title: Spatial-temporal model for silencing of the mitotic spindle assembly checkpoint.
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.
authors.affiliation: National Heart, Lung and Blood Institute, National Institutes of Health, 50 South Drive, Building 50, Room 3306, Bethesda, Maryland 20892, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: National Heart, Lung and Blood Institute, National Institutes of Health, 50 South Drive, Building 50, Room 3306, Bethesda, Maryland 20892, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
mesh_terms: D001692:Biological Transport; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D020090:Chromosome Segregation; D003198:Computer Simulation; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D018386:Kinetochores / Q000737:chemistry / Q000378:metabolism; D059566:M Phase Cell Cycle Checkpoints / Q000235:genetics*; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism; D015233:Models, Statistical; D062211:Spatio-Temporal Analysis; D008941:Spindle Apparatus / Q000737:chemistry* / Q000378:metabolism; D013269:Stochastic Processes
chemical_list: D018797:Cell Cycle Proteins