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Related Experiment Videos

Mitotic exit in two dimensions.

Attila Tóth1, Ethel Queralt, Frank Uhlmann

  • 1Molecular Network Dynamics Group of Hungarian Academy of Sciences and Budapest University of Technology and Economics, 1111 Budapest Gellert ter 4, Hungary.

Journal of Theoretical Biology
|July 31, 2007
PubMed
Summary
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Mitotic exit in budding yeast relies on two bistable switches. These switches, involving Cdc14 phosphatase and Cdk1 kinase, ensure ordered cell cycle progression and depend on separase activation for proper regulation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biophysics

Background:

  • Mitotic exit in eukaryotes requires down-regulation of cyclin-dependent kinase 1 (Cdk1) activity and dephosphorylation of its targets.
  • In budding yeast, Cdc14 protein-phosphatase release and activation are crucial for mitotic exit, controlled by FEAR and MEN networks.
  • Recent findings highlight the essential role of anaphase-promoting protease (separase) in Cdc14 activation, linking mitotic exit to anaphase completion.

Purpose of the Study:

  • To propose and explain a new model for mitotic exit in budding yeast based on the dependency of Cdc14 activation on separase.
  • To elucidate the mechanisms underlying Cdc14 activation and mitotic exit using phaseplane analysis.
  • To identify and characterize the bistable switches governing the regulatory network of mitotic exit.

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Main Methods:

  • Phaseplane analysis of the regulatory network controlling mitotic exit.
  • Modeling of bistable switches within the FEAR and MEN networks.
  • Analysis of cell cycle mutant behaviors in relation to predicted thresholds.

Main Results:

  • The model reveals two key bistable switches: one involving positive feedback between MEN, Cdc14, and Cdk1 inhibition, and another irreversible switch driven by mutual antagonism between Cdk1 and APC(Cdh1).
  • Both switches exhibit characteristic thresholds for Cdk1 and Cdc14 activity, respectively.
  • The activation of Cdc20 triggers separase activation and Cdk1 down-regulation, initiating the MEN-Cdc14 feedback loop, which subsequently activates the Cdk1-APC(Cdh1) switch.

Conclusions:

  • The proposed model explains mitotic exit in budding yeast through two ordered bistable switches.
  • These switches ensure a robust and sequential execution of mitotic exit, dependent on anaphase progression.
  • The findings provide insights into cell cycle control mechanisms and the role of specific protein activities and thresholds.