@article{oai:repo.qst.go.jp:00079986,
 author = {Nakajima, Nakako and Yamauchi, Motohiro and Kakoti, Sangeeta and Liu, Cuihua and Kato, Reona and Tiara Bunga Mayang Permata and Iijima, Moito and Yajima, Hirohiko and Yasuhara, Takaaki and Yamada, Shigeru and Hasegawa, Sumitaka and Shibata, Atsushi and Nakajima, Nakako and Liu, Cuihua and Iijima, Moito and Yajima, Hirohiko and Yamada, Shigeru and Hasegawa, Sumitaka and Shibata, Atsushi},
 journal = {DNA Repair},
 month = {Jul},
 note = {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.},
 title = {RNF8 promotes high linear energy transfer carbon-ion-induced DNA double-stranded break repair in serum-starved human cells},
 volume = {91-92},
 year = {2020}
}