regulation
  • DNA Replication

Background:

  • DNA replication initiates at specific chromosomal origins occupied by the Origin Recognition Complex (ORC) in Saccharomyces cerevisiae.
  • Dbf4p is implicated in targeting the Cdc7p kinase to initiation complexes during the G1/S phase transition.

Purpose of the Study:

  • To investigate the potential role of Dbf4p in recruiting Cdc5p, a Polo family kinase, to DNA replication origin complexes.
  • To explore the functional interaction between Cdc5p, Cdc7p, Dbf4p, and ORC in DNA replication and cell division.

Main Methods:

  • Investigated protein-protein interactions between Dbf4p, Cdc5p, and Cdc7p using distinct domain interactions.
  • Utilized cdc5-1 mutants to assess plasmid maintenance defects and synthetic lethality with orc2-1 mutants.
  • Analyzed cell cycle regulation of Cdc5p protein levels.

Main Results:

  • Dbf4p interacts with distinct domains of both Cdc5p and Cdc7p, suggesting a scaffold function.
  • cdc5-1 mutants exhibit plasmid maintenance issues, suppressible by increased origin copy number.
  • Synthetic lethality observed in cdc5-1 orc2-1 double mutants indicates functional interdependence.
  • Cdc5p levels are cell cycle-regulated, peaking in G2/M phase.

Conclusions:

  • Cdc5p, a key mitotic kinase, likely plays a role at DNA replication origins, potentially recruited by Dbf4p.
  • These findings suggest a novel function for Polo-like kinases in the initiation of DNA replication.
  • The study highlights a potential link between mitotic progression and replication origin firing.

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