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Spindle assembly checkpoint satisfaction occurs through end-on but not lateral kinetochore-microtubule interactions under tension

View ORCID ProfileJonathan Kuhn, Sophie Dumont
doi: https://doi.org/10.1101/105460
Jonathan Kuhn
Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA, 94143Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA, 94143
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  • ORCID record for Jonathan Kuhn
Sophie Dumont
Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA, 94143Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA, 94143Department of Cell and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, 94143
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  • For correspondence: Sophie.Dumont@ucsf.edu
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Abstract

To ensure accurate chromosome segregation, the spindle assembly checkpoint (SAC) prevents anaphase until all kinetochores attach to the spindle. What signals the SAC monitors remains unclear. We do not know the contributions of different microtubule attachment features, or tension from biorientation, to SAC satisfaction in normal mitosis - or how these possible cues change during attachment. Here, we quantify concurrent Mad1 intensity, reporting on SAC silencing, and real-time attachment geometry, occupancy, and tension at individual mammalian kinetochores. We show that Mad1 loss from the kinetochore occurs in switch-like events with robust kinetics, and that metaphase-like tension across sister kinetochores is established just before Mad1 loss events at the first sister. We demonstrate that CenpE-mediated lateral attachment of the second sister can persistently generate this metaphase-like tension prior to biorientation, likely stabilizing sister end-on attachment, yet cannot induce Mad1 loss from that kinetochore. Instead, Mad1 loss begins after several end-on microtubules attach. Thus, end-on attachment provides geometry-specific molecular cues, or force on specific kinetochore linkages, that other attachment geometries cannot provide.

Summary The spindle assembly checkpoint (SAC) delays anaphase until kinetochores are properly attached to the spindle. The authors demonstrate that the SAC monitors geometry-specific molecular cues, or force on specific kinetochore linkages, that “end-on” but not “lateral” attachments generating persistent tension can provide.

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Posted February 03, 2017.
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Spindle assembly checkpoint satisfaction occurs through end-on but not lateral kinetochore-microtubule interactions under tension
Jonathan Kuhn, Sophie Dumont
bioRxiv 105460; doi: https://doi.org/10.1101/105460
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Spindle assembly checkpoint satisfaction occurs through end-on but not lateral kinetochore-microtubule interactions under tension
Jonathan Kuhn, Sophie Dumont
bioRxiv 105460; doi: https://doi.org/10.1101/105460

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