The internal ​Cdc20 binding site in ​BubR1 facilitates both spindle assembly checkpoint signalling and silencing

Tiziana Lischetti, Gang Zhang, Garry G. Sedgwick, Victor M. Bolanos-Garcia & Jakob Nilsson

Improperly attached kinetochores activate the spindle assembly checkpoint (SAC) and by an unknown mechanism catalyse the binding of two checkpoint proteins, ​Mad2 and ​BubR1, to ​Cdc20 forming the mitotic checkpoint complex (MCC). Here, to address the functional role of ​Cdc20 kinetochore localization in the SAC, we delineate the molecular details of its interaction with kinetochores. We find that ​BubR1 recruits the bulk of ​Cdc20 to kinetochores through its internal Cdc20 binding domain (IC20BD). We show that preventing ​Cdc20 kinetochore localization by removal of the IC20BD has a limited effect on the SAC because the IC20BD is also required for efficient SAC silencing. Indeed, the IC20BD can disrupt the MCC providing a mechanism for its role in SAC silencing. We thus uncover an unexpected dual function of the second ​Cdc20 binding site in ​BubR1 in promoting both efficient SAC signalling and SAC silencing.