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タイトル: | Replication stress induces accumulation of FANCD2 at central region of large fragile genes |
著者: | Okamoto, Yusuke Iwasaki, Watal M Kugou, Kazuto Takahashi, Kazuki K Oda, Arisa Sato, Koichi Kobayashi, Wataru Kawai, Hidehiko Sakasai, Ryo Takaori-Kondo, Akifumi Yamamoto, Takashi Kanemaki, Masato T Taoka, Masato Isobe, Toshiaki Kurumizaka, Hitoshi Innan, Hideki Ohta, Kunihiro Ishiai, Masamichi Takata, Minoru https://orcid.org/0000-0002-4926-3675 (unconfirmed) |
著者名の別形: | 髙田, 穣 |
発行日: | 6-Apr-2018 |
出版者: | Oxford University Press (OUP) |
誌名: | Nucleic Acids Research |
巻: | 46 |
号: | 6 |
開始ページ: | 2932 |
終了ページ: | 2944 |
抄録: | 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. |
著作権等: | © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
URI: | http://hdl.handle.net/2433/232583 |
DOI(出版社版): | 10.1093/nar/gky058 |
PubMed ID: | 29394375 |
出現コレクション: | 学術雑誌掲載論文等 |
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