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Complete microtubule–kinetochore occupancy favours the segregation of merotelic attachments
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Dudka, Damian, Noatynska, Anna, Smith, Christopher A., Liaudet, Nicolas, McAinsh, Andrew D. and Meraldi, Patrick (2018) Complete microtubule–kinetochore occupancy favours the segregation of merotelic attachments. Nature Communications, 9 (1). doi:10.1038/s41467-018-04427-x ISSN 2041-1723.
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Official URL: http://dx.doi.org/10.1038/s41467-018-04427-x
Abstract
Kinetochores are multi-protein complexes that power chromosome movements by tracking microtubules plus-ends in the mitotic spindle. Human kinetochores bind up to 20 microtubules, even though single microtubules can generate sufficient force to move chromosomes. Here, we show that high microtubule occupancy at kinetochores ensures robust chromosome segregation by providing a strong mechanical force that favours segregation of merotelic attachments during anaphase. Using low doses of the microtubules-targeting agent BAL27862 we reduce microtubule occupancy and observe that spindle morphology is unaffected and bi-oriented kinetochores can still oscillate with normal intra-kinetochore distances. Inter-kinetochore stretching is, however, dramatically reduced. The reduction in microtubule occupancy and inter-kinetochore stretching does not delay satisfaction of the spindle assembly checkpoint or induce microtubule detachment via Aurora-B kinase, which was so far thought to release microtubules from kinetochores under low stretching. Rather, partial microtubule occupancy slows down anaphase A and increases incidences of lagging chromosomes due to merotelically attached kinetochores.
Item Type: | Journal Article | |||||||||||||||||||||
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Subjects: | Q Science > QH Natural history > QH301 Biology | |||||||||||||||||||||
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 > Clinical Trials Unit Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Microtubules, Chromosomes, Spindle (Cell division) | |||||||||||||||||||||
Journal or Publication Title: | Nature Communications | |||||||||||||||||||||
Publisher: | Nature Publishing Group | |||||||||||||||||||||
ISSN: | 2041-1723 | |||||||||||||||||||||
Official Date: | 23 May 2018 | |||||||||||||||||||||
Dates: |
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Volume: | 9 | |||||||||||||||||||||
Number: | 1 | |||||||||||||||||||||
DOI: | 10.1038/s41467-018-04427-x | |||||||||||||||||||||
Status: | Peer Reviewed | |||||||||||||||||||||
Publication Status: | Published | |||||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||||||||
Date of first compliant deposit: | 29 May 2018 | |||||||||||||||||||||
Date of first compliant Open Access: | 1 June 2018 | |||||||||||||||||||||
RIOXX Funder/Project Grant: |
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