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Publication : The cohesin release factor Wapl interacts with Bub3 to govern SAC activity in female meiosis I.

First Author  Zhou C Year  2020
Journal  Sci Adv Volume  6
Issue  15 Pages  eaax3969
PubMed ID  32284991 Mgi Jnum  J:326154
Mgi Id  MGI:7287933 Doi  10.1126/sciadv.aax3969
Citation  Zhou C, et al. (2020) The cohesin release factor Wapl interacts with Bub3 to govern SAC activity in female meiosis I. Sci Adv 6(15):eaax3969
abstractText  During mitotic prophase, cohesins are removed from chromosome arms by Wapl to ensure faithful sister chromatid separation. However, during female meiosis I, the resolution of chiasmata requires the proteolytic cleavage of cohesin subunit Rec8 along chromosome arms by Separase to separate homologs, and thus the role of Wapl remained unknown. Here, we report that Wapl functions as a regulator of spindle assembly checkpoint (SAC) to prevent aneuploidy in meiosis I. Depletion of Wapl accelerates meiotic progression, inactivates SAC, and causes meiotic defects such as aberrant spindle/chromosome structure and incorrect kinetochore-microtubule (K-MT) attachment, consequently leading to aneuploid eggs. Notably, we identify Bub3 as a binding partner of Wapl by immunoprecipitation and mass spectrometry analysis. We further determine that Wapl controls the SAC activity by maintaining Bub3 protein level and document that exogenous Bub3 restores the normal meiosis in Wapl-depleted oocytes. Together, our findings uncover unique, noncanonical roles for Wapl in mediating control of the SAC in female meiosis I.
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