Stable MCC binding to the APC /C is required for a functional spindle assembly checkpoint

The spindle assembly checkpoint ( SAC ) delays progression into anaphase until all chromosomes have aligned on the metaphase plate by inhibiting Cdc20, the mitotic co‐activator of the APC /C. Mad2 and BubR1 bind and inhibit Cdc20, thereby forming the mitotic checkpoint complex ( MCC ), which can bind stably to the APC /C. Whether MCC formation per se is sufficient for a functional SAC or MCC association with the APC /C is required remains unclear. Here, we analyze the role of two conserved motifs in Cdc20, IR and C‐Box, in binding of the MCC to the APC /C. Mutants in both motifs assemble the MCC normally, but IR motif integrity is particularly important for stable binding to the APC /C. Cells expressing Cdc20 with a mutated IR motif have a compromised SAC , as uninhibited Cdc20 can compete with the MCC for APC /C binding and activate it. We thus show that stable MCC association with the APC /C is critical for a functional SAC .