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

Jing Chen and Jian Liu ()
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Jing Chen: National Heart, Lung and Blood Institute, National Institutes of Health
Jian Liu: National Heart, Lung and Blood Institute, National Institutes of Health

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: 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.

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5795

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DOI: 10.1038/ncomms5795

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