Institut Jacques Monod, Université Paris Cité, CNRS, 75013 Paris, France.
Cells. 2022 Oct 27;11(21):3399. doi: 10.3390/cells11213399.
The key to gametogenesis is the proper execution of a specialized form of cell division named meiosis. Prior to the meiotic divisions, the recombination of maternal and paternal chromosomes creates new genetic combinations necessary for fitness and adaptation to an ever-changing environment. Two rounds of chromosome segregation -meiosis I and II- have to take place without intermediate S-phase and lead to the creation of haploid gametes harboring only half of the genetic material. Importantly, the segregation patterns of the two divisions are fundamentally different and require adaptation of the mitotic cell cycle machinery to the specificities of meiosis. Separase, the enzyme that cleaves Rec8, a subunit of the cohesin complex constituting the physical connection between sister chromatids, has to be activated twice: once in meiosis I and immediately afterwards, in meiosis II. Rec8 is cleaved on chromosome arms in meiosis I and in the centromere region in meiosis II. This step-wise cohesin removal is essential to generate gametes of the correct ploidy and thus, embryo viability. Hence, separase control and Rec8 cleavage must be perfectly controlled in time and space. Focusing on mammalian oocytes, this review lays out what we know and what we still ignore about this fascinating mechanism.
配子发生的关键是一种特殊形式的细胞分裂——减数分裂的正确执行。在减数分裂之前，母本和父本染色体的重组会产生新的遗传组合，这对于适应不断变化的环境是必要的。必须进行两轮染色体分离——减数分裂 I 和减数分裂 II——而没有中间的 S 期，导致形成只携带一半遗传物质的单倍体配子。重要的是，这两个分裂的分离模式从根本上是不同的，需要有丝分裂细胞周期机制适应减数分裂的特殊性。分离酶是一种酶，它可以切割 Rec8，Rec8 是构成姐妹染色单体之间物理连接的黏连蛋白复合物的一个亚基。分离酶必须被激活两次：一次在减数分裂 I 中，紧接着在减数分裂 II 中。Rec8 在减数分裂 I 中在染色体臂上被切割，在减数分裂 II 中在着丝粒区域被切割。这种逐步去除黏连蛋白对于产生正确倍性的配子，从而胚胎活力，是必不可少的。因此，分离酶的控制和 Rec8 的切割必须在时间和空间上得到精确控制。本文以哺乳动物卵母细胞为重点，阐述了我们对这一迷人机制的了解和仍不清楚的地方。
