Fig. 1

Integrated model of spindle assembly and spindle position checkpoints in mitosis. (A) The Spindle Position Checkpoint (SPOC) monitors spindle alignment through the Bfa1Bub2 complex. Misaligned spindle pole bodies (SpbM) transition to aligned state (SpbA). When spindle misalignment is detected, Kin4 inhibits Cdc5, maintaining the Bfa1Bub2-Tem1 complex in an active state that prevents mitotic exit. Proper spindle orientation creates alignment-dependent silencing through SpbA-mediated Bfa1Bub2Tem1 dissociation, leading to Tem1 release and MEN activation. (B) Checkpoint Signals originating from SPB and unattached kinetochores (Kin U) coordinate both pathways, with Cdc5 serving as a central mediator of checkpoint crosstalk. Cdc5 provides dual checkpoint silencing by simultaneously promoting dissociation of both APC/C:MCC and Bfa1Bub2Tem1 complexes. (C) The Spindle Assembly Checkpoint (SAC) monitors kinetochore-microtubule attachments. Unattached kinetochores (KinU) transition to attached state (KinA). In the absence of amphitelic attachment, Mad2 forms complexes with Cdc20, Bub3, and Mad3, inhibiting APC/C activation. Upon proper chromosome attachment, KinA creates tension-dependent positive feedback that promotes APC/C:MCC dissociation, generating the ultrasensitive switch-like behavior essential for bistability. APC/C activation promotes the degradation of Pds1 (securin) and Clb2 (Cyclin B), which leads to sister chromatid separation and mitotic exit, respectively. The integration of these feedback mechanisms-tension-dependent positive feedback, alignment-dependent silencing, and Cdc5-mediated coordination-ensures robust checkpoint control and that cells only exit mitosis when both spindle positioning and chromosome attachment are correctly established.