UPMC Université Paris 06, UMR7622 Laboratoire de Biologie du Développement, 9 quai St. Bernard, Paris 75005, France.
Cell Rep. 2012 Nov 29;2(5):1077-87. doi: 10.1016/j.celrep.2012.10.002. Epub 2012 Nov 1.
In meiosis, two specialized cell divisions allow the separation of paired chromosomes first, then of sister chromatids. Separase removes the cohesin complex holding sister chromatids together in a stepwise manner from chromosome arms in meiosis I, then from the centromere region in meiosis II. Using mouse oocytes, our study reveals that cyclin A2 promotes entry into meiosis, as well as an additional unexpected role; namely, its requirement for separase-dependent sister chromatid separation in meiosis II. Untimely cyclin A2-associated kinase activity in meiosis I leads to precocious sister separation, whereas inhibition of cyclin A2 in meiosis II prevents it. Accordingly, endogenous cyclin A is localized to kinetochores throughout meiosis II, but not in anaphase I. Additionally, we found that cyclin B1, but not cyclin A2, inhibits separase in meiosis I. These findings indicate that separase-dependent cohesin removal is differentially regulated by cyclin B1 and A2 in mammalian meiosis.
在减数分裂中，两次特殊的细胞分裂首先允许同源染色体分离，然后是姐妹染色单体分离。分离酶以逐步的方式从减数分裂 I 的染色体臂上，然后从减数分裂 II 的着丝粒区域去除将姐妹染色单体结合在一起的黏连蛋白复合物。我们的研究使用小鼠卵母细胞揭示了周期蛋白 A2 促进进入减数分裂，以及一个额外的意外作用；即，它对减数分裂 II 中依赖分离酶的姐妹染色单体分离的要求。减数分裂 I 中过早的周期蛋白 A2 相关激酶活性导致姐妹染色单体过早分离，而抑制减数分裂 II 中的周期蛋白 A2 则阻止其发生。因此，内源性周期蛋白 A 在整个减数分裂 II 中定位于动粒，但不在有丝分裂 I 中。此外，我们发现周期蛋白 B1 但不是周期蛋白 A2 在减数分裂 I 中抑制分离酶。这些发现表明，在哺乳动物减数分裂中，黏连蛋白的分离酶依赖性去除由周期蛋白 B1 和 A2 差异调节。
