Analysis of pseudo transcription formation following transcription remodeling leading to homologous recombination repair

• Project/Area Number: 26701005
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Gunma University
• Principal Investigator: Shibata Atsushi 群馬大学, 大学院医学系研究科, 助教 (30707633)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥24,440,000 (Direct Cost: ¥18,800,000、Indirect Cost: ¥5,640,000); Fiscal Year 2016: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2015: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2014: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
• Keywords: DNA修復 / Homologous recombination / NHEJ / クロマチン / 転写

Outline of Final Research Achievements

Ionizing irradiation causes DNA double strand breaks, which can lead to cell death if unrepaired or misrepaired. In the present study, to identify a novel factor promoting HR at the step of DSB end resection, we carried out a screening experiment. Importantly, our analysis demonstrated that novel HR factors, MEC1 and REC1, which are originally involved in transcription, promote the initiation of HR by activating the step of DSB end resection. This finding provides us important information regarding the maintenance of genome stability after ionizing irradiation.

Research Products

• [Int'l Joint Research] サセックス大学(イギリス)
• [Int'l Joint Research] ダーマシュタット工科大学(ドイツ)
• [Journal Article] 3D-structured illumination microscopy reveals clustered DNA double-strand break formation in widespread γH2AX foci after high LET heavy-ion particle radiation (2017)
  • Author(s): Hagiwara Yoshihiko、Niimi Atsuko、Isono Mayu、Yamauchi Motohiro、Yasuhara Takaaki、Limsirichaikul Siripan、Oike Takahiro、Sato Hiro、Held Kathryn D.、Nakano Takashi、Shibata Atsushi
  • Journal Title: Oncotarget Volume: 8 Pages: 109370-109381
  • DOI: 10.18632/oncotarget.22679
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells. (2017)
  • Author(s): Sato Hiro、Niimi Atsuko、Yasuhara Takaaki、Permata Tiara Bunga Mayang、Hagiwara Yoshihiko、Isono Mayu、Nuryadi Endang、Sekine Ryota、Oike Takahiro、Kakoti Sangeeta、Yoshimoto Yuya、Held Kathryn D.、Suzuki Yoshiyuki、Kono Koji、Miyagawa Kiyoshi、Nakano Takashi、Shibata Atsushi
  • Journal Title: Nature Communications Volume: 8 Pages: 1751-1751
  • DOI: 10.1038/s41467-017-01883-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Regulation of repair pathway choice at two-ended DNA double-strand breaks (2017)
  • Author(s): Shibata Atsushi
  • Journal Title: Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis Volume: 803-805 Pages: 51-55
  • DOI: 10.1016/j.mrfmmm.2017.07.011
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Inhibition of the HDAC/Suv39/G9a pathway restores the expression of DNA damage-dependent major histocompatibility complex class I-related chain A and B in cancer cells (2017)
  • Author(s): Nakajima Nakako Izumi、Niimi Atsuko、Isono Mayu、Oike Takahiro、Sato Hiro、Nakano Takashi、Shibata Atsushi
  • Journal Title: Oncology Reports Volume: 38 Pages: 693-702
  • DOI: 10.3892/or.2017.5773
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mitotic catastrophe is a putative mechanism underlying the weak correlation between sensitivity to carbon ions and cisplatin. (2017)
  • Author(s): Kobayashi D, Oike T, Shibata A, Niimi A, Kubota Y, Sakai M, Amornwhichet N, Yoshimoto Y, Hagiwara Y, Kimura Y, Hirota Y, Sato H, Isono M, Yoshida Y, Kohno T, Ohno T, Nakano T
  • Journal Title: Sci Rep. Volume: 7 Pages: 40588-40588
  • DOI: 10.1038/srep40588
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Regulation of pairing between broken DNA-containing chromatin regions by Ku80, DNA-PKcs, ATM, and 53BP1. (2017)
  • Author(s): Motohiro Yamauchi, Atsushi Shibata, Keiji Suzuki, Masatoshi Suzuki, Atsuko Niimi, Hisayoshi Kondo, Miwa Miura, Miyako Hirakawa, Keiko Tsujita, Shunichi Yamashita, Naoki Matsuda
  • Journal Title: Sci Rep Volume: 7 Pages: 41812-41812
  • DOI: 10.1038/srep41812
  • NAID: 120006221100
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] DNA Double-Strand Break Resection Occurs during Non-homologous End Joining in G1 but Is Distinct from Resection during Homologous Recombination. (2017)
  • Author(s): Ronja Biehs, Monika Steinlage, Olivia Barton, Szilvia Juhasz, Julia Kunzel, Julian Spies, Atsushi Shibata, Penny Jeggo and Markus Lobrich.
