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Studying Mitotic Checkpoint by Illustrating Dynamic Kinetochore Protein Behavior and Chromosome Motion in Living Drosophila Syncytial Embryos
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A cyclin-dependent kinase inhibitor, Dacapo, is necessary for timely exit from the cell cycle during Drosophila

J C de Nooij1, M A Letendre, I K Hariharan

  • 1Massachusetts General Hospital Cancer Center, Charlestown 02129, USA.

Cell
|December 27, 1996
PubMed

Insights

Dacapo (dap), a novel cdk inhibitor, is crucial for embryonic development by regulating cell cycle exit. Overexpression disrupts cell cycles, while mutations delay this exit, impacting cell quiescence.

Area of Science:

  • Developmental Biology
  • Cell Cycle Regulation
  • Molecular Genetics

Background:

  • The Rap1 GTPase pathway is involved in various cellular processes.
  • Cyclin-dependent kinase (cdk) inhibitors regulate cell cycle progression.
  • Mammalian cdk inhibitors have diverse roles, but their essentiality in development is not fully understood.

Purpose of the Study:

  • To identify genes interacting with Rap1 GTPase.
  • To characterize the function of a novel Drosophila gene, dacapo (dap).
  • To elucidate the role of dap in embryonic development and cell cycle control.

Main Methods:

  • Genetic screening in Drosophila to identify interacting genes.
  • In vitro assays to assess dacapo's inhibitory activity on cyclin-cdk.
  • Overexpression studies in Drosophila eye development.
  • Genetic interaction studies with retinoblastoma homolog (Rbf) and cyclin E.
  • Analysis of dap expression patterns during embryogenesis.
  • Examination of cell cycle progression and quiescence in dap mutant embryos.

Main Results:

  • Identified dacapo (dap) as a Drosophila gene interacting with Rap1 GTPase.
  • Dacapo belongs to the p21/p27 family of cdk inhibitors.
  • Dap is essential for normal Drosophila embryonic development.
  • Dacapo inhibits cyclin-cdk activity in vitro.
  • Overexpression of dap in eye development disrupts cell cycle progression and shows genetic interactions with Rbf and cyclin E.
  • Dap expression correlates with cell cycle exit during embryogenesis.
  • Dap mutant embryos exhibit delayed cell cycle exit, leading to extra cell cycles and subsequent quiescence.

Conclusions:

  • Dacapo is a critical regulator of cell cycle exit during Drosophila embryogenesis.
  • Its function is essential for achieving a precisely timed exit from the cell cycle.
  • Dacapo represents a key developmental control point, distinct from previously studied mammalian cdk inhibitors.

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