2. Academic Validation
  3. Complete microtubule-kinetochore occupancy favours the segregation of merotelic attachments

Complete microtubule-kinetochore occupancy favours the segregation of merotelic attachments

  • Nat Commun. 2018 May 23;9(1):2042. doi: 10.1038/s41467-018-04427-x.
Damian Dudka 1,  Anna Noatynska 1,  Chris A Smith 2 3,  Nicolas Liaudet 4,  Andrew D McAinsh 2,  Patrick Meraldi 5 6
Affiliations

Affiliations

  • 1 Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211, Geneva 4, Switzerland.
  • 2 Centre for Mechanochemical Cell Biology & Division of Biomedical Sciences, Warwick Medical School, University of Warwick, CV4 7AL, Coventry, UK.
  • 3 Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK.
  • 4 Bioimaging Facility, Faculty of Medicine, University of Geneva, 1211, Geneva 4, Switzerland.
  • 5 Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211, Geneva 4, Switzerland. patrick.meraldi@unige.ch.
  • 6 Translational Research Centre in Onco-hematology, Faculty of Medicine, University of Geneva, 1211, Geneva 4, Switzerland. patrick.meraldi@unige.ch.
PMID: 29795284 DOI: 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.

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