  • Journal Title: MOLECULAR CELL Volume: 65(4)
  • DOI: 10.1016/j.molcel.2016.12.016
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] BRCA1 Directs the Repair Pathway to Homologous Recombination by Promoting 53BP1 Dephosphorylation (2017)
  • Author(s): Mayu Isono, Atsuko Niimi, Takahiro Oike, Yoshihiko Hagiwara, Hiro Sato, Ryota Sekine, Yukari Yoshida, Shin-Ya Isobe, Chikashi Obuse, Ryotaro Nishi, Elena Petricci, Shinichiro Nakada, Takashi Nakano, Atsushi Shibata
  • Journal Title: Cell Rep. Volume: 18 Pages: 520-532
  • DOI: 10.1016/j.celrep.2016.12.042
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] miR-137 Regulates the Tumorigenicity of Colon Cancer Stem Cells through the inhibition of DCLK1 (2017)
  • Author(s): Matsushita, K., Tamura, M., Tanaka, N., Tomonaga, T., Matsubara, H., Shimada, H., Levens, D., He, L., Liu, J., Yoshida, M., and Nomura, F
  • Journal Title: Molecular Cancerh Research Volume: 11 Pages: 354-362
  • Peer Reviewed / Open Access
• [Journal Article] Identification of DNA double strand breaks at chromosome boundaries along the track of particle irradiation. (2016)
  • Author(s): Atsuko Niimi, Motohiro Yamauchi, Siripan Limsirichaikul, Ryota Sekine, Takahiro Oike, Hiro Sato, Keiji Suzuki, Kathryn D. Held, Takashi Nakano, Atsushi Shibata
  • Journal Title: Genes, Chromosomes and Cancer Volume: 55 Pages: 650-60
  • DOI: 10.1002/gcc.22367
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Visualization of complex DNA double-strand breaks in a tumor treated with carbon ion radiotherapy (2016)
  • Author(s): Takahiro Oike, Atsuko Niimi, Noriyuki Okonogi, Kazutoshi Murata, Akihiko Matsumura, Shin-Ei Noda, Daijiro Kobayashi, Mototaro Iwanaga, Keisuke Tsuchida, Tatsuaki Kanai, Tatsuya Ohno, Atsushi Shibata, Takashi Nakano
  • Journal Title: Sci Rep Volume: 6 Pages: 22275-22275
  • DOI: 10.1038/srep22275
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Carbon-ion beams effectively induce growth inhibition and apoptosis in human neural stem cells compared with glioblastoma A172 cells (2015)
  • Author(s): Isono M, Yoshida Y, Takahashi A, Oike T, Shibata A, Kubota Y, Kanai T, Ohno T, Nakano T.
  • Journal Title: J Radiat Res Volume: 56 Pages: 856-861
  • DOI: 10.1093/jrr/rrv033
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The EGFR mutation status affects the relative biological effectiveness of carbon-ion beams in non-small cell lung carcinoma cells (2015)
  • Author(s): Amornwichet N, Oike T, Shibata A, Nirodi CS, Ogiwara H, Makino H, Kimura Y, Hirota Y, Isono M, Yoshida Y, Ohno T, Kohno T, Nakano T.
