Spindle Assembly Checkpoint (SAC) (SAC)

The Spindle Assembly Checkpoint (SAC) is a highly conserved cell cycle surveillance mechanism that ensures the fidelity of chromosome segregation by delaying the transition from metaphase to anaphase until all kinetochores are properly attached to spindle microtubules (Musacchio, 2011, Science). In the context of paclitaxel treatment, the drug stabilizes microtubules, thereby preventing the generation of mechanical tension across sister kinetochores, which is a key signal for SAC satisfaction (Weaver, 2014, Mol. Biol. Cell). This results in a chronic activation of the SAC, where the Mitotic Checkpoint Complex (MCC)—comprising MAD2, BUBR1, and BUB3—sequesters CDC20, thereby inhibiting the Anaphase-Promoting Complex/Cyclosome (APC/C) (Sivakumar & Gorbsky, 2015, Curr. Biol.). The resulting prolonged mitotic arrest, often termed mitotic arrest, eventually leads to cell death via apoptosis or a slow exit into a senescent G1 state known as mitotic slippage (Topham & Taylor, 2013, Curr. Opin. Cell Biol.). While paclitaxel is the most well-known inducer of this state, the SAC itself is a focus of drug development, with inhibitors of SAC kinases like MPS1 (TTK) being evaluated to override the checkpoint and force lethal premature mitotic exit in cancer cells.

Other names

Mitotic checkpointM-phase checkpointSpindle checkpointMitotic Spindle Assembly Checkpoint

Microtubule stabilization leading to chronic Spindle Assembly Checkpoint activation, APC/C inhibition, and mitotic arrest followed by apoptosis.