Institut de Biologie Paris Seine, Sorbonne Université, Paris, France.
CNRS UMR7622 Developmental Biology Lab, Sorbonne Université, Paris, France.
EMBO J. 2021 Apr 1;40(7):e106797. doi: 10.15252/embj.2020106797. Epub 2021 Mar 1.
Partitioning of the genome in meiosis occurs through two highly specialized cell divisions, named meiosis I and meiosis II. Step-wise cohesin removal is required for chromosome segregation in meiosis I, and sister chromatid segregation in meiosis II. In meiosis I, mono-oriented sister kinetochores appear as fused together when examined by high-resolution confocal microscopy, whereas they are clearly separated in meiosis II, when attachments are bipolar. It has been proposed that bipolar tension applied by the spindle is responsible for the physical separation of sister kinetochores, removal of cohesin protection, and chromatid separation in meiosis II. We show here that this is not the case, and initial separation of sister kinetochores occurs already in anaphase I independently of bipolar spindle forces applied on sister kinetochores, in mouse oocytes. This kinetochore individualization depends on separase cleavage activity. Crucially, without kinetochore individualization in meiosis I, bivalents when present in meiosis II oocytes separate into chromosomes and not sister chromatids. This shows that whether centromeric cohesin is removed or not is determined by the kinetochore structure prior to meiosis II.
在减数分裂过程中，基因组的分离通过两个高度特化的细胞分裂来实现，分别称为减数分裂 I 和减数分裂 II。在减数分裂 I 中，姐妹染色单体的分离需要逐步去除黏连蛋白，而在减数分裂 II 中，姐妹染色单体的分离则需要黏连蛋白的保护。在高分辨率共聚焦显微镜下观察到，单定向的姐妹动粒在减数分裂 I 中似乎融合在一起，而在减数分裂 II 中，当附着为双极时，它们则明显分开。有人提出，纺锤体施加的双极张力负责姐妹动粒的物理分离、黏连蛋白保护的去除以及减数分裂 II 中的染色单体分离。我们在这里表明，事实并非如此，姐妹动粒的初始分离早在减数分裂 I 的后期就已经发生，而与施加在姐妹动粒上的双极纺锤体力无关，在小鼠卵母细胞中就是如此。这种动粒个体化依赖于 separase 切割活性。至关重要的是，如果减数分裂 I 中没有动粒个体化，那么存在于减数分裂 II 卵母细胞中的二价体将分离成染色体而不是姐妹染色单体。这表明，在减数分裂 II 之前，姐妹着丝粒的黏连蛋白是否被去除取决于动粒的结构。
