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The kinetochore prevents centromere-proximal crossover recombination during meiosis

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 huma...

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Autores principales: Vincenten, Nadine, Kuhl, Lisa-Marie, Lam, Isabel, Oke, Ashwini, Kerr, Alastair RW, Hochwagen, Andreas, Fung, Jennifer, Keeney, Scott, Vader, Gerben, Marston, Adèle L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749563/
https://www.ncbi.nlm.nih.gov/pubmed/26653857
http://dx.doi.org/10.7554/eLife.10850
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author Vincenten, Nadine
Kuhl, Lisa-Marie
Lam, Isabel
Oke, Ashwini
Kerr, Alastair RW
Hochwagen, Andreas
Fung, Jennifer
Keeney, Scott
Vader, Gerben
Marston, Adèle L
author_facet Vincenten, Nadine
Kuhl, Lisa-Marie
Lam, Isabel
Oke, Ashwini
Kerr, Alastair RW
Hochwagen, Andreas
Fung, Jennifer
Keeney, Scott
Vader, Gerben
Marston, Adèle L
author_sort Vincenten, Nadine
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.10850.001
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spelling pubmed-47495632016-02-12 The kinetochore prevents centromere-proximal crossover recombination during meiosis Vincenten, Nadine Kuhl, Lisa-Marie Lam, Isabel Oke, Ashwini Kerr, Alastair RW Hochwagen, Andreas Fung, Jennifer Keeney, Scott Vader, Gerben Marston, Adèle L eLife Genes and Chromosomes 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. DOI: http://dx.doi.org/10.7554/eLife.10850.001 eLife Sciences Publications, Ltd 2015-12-14 /pmc/articles/PMC4749563/ /pubmed/26653857 http://dx.doi.org/10.7554/eLife.10850 Text en © 2015, Vincenten et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Genes and Chromosomes
Vincenten, Nadine
Kuhl, Lisa-Marie
Lam, Isabel
Oke, Ashwini
Kerr, Alastair RW
Hochwagen, Andreas
Fung, Jennifer
Keeney, Scott
Vader, Gerben
Marston, Adèle L
The kinetochore prevents centromere-proximal crossover recombination during meiosis
title The kinetochore prevents centromere-proximal crossover recombination during meiosis
title_full The kinetochore prevents centromere-proximal crossover recombination during meiosis
title_fullStr The kinetochore prevents centromere-proximal crossover recombination during meiosis
title_full_unstemmed The kinetochore prevents centromere-proximal crossover recombination during meiosis
title_short The kinetochore prevents centromere-proximal crossover recombination during meiosis
title_sort kinetochore prevents centromere-proximal crossover recombination during meiosis
topic Genes and Chromosomes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749563/
https://www.ncbi.nlm.nih.gov/pubmed/26653857
http://dx.doi.org/10.7554/eLife.10850
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