論文

査読有り
2017年12月

The CDK-PLK1 axis targets the DNA damage checkpoint sensor protein RAD9 to promote cell proliferation and tolerance to genotoxic stress

ELIFE
  • Takeshi Wakida
  • ,
  • Masae Ikura
  • ,
  • Kenji Kuriya
  • ,
  • Shinji Ito
  • ,
  • Yoshiharu Shiroiwa
  • ,
  • Toshiyuki Habu
  • ,
  • Takuo Kawamoto
  • ,
  • Katsuzumi Okumura
  • ,
  • Tsuyoshi Ikura
  • ,
  • Kanji Furuya

6
開始ページ
:e29953
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.7554/eLife.29953
出版者・発行元
ELIFE SCIENCES PUBLICATIONS LTD

Genotoxic stress causes proliferating cells to activate the DNA damage checkpoint, to assist DNA damage recovery by slowing cell cycle progression. Thus, to drive proliferation, cells must tolerate DNA damage and suppress the checkpoint response. However, the mechanism underlying this negative regulation of checkpoint activation is still elusive. We show that human Cyclin-Dependent-Kinases (CDKs) target the RAD9 subunit of the 9-1-1 checkpoint clamp on Thr292, to modulate DNA damage checkpoint activation. Thr292 phosphorylation on RAD9 creates a binding site for Polo-Like-Kinase1 (PLK1), which phosphorylates RAD9 on Thr313. These CDK-PLK1-dependent phosphorylations of RAD9 suppress checkpoint activation, therefore maintaining high DNA synthesis rates during DNA replication stress. Our results suggest that CDK locally initiates a PLK1-dependent signaling response that antagonizes the ability of the DNA damage checkpoint to detect DNA damage. These findings provide a mechanism for the suppression of DNA damage checkpoint signaling, to promote cell proliferation under genotoxic stress conditions.

Web of Science ® 被引用回数 : 7

リンク情報
DOI
https://doi.org/10.7554/eLife.29953
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000418225300001&DestApp=WOS_CPL

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