The spindle assembly checkpoint (SAC) is a surveillance mechanism that promotes accurate chromosome segregation in mitosis. The checkpoint senses the attachment state of kinetochores, the proteinaceous structures that assemble onto chromosomes in mitosis in order to mediate their interaction with spindle microtubules. When unattached, kinetochores generate a diffusible inhibitor that blocks the activity of the anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase required for sister chromatid separation and exit from mitosis. Work from the past decade has greatly illuminated our understanding of the mechanisms by which the diffusible inhibitor is assembled and how it inhibits the APC/C. However, less is understood about how SAC proteins are recruited to kinetochores in the absence of microtubule attachment, how the kinetochore catalyzes formation of the diffusible inhibitor, and how attachments silence the SAC at the kinetochore. Here, we summarize current understanding of the mechanisms that activate and silence the SAC at kinetochores and highlight open questions for future investigation.

纺锤体装配检查点 (SAC) 是一种监测机制，可促进有丝分裂中准确的染色体分离。检查点检测动粒的附着状态，动粒是在有丝分裂中组装到染色体上的蛋白质结构，以介导它们与纺锤体微管的相互作用。未连接时，动粒会产生一种可扩散的抑制剂，阻断后期促进复合物/环体 (APC/C) 的活性，这是姐妹染色单体分离和退出有丝分裂所需的 E3 泛素连接酶。过去十年的工作极大地阐明了我们对可扩散抑制剂的组装机制以及它如何抑制 APC/C 的理解。然而，对于在没有微管附着的情况下，SAC 蛋白如何被募集到动粒上的了解较少，动粒如何催化可扩散抑制剂的形成，以及附件如何使动粒处的 SAC 沉默。在这里，我们总结了目前对在动粒处激活和沉默 SAC 的机制的理解，并强调了未来研究的未解决问题。