Marston Adele L, Wassmann Katja
Wellcome Centre for Cell Biology, Institute for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
Sorbonne Universités, UPMC Univ Paris 06, Institut de Biologie Paris Seine, UMR7622, Paris, France.
Front Cell Dev Biol. 2017 Dec 13;5:109. doi: 10.3389/fcell.2017.00109. eCollection 2017.
Cell division in mitosis and meiosis is governed by evolutionary highly conserved protein kinases and phosphatases, controlling the timely execution of key events such as nuclear envelope breakdown, spindle assembly, chromosome attachment to the spindle and chromosome segregation, and cell cycle exit. In mitosis, the spindle assembly checkpoint (SAC) controls the proper attachment to and alignment of chromosomes on the spindle. The SAC detects errors and induces a cell cycle arrest in metaphase, preventing chromatid separation. Once all chromosomes are properly attached, the SAC-dependent arrest is relieved and chromatids separate evenly into daughter cells. The signaling cascade leading to checkpoint arrest depends on several protein kinases that are conserved from yeast to man. In meiosis, haploid cells containing new genetic combinations are generated from a diploid cell through two specialized cell divisions. Though apparently less robust, SAC control also exists in meiosis. Recently, it has emerged that SAC kinases have additional roles in executing accurate chromosome segregation during the meiotic divisions. Here, we summarize the main differences between mitotic and meiotic cell divisions, and explain why meiotic divisions pose special challenges for correct chromosome segregation. The less-known meiotic roles of the SAC kinases are described, with a focus on two model systems: yeast and mouse oocytes. The meiotic roles of the canonical checkpoint kinases Bub1, Mps1, the pseudokinase BubR1 (Mad3), and Aurora B and C (Ipl1) will be discussed. Insights into the molecular signaling pathways that bring about the special chromosome segregation pattern during meiosis will help us understand why human oocytes are so frequently aneuploid.
有丝分裂和减数分裂中的细胞分裂由进化上高度保守的蛋白激酶和磷酸酶控制，这些酶控制着关键事件的适时执行，如核膜破裂、纺锤体组装、染色体附着于纺锤体以及染色体分离，还有细胞周期退出。在有丝分裂中，纺锤体组装检查点（SAC）控制染色体在纺锤体上的正确附着和排列。SAC检测错误并诱导细胞周期在中期停滞，防止染色单体分离。一旦所有染色体都正确附着，依赖SAC的停滞就会解除，染色单体均匀地分离到子细胞中。导致检查点停滞的信号级联依赖于从酵母到人类都保守的几种蛋白激酶。在减数分裂中，通过两次特殊的细胞分裂，从二倍体细胞产生含有新基因组合的单倍体细胞。虽然明显不那么稳健，但SAC控制在减数分裂中也存在。最近发现，SAC激酶在减数分裂过程中执行精确的染色体分离方面还有其他作用。在这里，我们总结了有丝分裂和减数分裂细胞分裂之间的主要差异，并解释了为什么减数分裂对正确的染色体分离提出了特殊挑战。描述了SAC激酶鲜为人知的减数分裂作用，重点关注两个模型系统：酵母和小鼠卵母细胞。将讨论经典检查点激酶Bub1、Mps1、假激酶BubR1（Mad3）以及极光激酶B和C（Ipl1）的减数分裂作用。对减数分裂过程中导致特殊染色体分离模式的分子信号通路的深入了解将有助于我们理解为什么人类卵母细胞如此频繁地出现非整倍体。