  • Journal Title: Scientific Reports Volume: 11 Pages: 11305-11305
  • DOI: 10.1038/srep11305
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Other Determinants of Sensitivity (2015)
  • Author(s): Naoyuki Okita and Atsushi Shibata
  • Journal Title: PARP Inhibitors for Cancer Therapy Volume: 83 Pages: 363-379
  • DOI: 10.1007/978-3-319-14151-0_15
  • Peer Reviewed
• [Journal Article] SETDB1, HP1 and SUV39 promote repositioning of 53BP1 to extend resection during homologous recombination in G2 cells. (2015)
  • Author(s): Meryem Alagoz, Yoko Katsuki, Hideaki Ogiwara, Tomoo Ogi, Atsushi Shibata, Andreas Kakarougkas, and Penny Jeggo
  • Journal Title: Nucleic Acids Res. Volume: 43(16) Pages: 7931-7944
  • DOI: 10.1093/nar/gkv722
  • NAID: 120005661530
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] "Pre-Exposure to Ionizing Radiation Stimulates DNA Double Strand Break End Resection, Promoting the Use of Homologous Recombination Repair" (2015)
  • Author(s): Nakako Izumi Nakajima, Yoshihiko Hagiwara, Takahiro Oike, Ryuichi Okayasu, Takeshi Murakami, Takashi Nakano, and Atsushi Shibata
  • Journal Title: PLOS ONE Volume: 10
  • DOI: 10.1371/journal.pone.0122582
  • Peer Reviewed / Open Access
• [Journal Article] DNA double-strand break repair in a cellular context (2014)
  • Author(s): Atsushi Shibata, Penny A. Jeggo
  • Journal Title: Clin Oncol (R Coll Radiol) Volume: 26 Pages: 243-249
  • DOI: 10.1016/j.clon.2014.02.004
  • Peer Reviewed
• [Journal Article] Carbon-ion beam irradiation kills X-ray-resistant p53-null cancer cells by inducing mitotic catastrophe (2014)
  • Author(s): Amornwichet N, Oike T, Shibata A, Ogiwara H, Tsuchiya N, Yamauchi M, Saitoh Y, Sekine R, Isono M, Yoshida Y, Ohno T, Kohno T, Nakano T
  • Journal Title: PLOS ONE Volume: 9
  • DOI: 10.1371/journal.pone.0115121
  • NAID: 120005527918
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells (2018)
  • Author(s): Atsushi Shibata
  • Organizer: Radiation Break-through: from DNA damage responses to precision cancer therapy
  • Int'l Joint Research
• [Presentation] Regulation of DSB repair pathway choice after ionizing radiation (2017)
  • Author(s): Atsushi Shibata
  • Organizer: 1st International Symposium on Radiation Therapeutics and Biology
  • Int'l Joint Research / Invited
• [Presentation] BRCA1 directs the repair pathway to homologous recombination by promoting 53BP1 dephosphorylation (2017)
  • Author(s): Atsushi Shibata
  • Organizer: IPR seminar on Chromosome Dynamic and genome stability in meiosis and mitosis
  • Int'l Joint Research / Invited
• [Presentation] 放射線・免疫治療併用を目指したがん免疫治療標的分子PD-L1発現調節機構の研究 (2017)
  • Author(s): 柴田 淳史
  • Organizer: 茨城大学理学部公開シンポジウム第11回Quantum medicine研究会
  • Invited
• [Presentation] DNA損傷シグナルによる免疫チェックポイント標的分子PD-L1の発現制御機構 (2017)
  • Author(s): 柴田 淳史
  • Organizer: 長崎大学 56回大学院セミナー・第89回原研研究集会
  • Invited
• [Presentation] DNA二本鎖切断修復経路による免疫チェックポイント標的分子PD-L1の発現制御機構 (2017)
  • Author(s): 柴田 淳史
  • Organizer: 2017年度 生命科学系学会合同年次大会（第４０回日本分子生物学会年会・第９０回日本生化学会大会）
  • Invited
• [Presentation] DNA二本鎖切断修復経路による免疫チェックポイント標的分子PD-L1の発現制御機構 (2017)
  • Author(s): 柴田 淳史
