DNA-PKcs不仅在电离辐射诱导的DNA双链断裂损伤修复中有关键作用，还具有调节电离辐射损伤细胞的有丝分裂进程和中心体与纺锤体稳定的功能，SIK2是最近报导的另一调控中心体分离和双极纺锤体形成的分子。我们前期研究发现DNA-PKcs与SIK2有相互作用，二者是否协同调节电离辐射损伤细胞的有丝分裂进程反应及机制值得关注。本课题就DNA-PKcs与SIK2相互作用方式，及其相互作用在放射损伤细胞的纺锤体结构稳定和G2/M检查点功能的作用，其缺失是否引起放射损伤细胞有丝分裂灾变进行深入探讨。通过本课题的研究不仅可以阐明DNA-PKcs与SIK2参与有丝分裂灾变的分子机制，而且为传统化疗药物有耐药性的肿瘤的治疗开辟了新的途径，有望成为开发新抗癌药物的分子靶向目标。

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) plays a significant role in the process of non-homologous end-joining (NHEJ) repair, which is one of the major pathways for the IR-induced DSBs in mammalian cells. Cells that lack or have inactive DNA-PKcs have defects in repairing DSBs, disordered regulation of mitotic progress，which could even lead to mitotic catastrophe. Therefore, identifying the upstream and downstream regulators of DNA-PKcs and recognizing their functions have great significance in understand the repairing mechanism of IR-induced DNA damage. In our previous experiments, the salt-inducible kinase 2 (SIK2) was identified to have interaction with DNA-PKcs by the yeast two-hybridization assay. It was reported that SIK2 was located at centrosome, played a key role in the initiation of mitosis, could phosphorylate the centrosome linker protein, C-Nap1. Overexpression of SIK2 induced centrosome splitting and depletion of SIK2 delayed mitotic progression. Recently we also found DNA-PKcs played roles in regulating mitotic progression of IR-induced cell, stabilizing spindle and centrosome. In our previous study, the interaction of SIK2 and DNA-PKcs has been identified by GST-pulldown assay and Co-IP. In this study we plan to elucidate how DNA-PKcs interacts with SIK2 and whether their interaction would functions in centrosome separation，spindle stability and mitotic progression post irradiation. Moreover whether the disruption of their interaction would lead to mitotic catastrophe post irradiation will be determined. Together with all these, The roles of the interaction of SIK2 and DNA-PKcs in G2/M arrest, spindle structure, mitotic progress and mitotic catastrophe post irradiationwill be ascertained, which will extend our understanding in molecular mechanism of cell radiosensitivity，and also provide us theoretical basis of SIK2 as the potential molecalar target for therapy in cancer.