Figure 10. Model for the role of dimerization in CPC interactions with the centromere.

Dimeric CPC stably binds at inner centromeres possibly via two Survivin-pH3^T3 interactions mediated by Borealin dimerization. Removing the dimerization domain of Borealin results in rapid exchange at inner centromeres since monomeric CPC might only contact a single pH3^T3 molecule. When endogenous Borealin is knocked-down, Borealin mutants lacking dimerization transiently associate with the centromere to provide partial function. However, when endogenous Borealin is present, dimerization-defective mutants compete for other CPC family members to increase their exchange and act as dominant negatives. At the kinetochore, dimeric CPC binds with a high rate of turnover potentially via dual pH2A^T120-Sgo1/2 interactions. These kinetochore-interactions are too weak to allow association in the context of a monomeric CPC. According to the prevailing model of CPC targeting, CPC interacts simultaneously with pH3^T3 via Survivin and pH2A^T120 via Sgo1/2. Our results do not preclude simultaneous binding, but do suggest that pH3^T3 would contribute most of the binding energy if this binding mode occurs. Theoretically, CPC monomers or dimers could simultaneously interact with single pH3^T3 and pH2A^T120.