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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 ISSN 0021-9525.
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Official URL: http://dx.doi.org/10.1083/jcb.201607096
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 | ||||||||||||||||||
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Subjects: | Q Science > QH Natural history | ||||||||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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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: |
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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 | ||||||||||||||||||
Date of first compliant deposit: | 9 August 2017 | ||||||||||||||||||
Date of first compliant Open Access: | 11 November 2017 | ||||||||||||||||||
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) | ||||||||||||||||||
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