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TY - JOUR AU - Xing, Mengtan AU - Yang, Mingrui AU - Huo, Wei AU - Feng, Feng AU - Wei, Leizhen AU - Jiang, Wenxia AU - Ning, Shaokai AU - Yan, Zhenxin AU - Li, Wen AU - Wang, Qingsong AU - Hou, Mei AU - Dong, Chunxia AU - Guo, Rong AU - Gao, Ge AU - Ji, Jianguo AU - Zha, Shan AU - Lan, Li AU - Liang, Huanhuan AU - Xu, Dongyi PY - 2015 DA - 2015/02/11 TI - Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway JO - Nature Communications SP - 6233 VL - 6 IS - 1 AB - Non-homologous end joining (NHEJ) is a major pathway to repair DNA double-strand breaks (DSBs), which can display different types of broken ends. However, it is unclear how NHEJ factors organize to repair diverse types of DNA breaks. Here, through systematic analysis of the human NHEJ factor interactome, we identify PAXX as a direct interactor of Ku. The crystal structure of PAXX is similar to those of XRCC4 and XLF. Importantly, PAXX-deficient cells are sensitive to DSB-causing agents. Moreover, epistasis analysis demonstrates that PAXX functions together with XLF in response to ionizing radiation-induced complex DSBs, whereas they function redundantly in response to Topo2 inhibitor-induced simple DSBs. Consistently, PAXX and XLF coordinately promote the ligation of complex but not simple DNA ends in vitro. Altogether, our data identify PAXX as a new NHEJ factor and provide insight regarding the organization of NHEJ factors responding to diverse types of DSB ends. SN - 2041-1723 UR - https://doi.org/10.1038/ncomms7233 DO - 10.1038/ncomms7233 ID - Xing2015 ER -