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Defining pathways of spindle checkpoint silencing: functional redundancy between Cdc20 ubiquitination and p31(comet)

Luying Jia1, Bing Li, Ross T Warrington

  • 1Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Molecular Biology of the Cell
|September 23, 2011
PubMed

Insights

The spindle checkpoint ensures proper chromosome attachment during cell division. This study reveals p31(comet) and Cdc20 ubiquitination are key, redundant mechanisms that dismantle the mitotic checkpoint complex, allowing cell division to proceed.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • The spindle checkpoint prevents aneuploidy by inhibiting the anaphase-promoting complex/cyclosome (APC/C).
  • The mitotic checkpoint complex (MCC), comprising BubR1, Bub3, Mad2, and Cdc20, is crucial for this inhibition.
  • Checkpoint inactivation and MCC disassembly at the metaphase-anaphase transition are poorly understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying spindle checkpoint inactivation.
  • To investigate the role of Cdc20 autoubiquitination in MCC disassembly.
  • To identify factors involved in the dissociation of Mad2 from Cdc20.

Main Methods:

  • Depletion of p31(comet) using RNA interference.
  • Analysis of Mad2 and Cdc20 interactions using nonubiquitinatable Cdc20 mutants.
  • Observation of Mad2 dissociation from Cdc20 during checkpoint inactivation.

Main Results:

  • Depleting p31(comet) delayed Mad2 dissociation from Cdc20 mutants unable to autoubiquitinate.
  • Cdc20 autoubiquitination promotes Mad2 dissociation from Cdc20.
  • p31(comet) also plays a critical role in promoting Mad2 dissociation from Cdc20.

Conclusions:

  • Both p31(comet) and Cdc20 ubiquitination are essential and redundant mechanisms for spindle checkpoint inactivation.
  • These processes work together to promote Mad2 dissociation from Cdc20, facilitating anaphase onset.

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