细胞的DNA损伤应激反应（DDR）是一个很复杂的过程，有多条信号通路和蛋白/分子参与这一过程，但其分子机制还远未明确。我们前期研究中发现染色体浓缩调控蛋白（RCC2）被DNA损伤诱导，且其表达改变对细胞DNA损伤程度有影响，提示RCC2极有可能参与了细胞的DDR。进一步研究发现RCC2与非同源末端连接（NHEJ）修复通路中的关键分子Ku结合，且RCC2与Ku的结合影响了NHEJ的效率。在前期工作基础上，本研究首先通过体内外实验验证RCC2-Ku之间的相互作用；进一步构建RCC2与Ku的突变体，鉴定二者相互作用的结构基础；并深入探讨RCC2-Ku互作对细胞DNA损伤、修复及细胞命运的影响，确定其在DDR中的作用；最后尝试发现RCC2-Ku互作在肿瘤发生中的作用。通过本研究将阐明RCC2参与DDR的可能分子机制，使我们对DDR有更进一步的理解，为肿瘤的预防甚至治疗提供有益信息。

DNA damage response (DDR) is a very complex process, and many molecules/signaling pathways are involved. However, the underlying molecular mechanism is far from clear. Previously, we have found that the regulator of chromosome condensation 2 (RCC2) was increased during DNA damage, and the changed expression influenced the degree of DNA damage, implying that RCC2 might be involved in DDR. Furthermore, it was shown that RCC2 can interact with Ku, a key molecule in non-homologous end-joining (NHEJ) repair, and the binding of RCC2 to Ku influenced NHEJ efficiency. In the present study, in vitro and in vivo experiments would be conducted to verified the RCC2-Ku interaction. Then the interacting domains on both proteins will be determined using a series of mutant proteins of RCC2 and Ku.. Based on the above finding, the effects of RCC2-Ku interaction DNA damage, DNA repair, and cell fate will be evaluated. And finally, the possible role of RCC2-Ku interaction in tumorigenesis will be assessed. Results obtained from these studies will provide a clear definition of RCC2 in DDR, which will help better understand the molecular mechanism for DDR as well as tumor prevention and treatment.