Spindle assembly checkpoint activation and silencing at kinetochores.

Spindle assembly checkpoint activation and silencing at kinetochores.
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DOI:
10.1016/j.semcdb.2021.06.009
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发表时间:
2021-09
影响因子:
7.3
通讯作者:
Desai A
Desai A
中科院分区:
生物学2区
文献类型:
--
作者:
Lara-Gonzalez P;Pines J;Desai A

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纺锤体组装检查点(SAC)是一种监测机制,它促进有丝分裂中染色体的准确分离。检查点感知动点的附着状态,动点是在有丝分裂中聚集在染色体上的蛋白质结构,以调节它们与纺锤体微管的相互作用。当动粒独立时,会产生一种可扩散的抑制物,阻止后期促进复合体/环体(APC/C)的活性,APC/C是姐妹染色单体分离和退出有丝分裂所必需的E3泛素连接酶。过去十年的工作极大地启发了我们对可扩散抑制物组装机制的理解,以及它是如何抑制APC/C的。然而,对于在没有微管附着的情况下SAC蛋白如何被招募到动点,动粒如何催化扩散抑制物的形成,以及附着如何使动粒上的SAC沉默,我们了解得很少。在这里,我们总结了目前对激活和沉默SAC的机制的理解,并强调了未来研究的开放问题。
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.
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