The BUB1 and BUBR1 paralogs scaffold the kinetochore corona

Abstract

The kinetochore corona, a polymeric fibrous structure, facilitates chromosome biorientation and mitotic checkpoint signaling during mitosis. How its main building block, the RZZ complex, assembles on the outer kinetochore remains poorly understood. Harnessing corona biochemical reconstitutions and cell biology, we reveal the paralogous checkpoint proteins BUB1 and BUBR1 promote non-redundant branches of corona assembly. MPS1-kinase-dependent kinetochore docking of BUB1 and subsequent recruitment of BUBR1 initiates assembly. Disrupting the first branch by depleting CENP-E, a kinesin that links BUBR1 to RZZ, uncovered a second assembly pathway mediated by a direct interaction between BUB1 and ROD. Discovery of a direct interaction with the RZZ explains how the SAC protein MAD1 fits this corona assembly scheme. Our findings solve the long-standing puzzle of corona assembly and demonstrate the intimate interweaving of chromosome biorientation and checkpoint signaling.