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RNF8 promotes high linear energy transfer carbon-ion-induced DNA double-stranded break repair in serum-starved human cells
https://repo.qst.go.jp/records/79986
https://repo.qst.go.jp/records/79986c8b596ed-0141-4303-87c8-fba0b66103cc
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2020-05-28 | |||||
| タイトル | ||||||
| タイトル | RNF8 promotes high linear energy transfer carbon-ion-induced DNA double-stranded break repair in serum-starved human cells | |||||
| 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 |
Nakajima, Nakako
× Nakajima, Nakako× Yamauchi, Motohiro× Kakoti, Sangeeta× Liu, Cuihua× Kato, Reona× Tiara Bunga Mayang Permata× Iijima, Moito× Yajima, Hirohiko× Yasuhara, Takaaki× Yamada, Shigeru× Hasegawa, Sumitaka× Shibata, Atsushi× Nakajima, Nakako× Liu, Cuihua× Iijima, Moito× Yajima, Hirohiko× Yamada, Shigeru× Hasegawa, Sumitaka× Shibata, Atsushi |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | The cell-killing effect of radiotherapy largely depends on unrepaired DNA double-stranded breaks (DSBs) or lethal chromosome aberrations induced by DSBs. Thus, the capability of DSB repair status is critically important in cancer cell-killing effect after ionizing radiation. Here, we investigate the involvement of the DNA damage signaling factors ataxia telangiectasia mutated (ATM) and ring finger protein (RNF) 8 and RNF168 in quiescent G0/G1 cells, which occupy the majority population in tumors, after high-linear-energy-transfer (LET) carbon-ion irradiation. Interestingly, ATM inhibition caused a substantial DSB repair defect after high-LET carbon-ion irradiation. Similarly, RNF8 or RNF168 depletion causes a substantial DSB repair defect. ATM inhibition in RNF8-depleted cells did not have an additive effect, suggesting that ATM and RNF8 function in the same pathway. Importantly, we found that RNF8 RING mutant show similar DSB repair defect, suggesting the requirement of ubiquitin ligase activity in this repair pathway. RNF8 FHA domain, which is required for the interaction with MDC1, is also required for DSB repair in this axis. Furthermore, depletion of p53 binding protein 1 (53BP1), which is an important downstream factor in RNF8-dependent DSB repair, is also required for this repair. Importantly, either ATM inhibition or RNF8 depletion increased the frequency of chromosomal breaks, but reduced dicentric chromosome formation, demonstrating that ATM/RNF8 is required for the rejoining of DSB ends for dicentric chromosome formation. Finally, we show that RNF8 depletion augmented radiosensitivity after high-LET carbon-ion irradiation. Taken together, these results suggest that the inhibition of RNF8 activity or its downstream pathway may augment the efficacy of high-LET carbon-ion therapy. | |||||
| 書誌情報 |
DNA Repair 巻 91-92, 発行日 2020-07 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1568-7864 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1016/j.dnarep.2020.102872 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.sciencedirect.com/science/article/pii/S1568786420301208 | |||||
