Figure 8.

The dual control mechanisms of the spindle checkpoint. (A) Activation of the spindle checkpoint early at prometaphase triggers Cdc20p degradation. The reduced level of Cdc20p ensures that the residual Cdc20p can be efficiently inhibited through binding with the spindle checkpoint proteins. Cdc20p remains inhibited even toward late prometaphase when only a few unattached kinetochores exist and the ability to assemble the Cdc20p–checkpoint protein complex has declined. After metaphase is achieved, both inhibitory mechanisms on Cdc20p are lifted. Cdc20p then accumulates and is able to activate APC. (B) Without degradation of Cdc20p in response to spindle checkpoint signal, the elevated level of Cdc20p overcomes the binding and inhibition by the spindle checkpoint proteins, especially toward late prometaphase. The inefficient inhibition of Cdc20p leads to premature anaphase before metaphase is achieved.