Mammalian Oocyte Meiosis (MOM) UMR7622, Institut de Biologie Paris Seine, Sorbonne Université, 75005 Paris, France.
CNRS UMR7622 Developmental Biology Lab, Sorbonne Université, 75005 Paris, France.
Cells. 2020 Feb 7;9(2):390. doi: 10.3390/cells9020390.
Meiosis is required to reduce to haploid the diploid genome content of a cell, generating gametes-oocytes and sperm-with the correct number of chromosomes. To achieve this goal, two specialized cell divisions without intermediate S-phase are executed in a time-controlled manner. In mammalian female meiosis, these divisions are error-prone. Human oocytes have an exceptionally high error rate that further increases with age, with significant consequences for human fertility. To understand why errors in chromosome segregation occur at such high rates in oocytes, it is essential to understand the molecular players at work controlling these divisions. In this review, we look at the interplay of kinase and phosphatase activities at the transition from metaphase-to-anaphase for correct segregation of chromosomes. We focus on the activity of PP2A-B56, a key phosphatase for anaphase onset in both mitosis and meiosis. We start by introducing multiple roles PP2A-B56 occupies for progression through mitosis, before laying out whether or not the same principles may apply to the first meiotic division in oocytes, and describing the known meiosis-specific roles of PP2A-B56 and discrepancies with mitotic cell cycle regulation.
减数分裂是将细胞内的二倍体基因组内容减少到单倍体,从而产生具有正确染色体数目的配子——卵子和精子。为了实现这一目标,需要以时间控制的方式执行两次没有中间 S 期的专门细胞分裂。在哺乳动物雌性减数分裂中,这些分裂容易出错。人类卵子的错误率异常高,而且随着年龄的增长而增加,这对人类生育能力有重大影响。为了理解为什么在卵子中染色体分离会以如此高的速度出错,了解控制这些分裂的分子参与者是至关重要的。在这篇综述中,我们研究了在从中期到后期的转变过程中,激酶和磷酸酶活性的相互作用,以确保染色体的正确分离。我们重点关注 PP2A-B56 的活性,它是有丝分裂和减数分裂中启动后期的关键磷酸酶。我们首先介绍了 PP2A-B56 在有丝分裂过程中的多个作用,然后探讨了相同的原则是否可能适用于卵子的第一次减数分裂,并描述了 PP2A-B56 的已知减数分裂特异性作用以及与有丝分裂细胞周期调控的差异。