Figure 3.

SAC silencing with asymmetric spindle pole clustering and merotelic kinetochore attachments. (KT) Kinetochore; (SP) spindle pole. (A) Spatiotemporal pattern of cyclin B during spindle pole clustering. (i and ii) Steady-state cyclin B pattern before and after the last kinetochore attachment. Cyclin B degradation is not triggered, and the patterns persist. (iii) Cyclin B pattern with two clustered spindle poles right before SAC silencing is triggered. (iv–vi) Propagation of cyclin B degradation with two clustered spindle poles. (B) Probability of SAC silencing and anaphase onset in a multipolar spindle in the presence of signal noise at the spindle pole. Results from 100 stochastic simulations. Error bars show mean ± SE estimated via the Wald method. (C) Phase diagram of mitotic fate given degrees of spindle pole clustering and dissociation rates of SAC components from the spindle pole (k_offSP; see Table S1). (D) Illustration of the effect of merotelic attachment on kinetochore tension. Normal tension with amphitelic attachment pulls the outer kinetochore away from the inner centromere, where kinase activity is centered. Merotelic attachment could pull part of the outer kinetochore back toward the inner centromere region and effectively increase the kinase activity on the outer kinetochore. Kinase activity at a merotelic attachment may thus resemble that at an attached kinetochore with weakly reduced tension. (E) Effects of reduction in kinetochore tension at one merotelically attached kinetochore on the spindle pole signal in a normal bipolar spindle. Reduction in kinetochore tension promotes recruitment of SAC components onto the kinetochore and/or inhibits transport activation from the kinetochore. Exactly how the rates depend on kinetochore tension is unknown. (Translucent blue arrows) Examples of the rate-tension dependence. For simplicity, by default the reduction of kinetochore tension first reduces the transport activation rate, and then increases the recruitment rate (bent blue arrow, see Fig. S2 for details). (F) Phase diagram of mitotic fate given degrees of spindle pole clustering and kinetochore tension at one merotelically attached kinetochore. (E and F) One kinetochore out of 10 is assigned the weakened tension. (B, C, and F) The anaphase onset refers to those cases in which cyclin B is degraded within 2 h after the last kinetochore attachment; otherwise the mitotic fate is assigned as arrest.