@article{da364915946848b6ac3f287ac74ad155,
title = "The kinetochore prevents centromere-proximal crossover recombination during meiosis",
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.",
author = "Nadine Vincenten and Kuhl, {Lisa Marie} and Isabel Lam and Ashwini Oke and Kerr, {Alastair R.W.} and Andreas Hochwagen and Jennifer Fung and Scott Keeney and Gerben Vader and Marston, {Ad{\`e}le L.}",
note = "Funding Information: This work was supported by the Wellcome Trust [090903], [092076] and [089396] (AM, NV and AK), a fellowship from the Netherlands Organisation for Scientific Research (NWO Veni-016.111.004) (GV), NIH/NIGMS grant R01 GM088248 (AH), NIH grant R01 GM097213 (JCF) and by the US National Institutes of Health grant R01-GM058673 (SK). The laboratory of GV is supported by a grant from the European Research Council (ERC StG 638197 {"}URDNA{"}). We are grateful to Bianka Baying at Genecore EMBL for library preparation and sequencing; Agnes Viale and the MSKCC Integrated Genomics Operation for sequencing Spo11 oligos; Nick Socci at the MSKCC Bioinformatics Core for mapping Spo11 oligos; Stewart Shuman (MSKCC) for gifts of T4 RNA ligase. We thank Julie Blyth for help with strain construction. GV acknowledges Gerry Fink for support during the initiation of this study. We thank Elizabeth Bayne, Puck Knipscheer, David Leach, Nuno Martins, Andrea Musacchio, Alex Bird, Arnaud Rondelet and John Weir for comments on the manuscript. Funding Information: This work was supported by the Wellcome Trust [090903], [092076] and [089396] (AM, NV and AK), a fellowship from the Netherlands Organisation for Scientific Research (NWO Veni-016.111.004) (GV), NIH/NIGMS grant R01 GM088248 (AH), NIH grant R01 GM097213 (JCF) and by the US National Institutes of Health grant R01-GM058673 (SK). The laboratory of GV is supported by a grant from the European Research Council (ERC StG 638197 {"}URDNA{"}). We are grateful to Bianka Baying at Genecore EMBL for library preparation and sequencing; Agnes Viale and the MSKCC Inte-grated Genomics Operation for sequencing Spo11 oligos; Nick Socci at the MSKCC Bioinformatics Core for mapping Spo11 oligos; Stewart Shuman (MSKCC) for gifts of T4 RNA ligase. We thank Julie Blyth for help with strain construction. GV acknowledges Gerry Fink for support during the initiation of this study. We thank Elizabeth Bayne, Puck Knipscheer, David Leach, Nuno Martins, Andrea Musacchio, Alex Bird, Arnaud Rondelet and John Weir for comments on the manuscript. Publisher Copyright: {\textcopyright} Vincenten et al.",
year = "2015",
month = dec,
day = "14",
doi = "10.7554/eLife.10850",
language = "English (US)",
volume = "4",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
number = "DECEMBER2015",
}