The kinetochore prevents centromere-proximal crossover recombination during meiosis
Nadine Vincenten,
Lisa-Marie Kuhl,
Isabel Lam,
Ashwini Oke,
Alastair RW Kerr,
Andreas Hochwagen,
Jennifer Fung,
Scott Keeney,
Gerben Vader,
Adèle L Marston
Affiliations
Nadine Vincenten
The Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh, United Kingdom
Lisa-Marie Kuhl
Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany
Isabel Lam
Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, United States
Ashwini Oke
Department of Obstetrics, Gynecology and Reproductive Sciences, Center of Reproductive Sciences, University of California, San Francisco, San Francisco, United States
The Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh, United Kingdom
Andreas Hochwagen
Department of Biology, New York University, New York, United States
Jennifer Fung
Department of Obstetrics, Gynecology and Reproductive Sciences, Center of Reproductive Sciences, University of California, San Francisco, San Francisco, United States
Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, United States
Gerben Vader
Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany
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
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.
