論文

査読有り
2018年4月

Replication stress induces accumulation of FANCD2 at central region of large fragile genes

NUCLEIC ACIDS RESEARCH
  • Yusuke Okamoto
  • ,
  • Watal M. Iwasaki
  • ,
  • Kazuto Kugou
  • ,
  • Kazuki K. Takahashi
  • ,
  • Arisa Oda
  • ,
  • Koichi Sato
  • ,
  • Wataru Kobayashi
  • ,
  • Hidehiko Kawai
  • ,
  • Ryo Sakasai
  • ,
  • Akifumi Takaori-Kondo
  • ,
  • Takashi Yamamoto
  • ,
  • Masato T. Kanemaki
  • ,
  • Masato Taoka
  • ,
  • Toshiaki Isobe
  • ,
  • Hitoshi Kurumizaka
  • ,
  • Hideki Innan
  • ,
  • Kunihiro Ohta
  • ,
  • Masamichi Ishiai
  • ,
  • Minoru Takata

46
6
開始ページ
2932
終了ページ
2944
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1093/nar/gky058
出版者・発行元
OXFORD UNIV PRESS

During mild replication stress provoked by low dose aphidicolin (APH) treatment, the key Fanconi anemia protein FANCD2 accumulates on common fragile sites, observed as sister foci, and protects genome stability. To gain further insights into FANCD2 function and its regulatory mechanisms, we examined the genome-wide chromatin localization of FANCD2 in this setting by ChIP-seq analysis. We found that FANCD2 mostly accumulates in the central regions of a set of large transcribed genes that were extensively overlapped with known CFS. Consistent with previous studies, we found that this FANCD2 retention is R-loop-dependent. However, FANCD2 monoubiquitination and RPA foci formation were still induced in cells depleted of R-loops. Interestingly, we detected increased Proximal Ligation Assay dots between FANCD2 and R-loops following APH treatment, which was suppressed by transcriptional inhibition. Collectively, our data suggested that R-loops are required to retain FANCD2 in chromatin at the middle intronic region of large genes, while the replication stress-induced upstream events leading to the FA pathway activation are not triggered by R-loops.

Web of Science ® 被引用回数 : 27

リンク情報
DOI
https://doi.org/10.1093/nar/gky058
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29394375
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000429009500022&DestApp=WOS_CPL
ID情報
  • DOI : 10.1093/nar/gky058
  • ISSN : 0305-1048
  • eISSN : 1362-4962
  • PubMed ID : 29394375
  • Web of Science ID : WOS:000429009500022

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