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Nat Commun. 2015 Apr 21;6:6946. doi: 10.1038/ncomms7946.

Mouse oocytes depend on BubR1 for proper chromosome segregation but not for prophase I arrest.

Author information

1
Sorbonne Universités, UPMC Université Paris 06, Institut de Biologie Paris Seine (IBPS), UMR7622, 75005 Paris, France.
2
CNRS, IBPS, UMR7622 Developmental Biology Lab, 75005 Paris, France.
3
Departement de Biologie du Développement et Cellules Souches, CNRS URA2578, Unité de Régulation Epigénétique, Institut Pasteur, 75015 Paris, France.
4
Department of Pediatric and Adolescent Medicine and Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.

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.

PMID:
25897860
PMCID:
PMC4439927
DOI:
10.1038/ncomms7946
[Indexed for MEDLINE]
Free PMC Article

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