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Super-resolution kinetochore tracking reveals the mechanisms of human sister kinetochore directional switching

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Burroughs, Nigel John, Harry, Edward and McAinsh, Andrew D. (2015) Super-resolution kinetochore tracking reveals the mechanisms of human sister kinetochore directional switching. eLife, 4 . e09500. doi:10.7554/eLife.09500 ISSN 2050-084X.

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Official URL: http://dx.doi.org/10.7554/eLife.09500

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Abstract

The congression of chromosomes to the spindle equator involves the directed motility of bi-orientated sister kinetochores. Sister kinetochores bind bundles of dynamic microtubules and are physically connected through centromeric chromatin. A crucial question is to understand how sister kinetochores are coordinated to generate motility and directional switches. Here, we combine super-resolution tracking of kinetochores with automated switching-point detection to analyse sister switching dynamics over thousands of events. We discover that switching is initiated by both the leading (microtubules depolymerising) or trailing (microtubules polymerising) kinetochore. Surprisingly, trail-driven switching generates an overstretch of the chromatin that relaxes over the following half-period. This rules out the involvement of a tension sensor, the central premise of the long-standing tension-model. Instead, our data support a model in which clocks set the intrinsic-switching time of the two kinetochore-attached microtubule fibres, with the centromeric spring tension operating as a feedback to slow or accelerate the clocks.

Item Type: Journal Article
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
Library of Congress Subject Headings (LCSH): Spindle (Cell division), Microtubules, Chromatin, Centromere, Chromosomes
Journal or Publication Title: eLife
Publisher: eLife Sciences Publications Ltd.
ISSN: 2050-084X
Official Date: 13 October 2015
Dates:
DateEvent
13 October 2015Published
13 October 2015Accepted
18 June 2015Submitted
Volume: 4
Article Number: e09500
DOI: 10.7554/eLife.09500
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Funder: Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Wellcome Trust (London, England)
Grant number: BB/I021353/1 (BBSRC) 106151/Z/14/Z (Wellcome Trust)

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