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FAN Ying-Jun,LIU Yu-Heng,WANG Yu-Lan,KONG Bing-Jie,ZHAO Yun,YE Chen,AN Li-Li,HANG Hai-Ying.Interaction of the checkpoint protein Rad9 and the non-homologous end-joining protein Ku70[J].Progress in Biochemistry and Biophysics
Interaction of the checkpoint protein Rad9 and the non-homologous end-joining protein Ku70
Received:June 11, 2018  Revised:August 16, 2018
Key words:Rad9, NHEJ, Ku70, DNA-PKcs
Fund:中国国家自然科学基金 (31370792),国家自然科学基金 (U1738112)
Author NameAffiliationE-mail
FAN Ying-Jun Key Laboratory for Protein and Peptide Pharmaceuticals, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, University of Chinese Academy of Sciences lightning_fan@163.com 
LIU Yu-Heng Key Laboratory for Protein and Peptide Pharmaceuticals, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, University of Chinese Academy of Sciences  
WANG Yu-Lan Key Laboratory for Protein and Peptide Pharmaceuticals, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, University of Chinese Academy of Sciences  
KONG Bing-Jie Key Laboratory for Protein and Peptide Pharmaceuticals, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, University of Chinese Academy of Sciences  
ZHAO Yun Key Laboratory for Protein and Peptide Pharmaceuticals, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences  
YE Chen Key Laboratory for Protein and Peptide Pharmaceuticals, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences  
AN Li-Li Key Laboratory for Protein and Peptide Pharmaceuticals, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences  
HANG Hai-Ying Key Laboratory for Protein and Peptide Pharmaceuticals, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences hh91@ibp.ac.cn 
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Abstract:
      Rad9 plays roles in both cell cycle checkpoint control and DNA repair. It can interact with the components of multiple DNA repair pathways and regulate their functions. Non-homologous end-joining (NHEJ) repair pathway is predominantly used in vertebrates for the repair of DNA double strand break (DSB). Proper activation of DNA-dependent protein kinase (DNA-PK), composed of Ku70, Ku80, and DNA-dependent protein kinase catalytic subunit (DNA-PKcs), is essential for NHEJ repair. In this study, we found that Rad9 interacts with Ku70 physically and functionally. Deletion of Rad9 gene, knockdown of Rad9 expression or removal of Rad9 protein led to inefficient DNA end-joining repair. Furthermore, loss of Rad9 impaired the DNA damage-induced binding of Ku70 to the chromatin and attenuated the DNA damage-induced kinase activity of DNA-PKcs. Taken together, our data unveil a novel functional interplay between Rad9 and the NHEJ protein Ku70, indicating a role of Rad9 in NHEJ repair through modulating the activation of the DNA-PKcs/Ku70/Ku80 complex.
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