Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway

Mengtan Xing, Mingrui Yang, Wei Huo, Feng Feng, Leizhen Wei, Wenxia Jiang, Shaokai Ning, Zhenxin Yan, Wen Li, Qingsong Wang, Mei Hou, Chunxia Dong, Rong Guo, Ge Gao, Jianguo Ji, Shan Zha, Li Lan, Huanhuan Liang and Dongyi Xu ()
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Mengtan Xing: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
Mingrui Yang: State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Wei Huo: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
Feng Feng: State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Leizhen Wei: University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine
Wenxia Jiang: Institute for Cancer Genetics, Columbia University Medical Center
Shaokai Ning: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
Zhenxin Yan: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
Wen Li: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
Qingsong Wang: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
Mei Hou: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
Chunxia Dong: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
Rong Guo: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
Ge Gao: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
Jianguo Ji: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
Shan Zha: Institute for Cancer Genetics, Columbia University Medical Center
Li Lan: University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine
Huanhuan Liang: State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Dongyi Xu: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: Abstract 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.

Date: 2015
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DOI: 10.1038/ncomms7233

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