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Cells Escape an Operational Mitotic Checkpoint through a Stochastic Process.

Paolo Bonaiuti1, Elena Chiroli1, Fridolin Gross1

  • 1Istituto Firc di Oncologia Molecolare, IFOM, via Adamello 16, 20139 Milan, Italy.

Current Biology : CB
|December 19, 2017
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Summary
This summary is machine-generated.

Yeast cells adapt to mitotic checkpoint arrest, resuming proliferation. This adaptation occurs while the checkpoint remains active, driven by random fluctuations in APC/CCdc20.

Keywords:
adaptationmathematical modelsmitotic checkpointmolecular network dynamicsspindle assembly checkpoint

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Area of Science:

  • Cell biology
  • Molecular biology
  • Genetics

Background:

  • The mitotic checkpoint prevents cell division with improperly attached chromosomes.
  • Cells can adapt and resume proliferation after a prolonged arrest.
  • The mechanism and uniformity of adaptation are not fully understood.

Purpose of the Study:

  • To investigate whether the mitotic checkpoint remains active during adaptation.
  • To determine if all cells in a population adapt equally.
  • To elucidate the molecular drivers of adaptation to mitotic arrest.

Main Methods:

  • Utilized yeast as a model organism.
  • Quantitatively analyzed cell cycle progression and mitotic checkpoint activity.
  • Investigated the role of APC/CCdc20 fluctuations.

Main Results:

  • The mitotic checkpoint remains operational during adaptation in yeast cells.
  • All cells within a genetically homogeneous population exhibit similar adaptation propensities.
  • Adaptation is consistent with a model involving random fluctuations of APC/CCdc20.

Conclusions:

  • Mitotic checkpoint adaptation is an active process where the checkpoint remains functional.
  • Random fluctuations in APC/CCdc20 drive adaptation, allowing cells to overcome sustained arrest.
  • Provides a quantitative model for understanding cell cycle progression under constant inhibitory stimuli.