真核细胞分裂中染色体的正确分离与均匀分配依赖于动粒复合体。动粒功能缺陷会导致非整倍体等染色体异常，常造成肿瘤或遗传类疾病。动粒复合体分为内层CCAN和外层KMN，分别结合染色体着丝粒和纺锤体微管，在维持染色体稳定性与正确分离中发挥重要作用。CCAN内部的相互作用与分子组装是动粒形成并发挥功能的重要基础，是细胞分裂领域的研究前沿之一。我们曾报道CCAN核心亚基CENP-H/I/K复合物的结构与功能，揭示了CENP-H/I/K的分子组装模式及其在染色体分离中的动态特征，但是CCAN内部相互作用与动态组装机制并不清楚。本项目将在CENP-H/I/K复合物的结构与功能研究基础上，筛选并鉴定CENP-H/I/K介导的CCAN内部相互作用与分子组装模式，揭示蛋白激酶或微管张力对CENP-H/I/K动态组装的调控或响应机制，深入研究CENP-H/I/K复合物在染色体分离中的生物学功能。

In cell division of eukaryotes cell, the faithful segregation of chromosomes depends on the kinetochore complex. Dysfunction in kinetochore contributes to chromosome abnormalities such as aneuploidy, which cause tumors and genetic diseases. The kinetochore is divided into inner CCAN and outer KMN, which connect to centromere and spindle microtubule respectively， and play an important role in maintaining chromosome stability and faithful segregation. The interaction network and molecular assembly in CCAN are crucial bases for the formation and function of kinetochore, and one of the research frontiers in the field of cell division. We have reported the crystal structure of core subunit CENP-H/I/K complex of inner kinetochore CCAN previously, and revealed the molecular assembly model of CENP-H/I/K and its dynamic characteristics in chromosome segregation. However, the dynamic assembly mechanisms of CCAN are not clear. In this project，based on the structure and function study of CENP-H/I/K complex, we will screen and identify the interaction network and molecular assembly model of CCAN mediated by CENP-H/I/K, test and reveal the regulation or response mechanism of protein kinase or microtubule tension for dynamic assembly of CENP-H/I/K. The biochemical reconstitution and structural analysis, together with functional studies of CENP-H/I/K complex in chromosome segregation, are critical for the organizational principles of kinetochore.