Spatial-temporal model for silencing of the mitotic spindle assembly checkpoint

Jing Chen, Jian Liu

Research output: Contribution to journalArticle

Abstract

The spindle assembly checkpoint arrests mitotic progression until each kinetochore secures a stable attachment to the spindle. Despite fluctuating noise, this checkpoint remains robust and remarkably sensitive to even a single unattached kinetochore among many attached kinetochores; moreover, the checkpoint is silenced only after the final kinetochore-spindle attachment. Experimental observations have shown that checkpoint components stream from attached kinetochores along microtubules towards spindle poles. Here we incorporate this streaming behaviour into a theoretical model that accounts for the robustness of checkpoint silencing. Poleward streams are integrated at spindle poles, but are diverted by any unattached kinetochore; consequently, accumulation of checkpoint components at spindle poles increases markedly only when every kinetochore is properly attached. This step change robustly triggers checkpoint silencing after, and only after, the final kinetochore-spindle attachment. Our model offers a conceptual framework that highlights the role of spatiotemporal regulation in mitotic spindle checkpoint signalling and fidelity of chromosome segregation.

Original languageEnglish (US)
Article number4795
JournalNature Communications
Volume5
DOIs
StatePublished - Sep 12 2014
Externally publishedYes

Fingerprint

M Phase Cell Cycle Checkpoints
Kinetochores
spindles
Poles
assembly
Spindle Poles
Chromosomes
attachment
poles
Chromosome Segregation
chromosomes
progressions
Microtubules
Noise
Theoretical Models
actuators

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Spatial-temporal model for silencing of the mitotic spindle assembly checkpoint. / Chen, Jing; Liu, Jian.

In: Nature Communications, Vol. 5, 4795, 12.09.2014.

Research output: Contribution to journalArticle

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