Journal
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
Volume 117, Issue -, Pages 99-117Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcdb.2021.05.016
Keywords
Checkpoint; Kinetochores; Chromosome segregation; Mitosis; Aneuploidy; Catalysis
Categories
Funding
- Danish Cancer Society Scientific Committee (KBVU) [R146-A9322]
- Lundbeck Foundation [R215-2015-4081]
- Novo Nordisk Foundation [NNF19OC0058504]
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The spindle assembly checkpoint (SAC) is a surveillance mechanism that promotes accurate chromosome segregation in mitosis by sensing the attachment state of kinetochores. Current understanding of how SAC proteins are recruited to kinetochores in the absence of microtubule attachment and how attachments silence the SAC at the kinetochore is limited, requiring further investigation.
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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