145289.fig.001a
(a)
145289.fig.001b
(b)
Figure 1: Current models of the signaling pathway of the spindle assembly checkpoint (SAC). (a) According to the first model, the presence of unattached or inappropriate attached kinetochores activates the SAC (SAC on). At the kinetochore level, the complex Mad1-“closed” Mad2 generates a diffusible signal, converting the cytosolic “Open” Mad2 into new “Closed” Mad2, which in association with Bub3, BubR1, and Cdc20 forms the mitotic checkpoint complex. Mitotic checkpoint complex (MCC) sequesters Cdc20 preventing activation of the anaphase promoting complex/cyclosome (APC/C). Once all chromosomes are properly attached, MCC disassembles (SAC off) and Cdc20 is free to activate the APC/C that targets Securin and Cyclin B for degradation. This way, Separase is released and cleaves Coesins allowing sister chromatid separation, while Cyclin B degradation allows mitosis exit. (b) According to the second model, cytosolic “closed” Mad2 promotes a conformational change in Cdc20, allowing its binding to the N terminus of BubR1 bound to Bub3, which maintain the APC/C inhibited thus preventing anaphase onset. Once this complex is formed, “closed” Mad2 is released and returns to cytosol.