The kinetochore prevents centromere-proximal crossover recombination during meiosis

  1. Nadine Vincenten
  2. Lisa-Marie Kuhl
  3. Isabel Lam
  4. Ashwini Oke
  5. Alastair RW Kerr
  6. Andreas Hochwagen
  7. Jennifer Fung
  8. Scott Keeney
  9. Gerben Vader
  10. Adèle L Marston  Is a corresponding author
  1. The University of Edinburgh, United Kingdom
  2. Max Planck Institute of Molecular Physiology, Germany
  3. Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, United States
  4. University of California, San Francisco, United States
  5. New York University, United States

Abstract

During meiosis, crossover recombination is essential to link homologous chromosomes and drive faithful chromosome segregation. Crossover recombination is non-random across the genome, and centromere-proximal crossovers are associated with an increased risk of aneuploidy, including Trisomy 21 in humans. Here, we identify the conserved Ctf19/CCAN kinetochore sub-complex as a major factor that minimizes potentially deleterious centromere-proximal crossovers in budding yeast. We uncover multi-layered suppression of pericentromeric recombination by the Ctf19 complex, operating across distinct chromosomal distances. The Ctf19 complex prevents meiotic DNA break formation, the initiating event of recombination, proximal to the centromere. The Ctf19 complex independently drives the enrichment of cohesin throughout the broader pericentromere to suppress crossovers, but not DNA breaks. This non-canonical role of the kinetochore in defining a chromosome domain that is refractory to crossovers adds a new layer of functionality by which the kinetochore prevents the incidence of chromosome segregation errors that generate aneuploid gametes.

Article and author information

Author details

  1. Nadine Vincenten

    The Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Lisa-Marie Kuhl

    Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Isabel Lam

    Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Ashwini Oke

    Department of Obstetrics, Gynecology and Reproductive Sciences, Center of Reproductive Sciences, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Alastair RW Kerr

    The Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Andreas Hochwagen

    Department of Biology, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Jennifer Fung

    Department of Obstetrics, Gynecology and Reproductive Sciences, Center of Reproductive Sciences, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Scott Keeney

    Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Gerben Vader

    Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Adèle L Marston

    The Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    adele.marston@ed.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Copyright

© 2015, Vincenten 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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  1. Nadine Vincenten
  2. Lisa-Marie Kuhl
  3. Isabel Lam
  4. Ashwini Oke
  5. Alastair RW Kerr
  6. Andreas Hochwagen
  7. Jennifer Fung
  8. Scott Keeney
  9. Gerben Vader
  10. Adèle L Marston
(2015)
The kinetochore prevents centromere-proximal crossover recombination during meiosis
eLife 4:e10850.
https://doi.org/10.7554/eLife.10850

Share this article

https://doi.org/10.7554/eLife.10850

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