Principles and dynamics of spindle assembly checkpoint signalling

Andrew D McAinsh, Geert J P L Kops

Research output: Contribution to journal/periodicalArticleScientificpeer-review

39 Citations (Scopus)

Abstract

The transmission of a complete set of chromosomes to daughter cells during cell division is vital for development and tissue homeostasis. The spindle assembly checkpoint (SAC) ensures correct segregation by informing the cell cycle machinery of potential errors in the interactions of chromosomes with spindle microtubules prior to anaphase. To do so, the SAC monitors microtubule engagement by specialized structures known as kinetochores and integrates local mechanical and chemical cues such that it can signal in a sensitive, responsive and robust manner. In this Review, we discuss how SAC proteins interact to allow production of the mitotic checkpoint complex (MCC) that halts anaphase progression by inhibiting the anaphase-promoting complex/cyclosome (APC/C). We highlight recent advances aimed at understanding the dynamic signalling properties of the SAC and how it interprets various naturally occurring intermediate attachment states. Further, we discuss SAC signalling in the context of the mammalian multisite kinetochore and address the impact of the fibrous corona. We also identify current challenges in understanding how the SAC ensures high-fidelity chromosome segregation.

Original languageEnglish
Pages (from-to)543-559
Number of pages17
JournalNature reviews. Molecular cell biology
Volume24
Issue number8
DOIs
Publication statusPublished - Aug 2023

Keywords

  • Animals
  • M Phase Cell Cycle Checkpoints
  • Spindle Apparatus/metabolism
  • Kinetochores/metabolism
  • Anaphase-Promoting Complex-Cyclosome/genetics
  • Microtubules/metabolism
  • Chromosome Segregation
  • Cell Cycle Proteins/genetics
  • Mammals/genetics

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