論文

査読有り
2017年6月

RFWD3-Mediated Ubiquitination Promotes Timely Removal of Both RPA and RAD51 from DNA Damage Sites to Facilitate Homologous Recombination

MOLECULAR CELL
  • Shojiro Inano
  • ,
  • Koichi Sato
  • ,
  • Yoko Katsuki
  • ,
  • Wataru Kobayashi
  • ,
  • Hiroki Tanaka
  • ,
  • Kazuhiro Nakajima
  • ,
  • Shinichiro Nakada
  • ,
  • Hiroyuki Miyoshi
  • ,
  • Kerstin Knies
  • ,
  • Akifumi Takaori-Kondo
  • ,
  • Detlev Schindler
  • ,
  • Masamichi Ishiai
  • ,
  • Hitoshi Kurumizaka
  • ,
  • Minoru Takata

66
5
開始ページ
622
終了ページ
+
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.molcel.2017.04.022
出版者・発行元
CELL PRESS

RFWD3 is a recently identified Fanconi anemia protein FANCW whose E3 ligase activity toward RPA is essential in homologous recombination (HR) repair. However, how RPA ubiquitination promotes HR remained unknown. Here, we identified RAD51, the central HR protein, as another target of RFWD3. We show that RFWD3 polyubiquitinates both RPA and RAD51 in vitro and in vivo. Phosphorylation by ATR and ATM kinases is required for this activity in vivo. RFWD3 inhibits persistent mitomycin C (MMC)-induced RAD51 and RPA foci by promoting VCP/p97-mediated protein dynamics and subsequent degradation. Furthermore, MMC-induced chromatin loading of MCM8 and RAD54 is defective in cells with inactivated RFWD3 or expressing a ubiquitination-deficient mutant RAD51. Collectively, our data reveal a mechanism that facilitates timely removal of RPA and RAD51 from DNA damage sites, which is crucial for progression to the late-phase HR and suppression of the FA phenotype.

Web of Science ® 被引用回数 : 67

リンク情報
DOI
https://doi.org/10.1016/j.molcel.2017.04.022
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28575658
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000402726700006&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.molcel.2017.04.022
  • ISSN : 1097-2765
  • eISSN : 1097-4164
  • PubMed ID : 28575658
  • Web of Science ID : WOS:000402726700006

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