在有丝分裂过程中，通过均等的染色体分离，母代遗传信息精确地传递给子代细胞。染色体分离的失调会导致非整倍体和染色体不稳定性，促进癌症发生。因此，阐明有丝分裂过程中维持染色体稳定性的调控机制对于促进人类健康具有重要意义。CDK1激酶是促进有丝分裂进入的分子引擎，但是CDK1-Cyclin B1如何维系染色体在有丝分裂过程中的动态性和稳定性仍有待深入研究。我们拟结合我们的工作基础和预实验进展，揭示Cyclin B1动粒定位的分子基础，探究CDK1-Cyclin B1促进染色体排列的功能。我们也将解析CDK1如何调控Mps1的结构与功能来揭示纺锤体检验点的信息流。最后，我们拟阐明CDK1和PLK1协同磷酸化对Mis12复合物的生理功能的调控。我们希望通过本项目的实施，揭示CDK1调控有丝分裂染色体稳定性的分子机制,为阐明染色体不稳定性与肿瘤的发生发展提供理论基础。

During mitosis, through equal chromosome segregation, mother cell faithfully transmits the genetic information into two daughter cells. The failure of faithful chromosome segregation during mitosis will generate aneuploidy daughter cells and chromosomal instability (CIN). CIN will drive aggressive tumorigenesis by allowing tumor to evolve rapidly and acquire malignant transformation ability. Therefore, elaborating the faithful mitotic progression is of great value to promote the health of human being. CDK1 kinase is well-known as the engine of mitotic entry. However, the detailed function of CDK1-Cyclin B1 in maintaining chromosomal stability and and its mechanism were poorly understood so far. In this proposal, using hTERT-RPE1 cell as a model, we aim to uncover the molecular basis of kinetochore targeting of Cyclin B1 and explore the function of CDK1-Cyclin B1 in the maintenance of chromosomal stability. We also want to address how the CDK1 phosphorylation on Mps1 release its intro-molecualr interaction and the spindle checkpoint signaling. Last, we aim to elaborate the physiological significance of the concerted phosphorylation of CDK1 and Plk1 toward Mis12 complex. Overall, we aim to discover the molecular mechanism that how CDK1 ensure the chromosomal stability during mitosis. We hope our research will provide novel knowledge for the elucidation of chromosomal instability and tumorgenesis.