The kinetochore prevents centromere-proximal crossover recombination during meiosis

Nadine Vincenten, Lisa Marie Kuhl, Isabel Lam, Ashwini Oke, Alastair R W Kerr, Andreas Hochwagen, Jennifer Fung, Scott Keeney, Gerben Vader, Adèle L. Marston

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere10850
JournaleLife
Volume4
Issue numberDECEMBER2015
DOIs
StatePublished - Dec 14 2015

Fingerprint

Kinetochores
Centromere
Meiosis
Chromosomes
Genetic Recombination
Chromosome Segregation
DNA Breaks
Aneuploidy
Saccharomycetales
DNA
Down Syndrome
Germ Cells
Refractory materials
Yeast
Genes
Genome
Incidence

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

Vincenten, N., Kuhl, L. M., Lam, I., Oke, A., Kerr, A. R. W., Hochwagen, A., ... Marston, A. L. (2015). The kinetochore prevents centromere-proximal crossover recombination during meiosis. eLife, 4(DECEMBER2015), [e10850]. https://doi.org/10.7554/eLife.10850

The kinetochore prevents centromere-proximal crossover recombination during meiosis. / Vincenten, Nadine; Kuhl, Lisa Marie; Lam, Isabel; Oke, Ashwini; Kerr, Alastair R W; Hochwagen, Andreas; Fung, Jennifer; Keeney, Scott; Vader, Gerben; Marston, Adèle L.

In: eLife, Vol. 4, No. DECEMBER2015, e10850, 14.12.2015.

Research output: Contribution to journalArticle

Vincenten, N, Kuhl, LM, Lam, I, Oke, A, Kerr, ARW, Hochwagen, A, Fung, J, Keeney, S, Vader, G & Marston, AL 2015, 'The kinetochore prevents centromere-proximal crossover recombination during meiosis', eLife, vol. 4, no. DECEMBER2015, e10850. https://doi.org/10.7554/eLife.10850
Vincenten N, Kuhl LM, Lam I, Oke A, Kerr ARW, Hochwagen A et al. The kinetochore prevents centromere-proximal crossover recombination during meiosis. eLife. 2015 Dec 14;4(DECEMBER2015). e10850. https://doi.org/10.7554/eLife.10850
Vincenten, Nadine ; Kuhl, Lisa Marie ; Lam, Isabel ; Oke, Ashwini ; Kerr, Alastair R W ; Hochwagen, Andreas ; Fung, Jennifer ; Keeney, Scott ; Vader, Gerben ; Marston, Adèle L. / The kinetochore prevents centromere-proximal crossover recombination during meiosis. In: eLife. 2015 ; Vol. 4, No. DECEMBER2015.
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