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Manipulation and Analysis of Cell Cycle-Dependent Processes in Budding Yeast
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A quantitative model for ordered Cdk substrate dephosphorylation during mitotic exit

Céline Bouchoux1, Frank Uhlmann

  • 1Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, London WC2A 3LY, UK.

Cell
|November 15, 2011
PubMed

Insights

Mitotic exit involves ordered events. In budding yeast, distinct Cdk substrate dephosphorylation timings reveal how phosphatase and kinase activities control cell cycle progression.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitotic exit follows sister chromatid separation and involves dephosphorylation of numerous substrates by cyclin-dependent kinase (Cdk).
  • The precise mechanisms governing the temporal order of these dephosphorylation events during mitotic exit remain poorly understood.

Purpose of the Study:

  • To investigate the ordered timing of Cdk substrate dephosphorylation during mitotic exit in budding yeast.
  • To elucidate the mechanisms that establish the temporal sequence of events during mitotic exit.

Main Methods:

  • In vivo experiments modulating cyclin-dependent kinase (Cdk) and Cdc14 phosphatase activities.
  • In vitro kinetic analysis of Cdk substrate phosphorylation and dephosphorylation.
  • Testing different models for the temporal ordering of mitotic exit events.

Main Results:

  • Dephosphorylation of Cdk substrates involved in sequential mitotic exit events occurs with ordered timing.
  • The phosphatase to kinase ratio gradually changes during mitotic exit.
  • Cdk substrates respond to distinct thresholds of this ratio change, leading to ordered dephosphorylation.

Conclusions:

  • The gradual shift in the phosphatase to kinase ratio provides a quantitative mechanism for ordering mitotic exit events.
  • This study offers a mechanistic explanation for a quantitative model of cell-cycle progression.
  • Findings in budding yeast provide insights into fundamental cell cycle regulation.

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