title: Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway.
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.
authors: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 5 Yiheyuan Road, Beijing 100871, China.
authors: Mengtan
authors: M
authors: Xing
authors: 1] State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [2] State Key Laboratory of Virology, School of Basic Medicine, Wuhan University, Wuhan 430071, China.
authors: Mingrui
authors: M
authors: Yang
authors: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 5 Yiheyuan Road, Beijing 100871, China.
authors: Wei
authors: W
authors: Huo
authors: State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Feng
authors: F
authors: Feng
authors: Department of Microbiology and Molecular Genetics, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Pittsburgh, Pennsylvania 15213, USA.
authors: Leizhen
authors: L
authors: Wei
authors: Institute for Cancer Genetics, Columbia University Medical Center, New York City, New York 10032, USA.
authors: Wenxia
authors: W
authors: Jiang
authors: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 5 Yiheyuan Road, Beijing 100871, China.
authors: Shaokai
authors: S
authors: Ning
authors: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 5 Yiheyuan Road, Beijing 100871, China.
authors: Zhenxin
authors: Z
authors: Yan
authors: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 5 Yiheyuan Road, Beijing 100871, China.
authors: Wen
authors: W
authors: Li
authors: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 5 Yiheyuan Road, Beijing 100871, China.
authors: Qingsong
authors: Q
authors: Wang
authors: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 5 Yiheyuan Road, Beijing 100871, China.
authors: Mei
authors: M
authors: Hou
authors: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 5 Yiheyuan Road, Beijing 100871, China.
authors: Chunxia
authors: C
authors: Dong
authors: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 5 Yiheyuan Road, Beijing 100871, China.
authors: Rong
authors: R
authors: Guo
authors: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 5 Yiheyuan Road, Beijing 100871, China.
authors: Ge
authors: G
authors: Gao
authors: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 5 Yiheyuan Road, Beijing 100871, China.
authors: Jianguo
authors: J
authors: Ji
authors: Institute for Cancer Genetics, Columbia University Medical Center, New York City, New York 10032, USA.
authors: Shan
authors: S
authors: Zha
authors: Department of Microbiology and Molecular Genetics, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Pittsburgh, Pennsylvania 15213, USA.
authors: Li
authors: L
authors: Lan
authors: State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Huanhuan
authors: H
authors: Liang
authors: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 5 Yiheyuan Road, Beijing 100871, China.
authors: Dongyi
authors: 0000000157112618
authors: D
authors: Xu
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D002460:Cell Line; D002645:Chickens; D018360:Crystallography, X-Ray; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D000072200:Ku Autoantigen; D013058:Mass Spectrometry; D008954:Models, Biological; D008958:Models, Molecular; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; C508551:NHEJ1 protein, human; C000595075:PAXX protein, human; C101467:XRCC4 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen; D011088:DNA Ligases; D045643:DNA Repair Enzymes; D000072481:DNA Ligase ATP