1. Cell Biology
Download icon

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 18
  • Views 2,314
  • Annotations
Cite this article as: eLife 2015;4:e07909 doi: 10.7554/eLife.07909


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
    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)


© 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.


  • 2,314
    Page views
  • 611
  • 18

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

  1. Further reading

Further reading

    1. Cell Biology
    2. Developmental Biology
    Amrutha Kizhedathu et al.
    Research Advance Updated

    Larval tracheae of Drosophila harbour progenitors of the adult tracheal system (tracheoblasts). Thoracic tracheoblasts are arrested in the G2 phase of the cell cycle in an ATR (mei-41)-Checkpoint Kinase1 (grapes, Chk1) dependent manner prior to mitotic re-entry. Here we investigate developmental regulation of Chk1 activation. We report that Wnt signaling is high in tracheoblasts and this is necessary for high levels of activated (phosphorylated) Chk1. We find that canonical Wnt signaling facilitates this by transcriptional upregulation of Chk1 expression in cells that have ATR kinase activity. Wnt signaling is dependent on four Wnts (Wg, Wnt5, 6,10) that are expressed at high levels in arrested tracheoblasts and are downregulated at mitotic re-entry. Interestingly, none of the Wnts are dispensable and act synergistically to induce Chk1. Finally, we show that downregulation of Wnt signaling and Chk1 expression leads to mitotic re-entry and the concomitant upregulation of Dpp signaling, driving tracheoblast proliferation.

    1. Cell Biology
    2. Neuroscience
    Sean L Johnson et al.
    Research Article

    Spinocerebellar ataxia type 3 (SCA3) belongs to the family of polyglutamine neurodegenerations. Each disorder stems from the abnormal lengthening of a glutamine repeat in a different protein. Although caused by a similar mutation, polyglutamine disorders are distinct, implicating non-polyglutamine regions of disease proteins as regulators of pathogenesis. SCA3 is caused by polyglutamine expansion in ataxin-3. To determine the role of ataxin-3’s non-polyglutamine domains in disease, we utilized a new, allelic series of Drosophila melanogaster. We found that ataxin-3 pathogenicity is saliently controlled by polyglutamine-adjacent ubiquitin-interacting motifs (UIMs) that enhance aggregation and toxicity. UIMs function by interacting with the heat shock protein, Hsc70-4, whose reduction diminishes ataxin-3 toxicity in a UIM-dependent manner. Hsc70-4 also enhances pathogenicity of other polyglutamine proteins. Our studies provide a unique insight into the impact of ataxin-3 domains in SCA3, identify Hsc70-4 as a SCA3 enhancer, and indicate pleiotropic effects from HSP70 chaperones, which are generally thought to suppress polyglutamine degeneration.