spindlecheckpoint

Spindle checkpoint, often referred to as the spindle assembly checkpoint (SAC), is a cellular safety mechanism that ensures accurate chromosome segregation during mitosis. It delays the onset of anaphase until all kinetochores are properly attached to spindle microtubules and under appropriate tension.

The checkpoint involves a conserved set of proteins, including MAD1, MAD2, BUB1, BUB3, BUBR1/Mad3, and Mps1, which become activated at unattached kinetochores and assemble the mitotic checkpoint complex (MCC) with CDC20. This MCC inhibits the anaphase-promoting complex/cyclosome (APC/C) and prevents degradation of securin and cyclin B, blocking separase activation and sister chromatid separation.

When all chromosomes are bi-oriented and under tension, the checkpoint is silenced. The MCC dissociates, APC/C-Cdc20 becomes active, securin and cyclin B are degraded, separase is activated, and the cell progresses from metaphase to anaphase and mitotic exit.

The spindle checkpoint is highly conserved across eukaryotes but varies in its components among organisms. Defects in SAC function can lead to aneuploidy and are characteristic of many cancers; some cancers exhibit SAC deficiencies that contribute to chromosomal instability and may influence responses to antimitotic therapies. Pharmacological inhibitors targeting SAC kinases, such as Mps1, are under investigation as potential cancer therapies.

In common usage, spindle assembly checkpoint refers to the same mechanism; spindle checkpoint is a shorthand sometimes used interchangeably.