論文

査読有り
2016年3月

In cellulo phosphorylation of XRCC4 Ser320 by DNA-PK induced by DNA damage

JOURNAL OF RADIATION RESEARCH
  • Mukesh Kumar Sharma
  • ,
  • Shoji Imamichi
  • ,
  • Mikoto Fukuchi
  • ,
  • Ravindra Mahadeo Samarth
  • ,
  • Masanori Tomita
  • ,
  • Yoshihisa Matsumoto

57
2
開始ページ
115
終了ページ
120
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1093/jrr/rrv086
出版者・発行元
OXFORD UNIV PRESS

XRCC4 is a protein associated with DNA Ligase IV, which is thought to join two DNA ends at the final step of DNA double-strand break repair through non-homologous end joining. In response to treatment with ionizing radiation or DNA damaging agents, XRCC4 undergoes DNA-PK-dependent phosphorylation. Furthermore, Ser260 and Ser320 (or Ser318 in alternatively spliced form) of XRCC4 were identified as the major phosphorylation sites by purified DNA-PK in vitro through mass spectrometry. However, it has not been clear whether these sites are phosphorylated in vivo in response to DNA damage. In the present study, we generated an antibody that reacts with XRCC4 phosphorylated at Ser320 and examined in cellulo phosphorylation status of XRCC4 Ser320. The phosphorylation of XRCC4 Ser320 was induced by gamma-ray irradiation and treatment with Zeocin. The phosphorylation of XRCC4 Ser320 was detected even after 1 Gy irradiation and increased in a manner dependent on radiation dose. The phosphorylation was observed immediately after irradiation and remained mostly unchanged for up to 4 h. The phosphorylation was inhibited by DNA-PK inhibitor NU7441 and was undetectable in DNA-PKcs-deficient cells, indicating that the phosphorylation was mainly mediated by DNA-PK. These results suggested potential usefulness of the phosphorylation status of XRCC4 Ser320 as an indicator of DNA-PK functionality in living cells.

Web of Science ® 被引用回数 : 8

リンク情報
DOI
https://doi.org/10.1093/jrr/rrv086
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000372619800003&DestApp=WOS_CPL

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