title: Mouse oocytes depend on BubR1 for proper chromosome segregation but not for prophase I arrest.
abstract: Mammalian female meiosis is error prone, with rates of meiotic chromosome missegregations strongly increasing towards the end of the reproductive lifespan. A strong reduction of BubR1 has been observed in oocytes of women approaching menopause and in ovaries of aged mice, which led to the hypothesis that a gradual decline of BubR1 contributes to age-related aneuploidization. Here we employ a conditional knockout approach in mouse oocytes to dissect the meiotic roles of BubR1. We show that BubR1 is required for diverse meiotic functions, including persistent spindle assembly checkpoint activity, timing of meiosis I and the establishment of robust kinetochore-microtubule attachments in a meiosis-specific manner, but not prophase I arrest. These data reveal that BubR1 plays a multifaceted role in chromosome segregation during the first meiotic division and suggest that age-related decline of BubR1 is a key determinant of the formation of aneuploid oocytes as women approach menopause.
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, Institut de Biologie Paris Seine (IBPS), UMR7622, 75005 Paris, France.|CNRS, IBPS, UMR7622 Developmental Biology Lab, 75005 Paris, France.
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Touati
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, Institut de Biologie Paris Seine (IBPS), UMR7622, 75005 Paris, France.|CNRS, IBPS, UMR7622 Developmental Biology Lab, 75005 Paris, France.
authors.forename: Eulalie
authors.initials: E
authors.lastname: Buffin
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, Institut de Biologie Paris Seine (IBPS), UMR7622, 75005 Paris, France.|CNRS, IBPS, UMR7622 Developmental Biology Lab, 75005 Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Cladière
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, Institut de Biologie Paris Seine (IBPS), UMR7622, 75005 Paris, France.|CNRS, IBPS, UMR7622 Developmental Biology Lab, 75005 Paris, France.
authors.forename: Khaled
authors.initials: K
authors.lastname: Hached
authors.affiliation: Departement de Biologie du Développement et Cellules Souches, CNRS URA2578, Unité de Régulation Epigénétique, Institut Pasteur, 75015 Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Rachez
authors.affiliation: Department of Pediatric and Adolescent Medicine and Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
authors.forename: Jan M
authors.initials: JM
authors.lastname: van Deursen
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, Institut de Biologie Paris Seine (IBPS), UMR7622, 75005 Paris, France.|CNRS, IBPS, UMR7622 Developmental Biology Lab, 75005 Paris, France.
authors.forename: Katja
authors.initials: K
authors.lastname: Wassmann
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation / Q000502:physiology*; D005260:Female; D017907:Leviviridae; D049469:Meiotic Prophase I / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D009865:Oocytes / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C584278:Bub1b protein, mouse; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases