细胞中DNA双链断裂（DSB）通常由经典非同源末端连接修复（C-NHEJ）和同源重组修复完成。抗体类别转换（CSR）仅依赖于C-NHEJ通路。我们发现在LigaseIV敲除的C-NHEJ缺陷的小鼠B细胞中，CSR仍然发生，显示有新的DSB修复途径存在，这个修复途径被命名为选择性末端连接修复（A-EJ），但作用于A-EJ的修复因子未知。我们在LigaseIV-/-细胞中共敲除LigaseIII的辅助因子XRCC1，发现LigaseIII/XRCC1复合体不作用于A-EJ通路（PNAS；2012；IF：9.8）。在本课题中，我们将继续研究参与A-EJ的修复因子和A-EJ在细胞中的生理意义，包括LigaseI是否参与A-EJ并修复DSB，A-EJ在维持基因组稳定性的作用。以上研究可以扩展我们对DNA修复机制的理解，并为DNA修复缺陷所导致疾病（如恶性肿瘤）的发生提供理论基础。

In cells, DNA double strand breaks are repaired by classic non-homologous end joining (C-NHEJ) and the homologous recombination repair(HRR). Class switch recombination (CSR) is relied on the C-NHEJ pathway based on DNA LigaseIV. We found, in LigaseIV-/- mouse B cells, CSR still occurs although the efficiency of CSR was decreased, which suggested the existence of a noval DNA repair pathway. This new DSB repair pathway was named as alternative end joining (A-EJ) pathway. The repair factors in A-EJ were not defined. We knocked out the co-factor of LigaseIII, XRCC1, and found LigaseIII/XRCC1 complex do not play roles in A-EJ pathway (PNAS;2012;IF:9.8). In this proposal, we will continue to study the repair factors in A-EJ and the physiological functions of A-EJ pathway in cells. We will study the role of LigaseI in A-EJ and the function of A-EJ in maintaining genomic stabiligy of cells . These studies will expand our understanding of DNA repair, and also provide us the theoretic evidences of diseases(such as the malignant tumors) caused by DNA repair deficiency and genomic instability.