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.

在有丝分裂前期，通过Wapl从染色体臂上去除粘着蛋白，以确保忠实的姐妹染色单体分离。但是，在雌性减数分裂I期间，要想消除Chiasmata，需要通过Separase沿着染色体臂对粘附蛋白亚基Rec8进行蛋白水解切割，以分离同系物，因此Wapl的作用仍然未知。在这里，我们报道Wapl充当纺锤体装配检查点（SAC）的调节剂，以防止减数分裂I中的非整倍性。Wapl的消耗会加速减数分裂进程，使SAC失活，并导致减数分裂缺陷，例如异常的纺锤体/染色体结构和不正确的动粒-微管（K-MT）附着，因此导致非整倍体卵。值得注意的是，通过免疫沉淀和质谱分析，我们确定Bub3是Wapl的结合伴侣。我们进一步确定Wapl通过维持Bub3蛋白水平来控制SAC活性，并证明外源Bub3恢复了Wapl耗尽的卵母细胞中的正常减数分裂。总之，我们的发现揭示了Wapl在介导女性减数分裂I中SAC调控中的独特，非经典作用。