Epigenetic regulation of cellular robustness in DNA damage response

• Project/Area Number: 15K12203
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Kyoto University
• Principal Investigator: Ikura Tsuyoshi 京都大学, 放射線生物研究センター, 准教授 (70335686)
• Co-Investigator(Renkei-kenkyūsha): MATSUDA Tomonari 京都大学, 工学研究科附属 流域圏総合環境質研究センター, 准教授 (50273488)
• Research Collaborator: IKURA Masae
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 放射線障害 / エピジェネティクス / TIP60 / アセチル化 / 細胞ロバストネス

Outline of Final Research Achievements

We investigated the mechanism of acquired radio-resistance in cells after gamma irradiation, focusing on histone modifications and protein networks via histone modifications around DNA damage sites. In order to clarify this, we performed chromatin immunoprecipitation (Chromatin IP) after infection I-Sce1 adenovirus, which produce DNA double-strand break, in the acquired radio-resistance HeLa/DR-GFP cells, using anti-histone H2AX acetylation, phosphorylation or histone H4 acetylation antibodies. As a result, no remarkable change of histone modifications was observed between the acquired radio-resistance and non-resistant HeLa/DR-GFP cells. We also analyzed DNA repair efficiency using HeLa/DR-GFP system between these cells. As a result, DNA repair efficiency in acquired radio-resistance HeLa/DR-GFP cells is comparable to that in non-resistant HeLa/DR-GFP cells.

