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Related Experiment Videos

Positive feedback sharpens the anaphase switch.

Liam J Holt1, Andrew N Krutchinsky, David O Morgan

  • 1Department of Physiology, University of California, San Francisco, California 94158, USA.

Nature
|June 17, 2008
PubMed
Summary
This summary is machine-generated.

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The cyclin-dependent kinase 1 (Cdk1) and phosphatase Cdc14 regulate securin phosphorylation, controlling sister-chromatid cohesion during anaphase. This phosphoregulation ensures abrupt chromosome segregation through a positive feedback loop.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Anaphase onset requires abrupt sister-chromatid cohesion dissolution for simultaneous chromosome disjunction.
  • The anaphase-promoting complex (APC) initiates anaphase by degrading securin, enabling separase protease activity.
  • Regulatory mechanisms driving this rapid transition remain incompletely understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms governing the abrupt switch-like initiation of anaphase.
  • To investigate the role of cyclin-dependent kinase 1 (Cdk1) and phosphatase Cdc14 in regulating securin degradation.
  • To determine how phosphoregulation of securin impacts chromosome segregation synchrony.

Main Methods:

  • Investigated the effect of Cdk1-dependent securin phosphorylation on APC-mediated ubiquitination.

Related Experiment Videos

  • Assessed the impact of Cdc14-mediated dephosphorylation on securin ubiquitination rates.
  • Utilized mutant analysis to examine the consequences of disrupted securin phosphoregulation on chromosome segregation.

    • Main Results:

    • Cdk1 phosphorylation of securin inhibits its ubiquitination by the APC.
    • Cdc14 reverses securin phosphorylation, thereby enhancing securin ubiquitination.
    • A positive feedback loop involving separase activation of Cdc14 amplifies securin degradation and anaphase abruptness.
    • Mutations impairing securin phosphoregulation led to decreased chromosome segregation synchrony.

    Conclusions:

    • Securin phosphoregulation by Cdk1 and Cdc14 is crucial for the switch-like initiation of anaphase.
    • A positive feedback loop involving separase, Cdc14, and securin ensures rapid and synchronous sister-chromatid separation.
    • Coordination of securin degradation with Cdk1/Cdc14 activity and spindle dynamics is essential for proper chromosome segregation.