  • Organizer: 第24回DNA複製・組換え・修復ワークショップ
  • Invited
• [Presentation] DNA二本鎖切断修復の経路選択性とその変化に伴う細胞応答制御 (2017)
  • Author(s): 柴田 淳史
  • Organizer: 基礎生物学研究所セミナー
  • Invited
• [Presentation] 炭素イオン線が誘発するDNA二本鎖切断とその修復機構 (2017)
  • Author(s): 柴田 淳史
  • Organizer: 第６０回放射線影響学会
  • Invited
• [Presentation] 転写と共役するDNA二本鎖切断修復機構の解析 (2017)
  • Author(s): 柴田 淳史
  • Organizer: 国立遺伝学研究所・研究集会「染色体構築と安定化を担う分子機構」
  • Invited
• [Presentation] DNA repair pathway regulates PD-L1 expression in cancer cells. (2017)
  • Author(s): 柴田淳史
  • Organizer: International Symposium on Immune Diversity and Cancer Therapy Kobe 2017
  • Place of Presentation: 神戸ポートピアホテル(兵庫県・神戸市)
  • Year and Date: 2017-01-26
  • Int'l Joint Research
• [Presentation] DNA二本鎖切断修復経路の選択性を担う時空間的制御機構. (2016)
  • Author(s): 柴田淳史
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県・横浜市)
  • Year and Date: 2016-11-30
• [Presentation] 重粒子線特異的なDNA 損傷の可視化と修復経路への影響 (2016)
  • Author(s): 柴田淳史
  • Organizer: 放射線医学総合研究の第２回放射線がん生物研究セミナー
  • Place of Presentation: 放射線医学総合研究所(千葉県・千葉市)
  • Year and Date: 2016-11-15
  • Invited
• [Presentation] シンポジウム「多彩な細胞応答を制御する DNA 修復研究の最先端」（座長） (2016)
  • Author(s): 柴田淳史
  • Organizer: 日本放射線影響学会第59回大会
  • Place of Presentation: ＪＭＳアステールプラザ(広島県・広島市)
  • Year and Date: 2016-10-26
• [Presentation] DNA 二本鎖切断修復経路を制御するDNA end resection の多段階調 (2016)
  • Author(s): 柴田淳史
  • Organizer: 遺伝研研究集会「生物ゲノム安定維持の分子機構」
  • Place of Presentation: 国立遺伝学研究所(静岡県・三島市)
  • Year and Date: 2016-10-24
  • Invited
• [Presentation] BRCA1 directs the repair pathway to homologous recombination by promoting 53BP1 dephosphorylation (2016)
  • Author(s): 柴田淳史
  • Organizer: The 32th International Symposium “Growing Edge of Radiation Biology, from principles to applications”
  • Place of Presentation: ホテルコープイン京都(京都府・京都市)
  • Year and Date: 2016-09-01
  • Int'l Joint Research / Invited
• [Presentation] BRCA1 directs the repair pathway to homologous recombination by promoting 53BP1 dephosphorylation. (2016)
  • Author(s): 柴田淳史
  • Organizer: Abcam Conference “Mechanisms of Recombination”,
  • Place of Presentation: アリカンテ(スペイン)
  • Year and Date: 2016-05-19
  • Int'l Joint Research
• [Presentation] Analysis of cluster and DNA double strand break after heavy ion irradiation using high resolution microscopy (2016)
  • Author(s): 柴田淳史
  • Organizer: 14th International Workshop on Radiation Damage to DNA
  • Place of Presentation: メルボルン(オーストラリア)
  • Year and Date: 2016-03-21
  • Int'l Joint Research
• [Presentation] DNA修復研究からの放射線治療発展へのアプローチ (2016)
  • Author(s): 柴田淳史
  • Organizer: 茨城大学理学部公開シンポジウム 「第9回 Quantum Medicine 研究会」
  • Place of Presentation: 茨城大学理学部(茨城県・水戸市)
  • Year and Date: 2016-03-13
  • Invited
• [Presentation] DNA二本鎖切断修復経路を決定する時空間的制御機構の解明 (2015)
  • Author(s): 柴田淳史
  • Organizer: 放射線医学総合研究所・第７回次世代放射線治療研究セミナー「DNA修復の最先端」
  • Place of Presentation: 放射線医学総合研究所(千葉県・千葉市)
  • Year and Date: 2015-12-18
  • Invited
• [Presentation] 多様なDNA損傷応答の統合制御機構２０１５ ~ゲノム不安定性の病態解明研究~ (2015)
  • Author(s): 柴田淳史
  • Organizer: 第38回 日本分子生物学会・第88回日本生化学会 合同大会
  • Place of Presentation: 神戸ポートピアホテル 本館 B1F 偕楽1(兵庫県・神戸市)
  • Year and Date: 2015-12-03
