细胞核分布基因C样蛋白2在胞质分裂过程中的作用及机制研究

胞质分裂是指在细胞有丝分裂后期，细胞质一分为二分配到两个子细胞的过程。胞质分裂异常可导致基因组遗传不稳定，并与肿瘤等疾病发生发展密切相关。本课题组长期致力于细胞核分布基因C（NudC）家族生物学的功能研究。我们发现，NudC家族成员NudCL2（NudC-like protein 2）定位于胞质分裂的关键细胞器（中体）上，敲除NudCL2可导致中体结构受损及多核细胞比例增多等胞质分裂异常现象。蛋白定量质谱检测和免疫印迹实验结果显示，NudCL2敲除使得染色体浓缩调节因子RCC2蛋白水平显著下调。RCC2也定位于中体，其表达下调可产生与NudCL2敲除类似的胞质分裂异常表型。此外，我们还发现NudCL2在体外可发生蛋白相分离现象。本项目拟系统研究NudCL2及其相分离在胞质分裂中的作用及分子调控机制，为细胞分裂异常相关疾病（如肿瘤）的诊治提供新线索。

Cytokinesis is a key step in the later stage of cell cycle in eukaryotes that partitions cellular contents into daughter cells. It is a highly complex and precisely regulated process. Defects in cytokinesis lead to the failure of the early cell division process, and result in chromosomal instability that has been implicated in a wide range of human diseases, including cancer. We focus on the biological function of nuclear distribution gene C (NudC) family for many years. Recently, we find that NudCL2 (NudC-like protein 2) is localized at midbody, an important structural organelle formed during cytokinesis. Knockout of NudCL2 using the CRISPR/Cas9-based genome editing leads to the defects in cytokinesis, including the structural damage of midbody and the increased proportion of multinucleated cells. Our further results reveal that RCC2 (regulator of chromosome condensation 2) is downregulated in NudCL2 knockout cells. RCC2 is localized at the midbody. Its depletion leads to the similar defects with NudCL2 knockout. Thus, we propose that NudCL2 may play an important role in the cytokinesis regulation by stabilizing RCC2. In addition, our studies also show that NudCL2 undergoes phase separation in vitro. In this proposal, we will systematically characterize the role of NudCL2 in cytokinesis, and elucidate its possible molecular mechanism, which may provide a novel potential therapeutic target for the human diseases related to the defects of cytokinesis, including cancer.