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The complexity of DNA double strand break is a crucial factor for activating ATR signaling pathway for G2/M checkpoint regulation regardless of ATM function
https://repo.qst.go.jp/records/47039
https://repo.qst.go.jp/records/47039a3b7e705-cc7f-4a06-a991-340d90b2a572
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2015-02-20 | |||||
| タイトル | ||||||
| タイトル | The complexity of DNA double strand break is a crucial factor for activating ATR signaling pathway for G2/M checkpoint regulation regardless of ATM function | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Xue, Lian
× Xue, Lian× Furusawa, Yoshiya× Okayasu, Ryuichi× Miura, Masahiko× Cui, Xing× Liu, Cuihua× Hirayama, Ryoichi× Matsumoto, Yoshitaka× Yajima, Hirohiko× Yu, Dong× 薛 蓮× 古澤 佳也× 岡安 隆一× 三浦 雅彦× 崔 星× 劉 翠華× 平山 亮一× 松本 孔貴× 矢島 浩彦× 于 冬 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | DNA double strand break (DSB) repair pathway choice following ionizing radiation (IR) is currently an appealing research topic, which is still largely unclear. Our recent paper indicated that the complexity of DSBs is a critical factor that enhances DNA end resection. It has been well accepted that the RPA-coated single strand DNA produced by resection is a signaling structure for ATR activation. Therefore, taking advantage of high linear energy transfer (LET) radiation to effectively produce complex DSBs, we investigated how the complexity of DSB influences the function of ATR pathway on the G2/M checkpoint regulation. Human skin fibroblast cells with or without ATM were irradiated with X rays or heavy ion particles, and dual-parameter flow cytometry was used to quantitatively assess the mitotic entry at early period post radiation by detecting the cells positive for phosphor histone H3. In ATM-deficient cells, ATR pathway played a pivotal role and functioned in a dose- and LET-dependent way to regulate the early G2/M arrest even as low as 0.2 Gy for heavy ion radiation, which indicated that ATR pathway could be rapidly activated and functioned in an ATM-independent, but DSB complexity-dependent manner following exposure to IR. Furthermore, ATR pathway also functioned more efficiently in ATM-proficient cells to block G2 to M transition at early period of IR. Accordingly, in contrast to ATM inhibitor, ATR inhibitor had a more effective radiosensitizing effect on survival fraction following heavy ion beams as compared with X ray radiation. Taken together, our results reveal that the complexity of DSBs is a crucial factor for the activation of ATR pathway for G2/M checkpoint regulation, and ATM-dependent end resection is not essential for the activation. | |||||
| 書誌情報 |
DNA repair 巻 25, p. 72-83, 発行日 2014-11 |
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| 出版者 | ||||||
| 出版者 | Elsevier | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1568-7864 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 25497328 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1016/j.dnarep.2014.11.004 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | http://www.sciencedirect.com/science/article/pii/S1568786414002791 | |||||
| 関連名称 | http://www.sciencedirect.com/science/article/pii/S1568786414002791 | |||||
