El Yakoubi Warif, Buffin Eulalie, Cladière Damien, Gryaznova Yulia, Berenguer Inés, Touati Sandra A, Gómez Rocío, Suja José A, van Deursen Jan M, Wassmann Katja
Sorbonne Universités, UPMC Univ. Paris 06, Institut de Biologie Paris Seine (IBPS), UMR7622, Paris, 75005, France.
CNRS, IBPS, UMR7622 Developmental Biology Lab, Paris, 75005, France.
Nat Commun. 2017 Sep 25;8(1):694. doi: 10.1038/s41467-017-00774-3.
A key feature of meiosis is the step-wise removal of cohesin, the protein complex holding sister chromatids together, first from arms in meiosis I and then from the centromere region in meiosis II. Centromeric cohesin is protected by Sgo2 from Separase-mediated cleavage, in order to maintain sister chromatids together until their separation in meiosis II. Failures in step-wise cohesin removal result in aneuploid gametes, preventing the generation of healthy embryos. Here, we report that kinase activities of Bub1 and Mps1 are required for Sgo2 localisation to the centromere region. Mps1 inhibitor-treated oocytes are defective in centromeric cohesin protection, whereas oocytes devoid of Bub1 kinase activity, which cannot phosphorylate H2A at T121, are not perturbed in cohesin protection as long as Mps1 is functional. Mps1 and Bub1 kinase activities localise Sgo2 in meiosis I preferentially to the centromere and pericentromere respectively, indicating that Sgo2 at the centromere is required for protection.In meiosis I centromeric cohesin is protected by Sgo2 from Separase-mediated cleavage ensuring that sister chromatids are kept together until their separation in meiosis II. Here the authors demonstrate that Bub1 and Mps1 kinase activities are required for Sgo2 localisation to the centromere region.
减数分裂的一个关键特征是逐步去除黏连蛋白,即一种将姐妹染色单体维系在一起的蛋白质复合体,先是在减数分裂I中从染色体臂上去除,然后在减数分裂II中从着丝粒区域去除。着丝粒黏连蛋白受到Sgo2的保护,免受分离酶介导的切割,以便在减数分裂II中姐妹染色单体分离之前保持在一起。逐步去除黏连蛋白的过程出现故障会导致非整倍体配子的产生,从而阻碍健康胚胎的形成。在此,我们报告Bub1和Mps1的激酶活性是Sgo2定位于着丝粒区域所必需的。用Mps1抑制剂处理的卵母细胞在着丝粒黏连蛋白保护方面存在缺陷,而缺乏Bub1激酶活性、无法在T121位点磷酸化H2A的卵母细胞,只要Mps1功能正常,其黏连蛋白保护就不会受到干扰。Mps1和Bub1的激酶活性在减数分裂I中分别优先将Sgo2定位于着丝粒和着丝粒周围,这表明着丝粒处的Sgo2是保护所必需的。在减数分裂I中,着丝粒黏连蛋白受到Sgo2的保护,免受分离酶介导的切割,确保姐妹染色单体在减数分裂II分离之前保持在一起。在此,作者证明Bub1和Mps1的激酶活性是Sgo2定位于着丝粒区域所必需的。