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Spatiotemporal Analysis of Cytokinetic Events in Fission Yeast
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Spatiotemporal Analysis of Cytokinetic Events in Fission Yeast

Published on: February 20, 2017

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Identification of a Sgo2-Dependent but Mad2-Independent Pathway Controlling Anaphase Onset in Fission Yeast

John C Meadows1, Theresa C Lancaster2, Graham J Buttrick2

  • 1Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK; Institute of Advanced Study, University of Warwick, Coventry CV4 7AL, UK.

Cell Reports
|February 9, 2017
PubMed

Insights

The anaphase-promoting complex/cyclosome (APC/C) is activated after silencing the spindle assembly checkpoint (SAC). CPC interaction with Klp9 terminates a distinct APC/C-inhibitory pathway, ensuring timely cell cycle progression.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • The anaphase-promoting complex/cyclosome (APC/C) controls cell cycle progression by targeting proteins for degradation.
  • Activation of the APC/C is tightly regulated by the spindle assembly checkpoint (SAC).
  • The chromosome passenger complex (CPC) relocalizes during mitosis, playing roles in chromosome segregation.

Purpose of the Study:

  • To investigate the mechanism by which CPC interaction with Klp9 regulates APC/C activation.
  • To determine the role of Sgo2 and SAC components in this regulatory pathway.
  • To elucidate a novel APC/C-inhibitory pathway distinct from the canonical SAC.

Main Methods:

  • Fission yeast as a model organism.
  • Genetic analysis of SAC components and CPC-Klp9 interaction.
  • Biochemical assays to assess APC/C activation and protein interactions.

Main Results:

  • Disruption of CPC-Klp9 interaction delays APC/C activation.
  • This delay requires Sgo2 and specific SAC components (Bub1, Mph1/Mps1, Mad3), but not Mad1 or Mad2.
  • A specific KEN box in Mad3 is crucial for this APC/C inhibition.
  • The identified pathway is Mad2-independent, distinguishing it from the canonical SAC.

Conclusions:

  • CPC interaction with Klp9 is essential for timely APC/C activation.
  • A novel Sgo2-dependent, Mad2-independent pathway inhibits APC/C.
  • This pathway utilizes specific SAC components and is distinct from the canonical SAC, highlighting complex regulatory mechanisms in cell cycle control.
Keywords:
Mad2anaphasefission yeastkinesinmicrotubulemidzoneshugoshinspindle checkpoint

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