Structural basis and dynamic regulation of kinetochore assembly

• Faithful chromosome segregation during mitosis requires the correct assembly of kinetochore on centromere. CENP-A is a variant of histone H3, which specializes the centromere region on chromatin and mediates the kinetochore assembly. The centromere loading of the newly-synthesized CENP-A is mediated by the Mis18 complex. The inner kinetochore protein CENP-N and CENP-C specifically recognize CENP-A-containing chromatin and recruit other proteins to form the inner kinetochore CCAN network (CENP-LN, CENP-C, CENP-HIKM, CENP-TWSX, CENP-OPQUR) at centromere. The CCAN network links to the microtubule-binding KMN network (the KNL1 complex, Mis12 complex and Ndc80 complex) to enable accurate chromosome segregation during cell division. One direction of our lab is to explore the structural basis and dynamic regulation of kinetochore assembly, including 1) the loading of CENP-A by Mis18 complex, 2) the recognition of CENP-A-containing chromatin by CCAN network, 3) the assembly of CCAN and KMN network, and 4) the attachment of kinetochore to microtubule.