Principles and dynamics of spindle assembly checkpoint signalling

TY - JOUR

T1 - Principles and dynamics of spindle assembly checkpoint signalling

AU - McAinsh, Andrew D

AU - Kops, Geert J P L

N1 - © 2023. Springer Nature Limited.

PY - 2023/8

Y1 - 2023/8

N2 - 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.

AB - 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.

KW - Animals

KW - M Phase Cell Cycle Checkpoints

KW - Spindle Apparatus/metabolism

KW - Kinetochores/metabolism

KW - Anaphase-Promoting Complex-Cyclosome/genetics

KW - Microtubules/metabolism

KW - Chromosome Segregation

KW - Cell Cycle Proteins/genetics

KW - Mammals/genetics

U2 - 10.1038/s41580-023-00593-z

DO - 10.1038/s41580-023-00593-z

M3 - Article

C2 - 36964313

SN - 1471-0072

VL - 24

SP - 543

EP - 559

JO - Nature reviews. Molecular cell biology

JF - Nature reviews. Molecular cell biology

IS - 8

ER -