Centre for Mechanochemical Cell Biology & Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Gibbet Hill, Coventry, CV4 7AL, UK.
Centre for Mechanochemical Cell Biology & Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Gibbet Hill, Coventry, CV4 7AL, UK.
Curr Biol. 2018 Sep 10;28(17):R929-R930. doi: 10.1016/j.cub.2018.07.040.
Error-free chromosome segregation during mitosis depends on a functional spindle assembly checkpoint (SAC). The SAC is a multi-component signalling system that is recruited to unattached or incorrectly attached kinetochores to catalyse the formation of a soluble inhibitor, known as the Mitotic Checkpoint Complex (MCC), which binds and inhibits the anaphase promoting complex (APC/C) [1]. We have previously proposed that two separable pathways, composed of KNL1-Bub3-Bub1 (KBB) and Rod-Zwilch-Zw10 (RZZ), recruit Mad1-Mad2 complexes to human kinetochores to activate the SAC [2]. Although Bub1 is absolutely required for checkpoint signalling in yeast (which lack RZZ), there is conflicting evidence as to whether this is the case in human cells based on siRNA studies [2-5]. Here we show that, while Bub1 is required for recruitment of BubR1, it is not strictly required for the checkpoint response to unattached kinetochores in diploid human cells.
在有丝分裂过程中，染色体的无差错分离依赖于功能正常的纺锤体组装检查点（SAC）。SAC 是一种多组分信号系统，当未连接或连接不正确的动粒时，它会被募集到动粒上，以催化可溶性抑制剂的形成，这种抑制剂被称为有丝分裂检查点复合物（MCC），它可以结合并抑制后期促进复合物（APC/C）[1]。我们之前提出，由 KNL1-Bub3-Bub1（KBB）和 Rod-Zwilch-Zw10（RZZ）组成的两个可分离的途径将 Mad1-Mad2 复合物募集到人类动粒上，以激活 SAC[2]。尽管 Bub1 在酵母中（缺乏 RZZ）的检查点信号传导中是绝对必需的，但基于 siRNA 研究，关于在人类细胞中是否也是如此存在矛盾的证据[2-5]。在这里，我们表明，虽然 Bub1 对于 BubR1 的募集是必需的，但在二倍体人类细胞中，它对于未连接的动粒的检查点反应并不是严格必需的。
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