The kinetochore prevents centromere-proximal crossover recombination during meiosis
- The University of Edinburgh, United Kingdom
- Max Planck Institute of Molecular Physiology, Germany
- Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, United States
- University of California, San Francisco, United States
- 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
Reviewing Editor
- Michael Lichten, Center for Cancer Research National Cancer Institute, United States
Version history
- Received: August 13, 2015
- Accepted: December 13, 2015
- Accepted Manuscript published: December 14, 2015 (version 1)
- Version of Record published: January 28, 2016 (version 2)
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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The kinetochore prevents centromere-proximal crossover recombination during meiosis
eLife 4:e10850.
https://doi.org/10.7554/eLife.10850
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