Spindelcheckpoint

Spindelcheckpoint, often called the spindle assembly checkpoint (SAC), is a conserved cell-cycle control mechanism that monitors chromosome alignment and attachment to the mitotic spindle. Its primary role is to ensure that sister chromatids are properly attached to opposite spindle poles and under adequate tension before the cell proceeds from metaphase to anaphase.

The checkpoint relies on a network of conserved proteins, including MAD1, MAD2, BUBR1/MAD3, BUB1, and BUB3, as well as kinases such as MPS1. When attachments are incorrect or tension is insufficient, these factors generate a wait signal that inhibits the activity of the anaphase-promoting complex/cyclosome (APC/C) by preventing activation of its co-activator Cdc20. As a result, substrates like securin and cyclin B are stabilized, delaying separase activation and progression into anaphase.

Functionally, the spindle checkpoint prevents chromosome mis-segregation and aneuploidy, contributing to genome stability during cell division. The signal is silenced once all kinetochores are properly attached and under tension, allowing APC/C-Cdc20 to trigger anaphase onset and subsequent mitotic exit.

Clinically and in research contexts, defects in spindle checkpoint signaling are associated with chromosomal instability seen in cancer. Conversely, some chemotherapeutic agents that disrupt microtubules activate the spindle checkpoint, contributing to mitotic arrest. The term is often used interchangeably with the spindle assembly checkpoint in studies of eukaryotic cell biology.