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.
authors.affiliation: The Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Nadine
authors.initials: N
authors.lastname: Vincenten
authors.affiliation: Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Lisa-Marie
authors.initials: LM
authors.lastname: Kuhl
authors.affiliation: Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Isabel
authors.initials: I
authors.lastname: Lam
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Center of Reproductive Sciences, University of California, San Francisco, San Francisco, United States.
authors.forename: Ashwini
authors.initials: A
authors.lastname: Oke
authors.affiliation: The Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Alastair Rw
authors.identifier: http://orcid.org/0000-0001-9207-6050
authors.initials: AR
authors.lastname: Kerr
authors.affiliation: Department of Biology, New York University, New York, United States.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochwagen
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Center of Reproductive Sciences, University of California, San Francisco, San Francisco, United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fung
authors.affiliation: Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Scott
authors.identifier: http://orcid.org/0000-0002-1283-6417
authors.initials: S
authors.lastname: Keeney
authors.affiliation: Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Gerben
authors.initials: G
authors.lastname: Vader
authors.affiliation: The Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Adèle L
authors.initials: AL
authors.lastname: Marston
mesh_terms: D002503:Centromere; D003434:Crossing Over, Genetic; D003598:Cytoskeletal Proteins / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism; D008540:Meiosis; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: C477822:CTF19 protein, S cerevisiae; D003598:Cytoskeletal Proteins; D029701:Saccharomyces cerevisiae Proteins
keywords: <i>s. cerevisiae</i>; DNA break formation; DNA repair; chromosome segregation; chromosomes; genes; kinetochores; meiosis; recombination