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

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Auckland, Philip, Clarke, Nicholas I., Royle, Stephen J. and McAinsh, Andrew D. (2017) Congressing kinetochores progressively load Ska complexes to prevent force-dependent detachment. The Journal of Cell Biology, 216 (6). pp. 1623-1639. doi:10.1083/jcb.201607096

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Official URL: http://dx.doi.org/10.1083/jcb.201607096

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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.

Item Type: Journal Article
Subjects: Q Science > QH Natural history
Divisions: Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology
Faculty of Medicine > Warwick Medical School > Biomedical Sciences
Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Chromosomes, Spindle (Cell division)
Journal or Publication Title: The Journal of Cell Biology
Publisher: Rockefeller University Press
ISSN: 0021-9525
Official Date: 11 May 2017
Dates:
DateEvent
11 May 2017Published
13 March 2017Accepted
Volume: 216
Number: 6
Page Range: pp. 1623-1639
DOI: 10.1083/jcb.201607096
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Funder: Medical Research Council (Great Britain) (MRC), Cancer Research UK (CRUK), Wellcome Trust (London, England), Royal Society (Great Britain). Wolfson Research Merit Award (RSWRMA)
Grant number: MR/J003964/1 (MRC), C25425/A16141 (CRUK), C25425/A15182 (CRUK), 106151/Z/14/Z (WT), WM150020 (RSWRMA)
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
MR/J003964/1[MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
C25425/A16141Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
C25425/A15182Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
UNSPECIFIEDWellcome Trusthttp://dx.doi.org/10.13039/100010269
106151/Z/14/Z (WT), WM150020Royal Society (Great Britain). Wolfson Research Merit Award (RSWRMA)http://dx.doi.org/10.13039/501100000288

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