有丝分裂灾变死亡是电离辐射诱发细胞死亡的主要形式之一，目前其发生的分子机制尚不明确。我们的前期工作表明p53诱导基因3(p53-inducible gene 3, PIG3)定位于有丝分裂期纺锤体结构，缺失PIG3细胞微管生长速度显著变慢，出现有丝分裂期染色体错误排列等有丝分裂异常现象。此外，PIG3受辐射诱导表达并存在良好的剂量-效应关系，且与DNA双链断裂损伤修复因子DNA-PKcs存在直接相互作用。而DNA-PKcs抑制电离辐射诱发的有丝分裂灾变。基于上述证据，我们提出研究设想，DNA-PKcs-PIG3-ROS偶联调控电离辐射诱发的DNA损伤修复和有丝分裂进程。本课题将重点探讨，1）DNA-PKcs与PIG3相互调控关系；2）DNA-PKcs-PIG3-ROS信号通路对电离辐射诱发的有丝分裂灾变中的调节作用；3）DNA-PKcs-PIG3-ROS信号通路在辐射防护中的应用潜能研究。

Mitotic catastrophe is one of the main forms of cell death induced by ionizing radiation. However, the molecular mechanism has not been fully elucidated. Our preliminary data showed that p53-inducible gene 3 (PIG3) localizes at the mitotic spindle structure. Depletion of PIG3 inhibits microtubule growth, and causes mitotic aberrant including chromosome misalignment at metaphase. Moreover, the expression of PIG3 is induced by irradiation in a dose dependent manner and PIG3 could directly interact with DNA-PKcs which is an essential regulator of DNA DSBs NHEJ repair and is also reported to inhibit mitotic catastrophe. Based on the above evidence, we hypothesize that DNA-PKcs-PIG3 -ROS signal pathway might be an important regulator coupled irradiation induced DNA damage response and mitosis progression. In this project, we will further determine: 1) the relationship between DNA-PKcs and PIG3; 2) the regulation role of DNA-PKcs-PIG3-ROS signal pathway on radiation induced mitotic catastrophe; 3) the potential application of DNA-PKcs-PIG3-ROS signal pathway in radiation protection.