期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-04427-x
关键词
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资金
- SNF-project grant [31003A_160006]
- Basilea Pharmaceutica International Ltd
- University of Geneva
- Wellcome Investigator Award [106151/Z/14/Z]
- Royal Society Wolfson Research Merit Award [WM150020]
- short-term EMBO fellowship [ASTF 178-2016]
- Wellcome Trust [106151/Z/14/Z] Funding Source: Wellcome Trust
- Swiss National Science Foundation (SNF) [31003A_160006] Funding Source: Swiss National Science Foundation (SNF)
Kinetochores are multi-protein complexes that power chromosome movements by tracking microtubules plus-ends in the mitotic spindle. Human kinetochores bind up to 20 micro tubules, 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.
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