• [Presentation] Understanding the molecular mechanism for developing a novel treatment strategy in radiotherapy (2015)
  • Author(s): 柴田淳史
  • Organizer: 日本放射線腫瘍学会第２８回大会
  • Place of Presentation: 前橋商工会議所 サクラ(群馬県・前橋市)
  • Year and Date: 2015-11-19
  • Invited
• [Presentation] BRCA1によるDNA end resectionの調節機構の解明 (2015)
  • Author(s): 柴田淳史
  • Organizer: 国立遺伝学研究所・研究集会「染色体DNAの安定維持の分子メカニズム」
  • Place of Presentation: 国立遺伝学研究所・講堂(静岡県・三島市)
  • Year and Date: 2015-10-01
  • Invited
• [Presentation] District regulation of DNA double strand break resection after heavy ion irradiation (2015)
  • Author(s): 柴田淳史
  • Organizer: The 2015 IMB conference, DNA Repair & Genome Stability in a Chromatin Environment
  • Place of Presentation: マインツ(ドイツ)
  • Year and Date: 2015-06-04
  • Int'l Joint Research
• [Presentation] Initiation of homologous recombination repair by MRE11 nuclease activities (2015)
  • Author(s): Atsushi Shibata
  • Organizer: Genomic Instability and DNA Repair (X4)
  • Place of Presentation: Whistler Conference Centre (Canada, Whistler, British Columbia)
  • Year and Date: 2015-03-04
• [Presentation] DNA二本鎖切断修復経路を決定する分子メカニズム (2014)
  • Author(s): 柴田淳史
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-11-27
• [Presentation] DNA二本鎖切断発生後の相同組換え修復開始メカニズム (2014)
  • Author(s): 柴田淳史
  • Organizer: 国立遺伝学研究所・研究集会「染色体DNAの安定維持の分子メカニズム」
  • Place of Presentation: 国立遺伝学研究所・講堂（静岡県・三島市）
  • Year and Date: 2014-11-06
  • Invited
• [Presentation] DNA二本鎖切断修復経路を決定する分子メカニズム (2014)
  • Author(s): 柴田淳史
  • Organizer: 日本放射線影響学会第57回大会
  • Place of Presentation: かごしま県民交流センター（鹿児島県・鹿児島市）
  • Year and Date: 2014-10-03
  • Invited
• [Presentation] 放射線誘発DNA二本鎖切断発生後の修復経路決定メカニズム (2014)
  • Author(s): 柴田淳史
  • Organizer: 人材育成事業第1回集中講義「放射線の生体効果：発ガン誘導と抵抗性獲得メカニズム」
  • Place of Presentation: 京都大学原子炉実験所 会議室（大阪府・泉南郡）
  • Year and Date: 2014-08-10
  • Invited
• [Presentation] DNA二本鎖切断修復経路決定に関わる分子機構の解明 (2014)
  • Author(s): 柴田淳史
  • Organizer: Genome Damage Network Workshop in Tohoku University 2014
  • Place of Presentation: 東北大学 加齢医学研究所（宮城県・仙台市）
  • Year and Date: 2014-06-05 – 2014-06-06
  • Invited
• [Presentation] Initiation of homologous recombination repair by MRE11 nuclease activities (2014)
  • Author(s): Atsushi Shibata
  • Organizer: Mechanisms of Recombination:50th Anniversary Meeting of the Holliday Model
  • Place of Presentation: Melia Alicante (Spain, Alicante)
  • Year and Date: 2014-05-19 – 2014-05-23
• [Presentation] 放射線照射後のDNA二本鎖切断修復とチェックポイントシグナル研究 (2014)
  • Author(s): 柴田淳史
  • Organizer: 第18回NRGIC重点セミナー/第18回原研研究集会 がんプロフェッショナル養成基盤推進プラン講演会
  • Place of Presentation: 長崎大学（長崎県・長崎市）
  • Year and Date: 2014-04-25
  • Invited
• [Presentation] 欠失及び転座を導くG1(G0)期細胞のDSB end resection機構 (2014)
  • Author(s): 柴田淳史
  • Organizer: 浜名湖ワークショップ
  • Place of Presentation: 浜名湖弁天リゾート ジ・オーシャン（静岡県・浜松市）
  • Year and Date: 2014-04-03 – 2014-04-04
• [Remarks] DNA修復研究 柴田研究室
  • URL: http://shibatalab.com/
• [Remarks] SHIBATA LAB
  • URL: http://shibatalab.com/english/
• [Remarks] DNA修復研究 柴田研究室
  • URL: http://shibatalab.com
• [Remarks] SHIBATA LAB
  • URL: http://shibatalab.com/english
• [Remarks] 先端科学研究指導者育成ユニット
  • URL: http://asrldu.dept.med.gunma-u.ac.jp