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Related Experiment Videos

CDC7 kinase complex as a molecular switch for DNA replication.

H Masai1, N Sato, T Takeda

  • 1Department of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan and CREST, Japan Science Technology. hisao@ims.u-tokyo.ac.jp

Frontiers in Bioscience : a Journal and Virtual Library
|November 30, 1999
PubMed
Summary

The Cdc7 kinase and Dbf4 activator protein complex is essential for DNA replication in eukaryotes. Its activity is tightly regulated during the cell cycle, impacting DNA synthesis and chromatin structure.

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Molecular biology of the cell·2001

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Cdc7 kinase and its activator Dbf4 protein are conserved across eukaryotes, from yeast to humans.
  • Dbf4-related activators bind to and stimulate the kinase activity of Cdc7-like catalytic subunits.
  • The kinase activity of Cdc7 is regulated by the cell cycle, primarily through the availability of its activation subunit.

Purpose of the Study:

  • To investigate the conserved role of the Cdc7-Dbf4 kinase complex in eukaryotic cell division.
  • To understand the cell cycle regulation of Cdc7 kinase activity.
  • To identify key substrates and functions of the Cdc7-Dbf4 complex.

Main Methods:

  • Utilized genetic studies in Saccharomyces cerevisiae and fission yeast.
  • Investigated the cell cycle-dependent regulation of Dbf4 protein levels.

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  • Identified MCM2 protein as a physiological substrate.

    • Main Results:

    • Cdc7 kinase activity is regulated by the availability of the Dbf4 subunit, which increases at the G1/S boundary and remains high during S phase.
    • MCM2 protein was identified as a key substrate of the Cdc7-Dbf4 complex.
    • Genetic studies in fission yeast revealed additional roles in meiosis, DNA repair, and chromatin maintenance.

    Conclusions:

    • The Cdc7-Dbf4 kinase complex plays a crucial, conserved role in initiating DNA replication.
    • Cell cycle regulation of Dbf4 availability is critical for controlling S phase progression.
    • The complex is involved in diverse cellular processes beyond DNA replication, including meiosis and DNA repair.