Biomaterial Database

Principles and dynamics of spindle assembly checkpoint signalling. 2023

Andrew D McAinsh, and Geert J P L Kops

Centre for Mechanochemical Cell Biology, University of Warwick, Coventry, UK. a.d.mcainsh@warwick.ac.uk.

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.

UI	MeSH Term	Description	Entries
D008322	Mammals	Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.	Mammalia,Mammal
D008870	Microtubules	Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS.	Microtubule
D008941	Spindle Apparatus	A microtubule structure that forms during CELL DIVISION. It consists of two SPINDLE POLES, and sets of MICROTUBULES that may include the astral microtubules, the polar microtubules, and the kinetochore microtubules.	Mitotic Apparatus,Mitotic Spindle Apparatus,Spindle Apparatus, Mitotic,Meiotic Spindle,Meiotic Spindle Apparatus,Mitotic Spindle,Apparatus, Meiotic Spindle,Apparatus, Mitotic,Apparatus, Mitotic Spindle,Apparatus, Spindle,Meiotic Spindles,Mitotic Spindles,Spindle Apparatus, Meiotic,Spindle, Meiotic,Spindle, Mitotic,Spindles, Meiotic,Spindles, Mitotic
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D059566	M Phase Cell Cycle Checkpoints	The cellular signaling system that halts the progression of cells through MITOSIS or MEIOSIS if a defect that will affect CHROMOSOME SEGREGATION is detected.	M Phase Cell Cycle Checkpoint,M Phase Cell Cycle Arrest,M Phase Checkpoint,Mitotic Checkpoints,Mitotic Spindle Checkpoints,Spindle Assembly Checkpoint,Spindle Assembly Checkpoint Network,Assembly Checkpoint, Spindle,Assembly Checkpoints, Spindle,Checkpoint, M Phase,Checkpoint, Mitotic,Checkpoint, Mitotic Spindle,Checkpoint, Spindle Assembly,Checkpoints, M Phase,Checkpoints, Mitotic,Checkpoints, Mitotic Spindle,Checkpoints, Spindle Assembly,M Phase Checkpoints,Mitotic Checkpoint,Mitotic Spindle Checkpoint,Phase Checkpoint, M,Spindle Assembly Checkpoints,Spindle Checkpoint, Mitotic,Spindle Checkpoints, Mitotic
D018386	Kinetochores	Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.	Kinetochore
D018797	Cell Cycle Proteins	Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.	Cell Division Cycle Proteins,Cell-Cycle Regulatory Proteins,cdc Proteins,Cell Cycle Regulatory Proteins
D020090	Chromosome Segregation	The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.	Chromosome Segregations,Segregation, Chromosome,Segregations, Chromosome
D064173	Anaphase-Promoting Complex-Cyclosome	An E3 ubiquitin ligase primarily involved in regulation of the metaphase-to-anaphase transition during MITOSIS through ubiquitination of specific CELL CYCLE PROTEINS. Enzyme activity is tightly regulated through subunits and cofactors, which modulate activation, inhibition, and substrate specificity. The anaphase-promoting complex, or APC-C, is also involved in tissue differentiation in the PLACENTA, CRYSTALLINE LENS, and SKELETAL MUSCLE, and in regulation of postmitotic NEURONAL PLASTICITY and excitability.	Anaphase Promoting Complex