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Centrosome age regulates kinetochore microtubule stability and biases chromosome mis-segregation

  1. Ivana Gasic
  2. Purnima Nerurkar
  3. Patrick Meraldi  Is a corresponding author
  1. University of Geneva, Switzerland
  2. Eidgenössische Technische Hochschule Zürich, Switzerland
Research Article
  • Cited 20
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Cite this article as: eLife 2015;4:e07909 doi: 10.7554/eLife.07909

Abstract

The poles of the mitotic spindle contain one old and one young centrosome. In asymmetric stem cell divisions, the age of centrosomes affects their behaviour and their probability to remain in the stem cell. In contrast, in symmetric divisions old and young centrosomes are thought to behave equally. This hypothesis is, however, untested. Here, we show in symmetrically dividing human cells, that kinetochore-microtubules associated to old centrosomes are more stable than those associated to young centrosomes, and that this difference favors the accumulation of premature end-on attachments that delay the alignment of polar chromosomes at the old centrosome. This differential microtubule stability depends on cenexin, a protein enriched on old centrosomes. It persists throughout mitosis, biasing chromosome segregation in anaphase by causing daughter cells with old centrosomes to retain non-disjoint chromosomes 85% of the time. We conclude that centrosome age imposes via cenexin a functional asymmetry on all mitotic spindles.

Article and author information

Author details

  1. Ivana Gasic

    Department of Cellular Physiology and Metabolism, University of Geneva, Geneva, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  2. Purnima Nerurkar

    Institute of Biochemistry, Eidgenössische Technische Hochschule Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Patrick Meraldi

    Department of Cellular Physiology and Metabolism, University of Geneva, Geneva, Switzerland
    For correspondence
    Patrick.meraldi@unige.ch
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Anna Akhmanova, Utrecht University, Netherlands

Publication history

  1. Received: April 2, 2015
  2. Accepted: August 18, 2015
  3. Accepted Manuscript published: August 19, 2015 (version 1)
  4. Version of Record published: September 23, 2015 (version 2)

Copyright

© 2015, Gasic et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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