2. Academic Validation
  3. Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway

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

  • Nat Commun. 2015 Feb 11;6:6233. doi: 10.1038/ncomms7233.
Mengtan Xing 1,  Mingrui Yang 2,  Wei Huo 1,  Feng Feng 3,  Leizhen Wei 4,  Wenxia Jiang 5,  Shaokai Ning 1,  Zhenxin Yan 1,  Wen Li 1,  Qingsong Wang 1,  Mei Hou 1,  Chunxia Dong 1,  Rong Guo 1,  Ge Gao 1,  Jianguo Ji 1,  Shan Zha 5,  Li Lan 4,  Huanhuan Liang 3,  Dongyi Xu 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 5 Yiheyuan Road, Beijing 100871, China.
  • 2 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.
  • 3 State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • 4 Department of Microbiology and Molecular Genetics, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Pittsburgh, Pennsylvania 15213, USA.
  • 5 Institute for Cancer Genetics, Columbia University Medical Center, New York City, New York 10032, USA.
PMID: 25670504 DOI: 10.1038/ncomms7233
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.

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