Research Products

• [Journal Article] Xeroderma pigmentosum group C protein interacts with histones: Regulation by acetylated states of histone H3. (2017)
  • Author(s): Kakumu E
  • Journal Title: Genes Cells Volume: 3 Pages: 310-327
  • DOI: 10.1111/gtc.12479
  • NAID: 120006363283
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Histone H4 lysine 20 acetylation is associated with gene repression in human cells (2016)
  • Author(s): Kaimori, J. Y., Maehara, K., Hayashi-Takanaka, Y., Harada, A., Fukuda, M., Yamamoto, S., Ichimaru, N., Umehara, T., Yokoyama, S., Matsuda, R., Ikura, T., Nagao, K., Obuse, C., Nozaki, N., Takahara, S., Takao, T., Ohkawa, Y., Kimura, H., and Isaka, Y.
  • Journal Title: Scientific Reports Volume: 6 Pages: 24318-24318
  • DOI: 10.1038/srep24318
  • NAID: 120005770760
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Histone H2A T120 Phosphorylation Promotes Oncogenic Transformation via Upregulation of Cyclin D1 (2016)
  • Author(s): Aihara H
  • Journal Title: Mol Cell. Volume: 64 Pages: 176-188
  • DOI: 10.1016/j.molcel.2016.09.012
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Coordinated Regulation of TIP60 and Poly(ADP-Ribose) Polymerase 1 in Damaged-Chromatin Dynamics. (2016)
  • Author(s): Ikura M
  • Journal Title: Mol. Cel. Biol. Volume: Epub ahead of print Pages: 1595-1607
  • DOI: 10.1128/mcb.01085-15
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Disruption of DNA Damage-response by Propyl Gallate and 9-Aminoacridine (2016)
  • Author(s): Matsuda S
  • Journal Title: Toxicological Sciences Volume: 150 Pages: 1-12
  • DOI: 10.1093/toxsci/kfw039
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] SMARCAD1 is an ATP-dependent stimulator of nucleosomal H2A acetylation via CBP, resulting in transcriptional regulation (2016)
  • Author(s): Doiguchi M
  • Journal Title: Scientific reports Volume: 6 Pages: 20179-20179
  • DOI: 10.1038/srep20179
  • NAID: 120005819495
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Epigenetic Regulation of the Blimp-1 Gene (Prdm1) in B Cells Involves Bach2 and Histone Deacetylase 3 (2016)
  • Author(s): Tanaka H
  • Journal Title: Journal of Biological Chemistry Volume: 291 Pages: 6316-6330
  • DOI: 10.1074/jbc.m116.713842
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Nuclear pyruvate kinase M2 complex serves as a transcriptional coactivator of arylhydrocarbon receptor (2016)
  • Author(s): Shun Matsuda, Jun Adachi, Masaru Ihara, Nobuhiro Tanuma, Hiroshi Shima, Akira Kakizuka, Masae Ikura, Tsuyoshi Ikura, Tomonari Matsuda
  • Journal Title: Nucleic Acids Research Volume: 44(2) Pages: 636-647
  • DOI: 10.1093/nar/gkv967
  • NAID: 120005818255
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] SUMOylation of xeroderma pigmentosum group C protein regulates DNA damage recognition during nucleotide excision repair. (2016)
  • Author(s): Akita M
  • Journal Title: Sci Rep. Volume: 5 Pages: 10984-10984
  • DOI: 10.1038/srep10984
  • NAID: 120005621887
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Acetylation of Histone H2AX at Lys 5 by the TIP60 Histone Acetyltransferase Complex Is Essential for the Dynamic Binding of NBS1 to Damaged Chromatin (2015)
  • Author(s): Ikura M
  • Journal Title: Mol Cell Biol. Volume: 35 Pages: 4147-4157
  • DOI: 10.1128/mcb.00757-15
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Structural basis of a nucleosome containing histone H2A.B/H2A.Bbd that transiently associates with reorganized chromatin (2015)
  • Author(s): Arimura Y
  • Journal Title: Sci Rep. Volume: 5 Pages: 09628-09628
  • DOI: 10.1038/srep09628
  • Peer Reviewed / Open Access
• [Journal Article] hCAS/CSE1L regulates RAD51 distribution and focus formation for homologous recombinational repair. (2015)
  • Author(s): 1.Okimoto S, Sun J, Fukuto A, Horikoshi Y, Matsuda S, Matsuda T, Ikura M, Ikura T, Machida S, Kurumizaka H, Miyamoto Y, Oka M, Yoneda Y, Kiuchi Y, Tashiro S.
  • Journal Title: Genes Cells Volume: 20 Pages: 681-694
  • DOI: 10.1111/gtc.12262
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Absolute quantification of acetylation and phosphorylation of the histone variant H2AX upon ionizing radiation reveals distinct cellular responses in two cancer cell lines (2015)
  • Author(s): Matsuda S
  • Journal Title: Radiat Environ Biophys Volume: 54 Pages: 403-411
  • DOI: 10.1007/s00411-015-0608-3
