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J Cell Biol. 2017 Jun 5;216(6):1623-1639. doi: 10.1083/jcb.201607096. Epub 2017 May 11.

Congressing kinetochores progressively load Ska complexes to prevent force-dependent detachment.

Author information

1
Centre for Mechanochemical Cell Biology, Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, England, UK.
2
Centre for Mechanochemical Cell Biology, Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, England, UK a.d.mcainsh@warwick.ac.uk.

Abstract

Kinetochores mediate chromosome congression by either sliding along the lattice of spindle microtubules or forming end-on attachments to their depolymerizing plus-ends. By following the fates of individual kinetochores as they congress in live cells, we reveal that the Ska complex is required for a distinct substep of the depolymerization-coupled pulling mechanism. Ska depletion increases the frequency of naturally occurring, force-dependent P kinetochore detachment events, while being dispensable for the initial biorientation and movement of chromosomes. In unperturbed cells, these release events are followed by reattachment and successful congression, whereas in Ska-depleted cells, detached kinetochores remain in a futile reattachment/detachment cycle that prevents congression. We further find that Ska is progressively loaded onto bioriented kinetochore pairs as they congress. We thus propose a model in which kinetochores mature through Ska complex recruitment and that this is required for improved load-bearing capacity and silencing of the spindle assembly checkpoint.

PMID:
28495837
PMCID:
PMC5461014
DOI:
10.1083/jcb.201607096
[Indexed for MEDLINE]
Free PMC Article

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