细胞的DNA损伤应激反应（DDR）是一个非常复杂的调控系统。我们和他人在对DDR的研究中发现DNA损伤可引起许多剪接因子的变化，最终导致变异剪接（AS）的发生。但是这众多的剪接因子究竟是发挥了同等作用，还是某些的作用更为关键，目前还没有任何定论。结合当前肿瘤研究的最新进展与我们前期研究结果，我们认为剪接子（spliceosome）中的一个核心复合物U2 snRNP极有可能在DNA损伤诱导的AS过程中发挥关键作用。本研究将围绕这一问题，首先探讨DNA损伤对U2 snRNP各主要成分的影响；进一步分析U2 snRNP在DDR中的作用；并通过比较正常与异常U2 snRNP状态下DNA损伤诱导的AS改变确定其在这一过程中的作用；最终在动物模型中对相关发现加以验证。以上研究将明确U2 snRNP在DDR以及DNA损伤诱导的AS中的作用，为更深入理解DDR分子机制，肿瘤的预防和治疗提供有益信息。

Cellular DNA damage response (DDR) is a very complex regulatory network. Previously, we and others have found that DNA damage can induce changes in many splicing factors (SF), and eventually lead to alternative splicing (AS). However, whether the functions of these SFs are equally important, or some are more important than the others, is still not clear. Based on the current progress in cancer research and our results, it is hypothesized that the key complex in spliceosome, U2 snRNP, might be important for DNA damage-induced AS. The present study will foucs on this hypothesis. First, the effects of DNA damage on key components of U2 snRNP will be examined. Then the function of U2 snRNP in DDR will be explored. By comparing the AS under normal or mutant U2 snRNP, the role of U2 snRNP during this process will be determined. Finally, such observation will be verified by using animal model. The above study will determine the function of U2 snRNP in DDR and DNA damage-induced AS, which will provide useful information for the better understanding of DDR, as well as the prevention and treatment of cancer.