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Absolute quantification of gammaH2AX using liquid chromatography-triple quadrupole tandem mass spectrometry (2015)
  • Author(s): Matsuda, S., Ikura, T., Matsuda, T.
  • Journal Title: Anal Bioanal Chem Volume: in press Pages: 5521-5527
  • DOI: 10.1007/s00216-015-8725-z
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] タンパク質複合体解析の現状と今後への挑戦 (2016)
  • Author(s): 井倉 毅
  • Organizer: 岡崎フラグメント50周年シンポジウム
  • Place of Presentation: 名古屋市
  • Year and Date: 2016-12-21
  • Invited
• [Presentation] ゲノムストレス応答の多様性を数理的アプローチで理解する (2016)
  • Author(s): 井倉 毅
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-11-30
• [Presentation] リンカーヒストンH1を含むクロマチンでの相同組換え反応 (2016)
  • Author(s): 町田晋一
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-11-30
• [Presentation] RAD51による相同組換え修復の制御機構 (2016)
  • Author(s): 堀越保則
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-11-30
• [Presentation] DNAチェックポイント因子Rad9の機能制御を担うCdk-Plk1依存的機構の意義 (2016)
  • Author(s): 郡司 未佳
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-11-30
• [Presentation] がん細胞で高頻度におこるヒストンH2B点変異体はヌクレオソーム構造および細胞増殖に影響を与える (2016)
  • Author(s): 野田真美子
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-11-30
• [Presentation] Molecular mechanism of etoposide induced 11q23 chromosome translocations. (2016)
  • Author(s): 孫 継英
  • Organizer: 日本放射線影響学会 第59回大会
  • Place of Presentation: 広島市
  • Year and Date: 2016-10-26
• [Presentation] がん研究入門コース1「がん研究におけるクロマチン生物学」 (2016)
  • Author(s): 井倉 毅
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-10-06
  • Invited
• [Presentation] DNA損傷応答におけるヒストンH2AX複合体モジュールのダイナミクス (2016)
  • Author(s): 井倉 毅
  • Organizer: 第89回 日本生化学会大会
  • Place of Presentation: 仙台市
  • Year and Date: 2016-09-25
• [Presentation] Molecular mechanism of etoposide induced 11q23 chromosome translocations. (2016)
  • Author(s): Jiying Sun
  • Organizer: 第89回 日本生化学会大会
  • Place of Presentation: 仙台市
  • Year and Date: 2016-09-25
• [Presentation] クロマチンの動的変化に着目したゲノム損傷応答の多様性の理解 (2016)
  • Author(s): 井倉 毅
  • Organizer: 日本環境変異原学会・変異機構研究会・第29回 夏の学校
  • Place of Presentation: 京都府京北町
  • Year and Date: 2016-09-10
  • Invited
• [Presentation] クロマチン制御から見たDNA 損傷応答研究の現状と今後の展望 (2016)
  • Author(s): 井倉 毅
  • Organizer: 東北大学加齢医学研究所セミナー
  • Place of Presentation: 仙台市
  • Year and Date: 2016-01-15
  • Invited
• [Presentation] ヒストン化学修飾から見たDNA修復研究の展望 (2015)
  • Author(s): 井倉 毅
  • Organizer: 第38回日本分子生物学会年会第88回日本生化学学会合同大会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] DNA損傷応答における動的クロマチン平衡とその意義 (2015)
  • Author(s): 井倉 毅
  • Organizer: 第38回日本分子生物学会年会第88回日本生化学会合同大会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-12-01
• [Presentation] DNAチェックポイント因子Rad9の分解を促進するCdk-Plk1依存的機構 (2015)
  • Author(s): 郡司未佳
  • Organizer: 第38回日本分子生物学会年会第88回日本生化学会合同大会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-12-01
• [Presentation] ピルビン酸キナーゼとピルビン酸デヒドロゲナーゼ複合体によるアセチルCoAの治産池消モデル (2015)
  • Author(s): 松田俊
  • Organizer: 第38回日本分子生物学会年会第88回日本生化学会合同大会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-12-01
• [Presentation] Involvement of a chromatin remodeling factor in chromosomal translocations (2015)
  • Author(s): 孫継英
  • Organizer: 第38回日本分子生物学会年会第88回日本生化学会合同大会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-12-01
• [Presentation] アセチル化を介した損傷クロマチンダイナミクス (2015)
  • Author(s): 井倉 毅
  • Organizer: 横浜市立大学生命医科学研究科セミナー
  • Place of Presentation: 横浜市
  • Year and Date: 2015-11-17
  • Invited
• [Presentation] Molecular mechanism of etoposide induced 11q23 chromosome translocation. Etoposideによる11q23 染色体転座形機構の解明 (2015)
  • Author(s): Jiying Sun
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-10-08
• [Presentation] The Role of Histone H2AX Dynamics in DNA Damage Response (2015)
  • Author(s): Tsuyoshi Ikura
  • Organizer: 第15回国際放射線研究会議（ICRR2015）
  • Place of Presentation: 京都市
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] Acetylation-dependent positive feedback loop regulation in dynamic chromatin equilibrium (2015)
  • Author(s): Tsuyoshi Ikura
  • Organizer: 大阪大学蛋白研セミナー、Institute for Protein Research (IPR) Seminar
  • Place of Presentation: 吹田市
  • Year and Date: 2015-05-18
  • Invited
• [Presentation] Chromatin dynamics in DNA damage response (2015)
  • Author(s): Tsuyoshi Ikura
  • Organizer: First DSV/CEA-RBC joint workshop
  • Place of Presentation: France
  • Year and Date: 2015-04-08
  • Int'l Joint Research / Invited