Dynamics of TIP60 complex in the network of DNA damage response signaling

2013 Fiscal Year Final Research Report

• Project/Area Number: 23510061
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation/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)
• Project Period (FY): 2011 – 2013
• Keywords: TIP60複合体 / ヒストンアセチル化 / ブロモドメイン蛋白質

Research Abstract

We and other group have shown that TIP60 histone acetyltransferase complex regulates hyperacetylation of histone H2AX and H4 at DNA damage sites, which is crucial for the higherorder chromatin alteration. However, it remains unclear how assembly of TIP60 is regulated at DNA damage sites. We have previosuly identified the bromodomain protein, BRDX, in the purified TIP60 complex. We found that the depletion of BRDX in cells impairs the assembly of TIP60 at DNA damage sites. This finding suggest that BRDX is required for the assembly of TIP60 at DNA damage sites. Moreover, we showed that the acetylation of histone H2AX by TIP60 is required for the retention of NBS1 at DNA damage sites. Since it has been reported that TIP60 functions as anti-cancer signaling molecule, we are now investigating whether chromatin reorganization via TIP60-BRDX complex is involved in the anti-cancer signaling pathway or not.

Research Products

• [Journal Article] Activation of the SUMO modification system is required for the accumulation of RAD51 at sites containing DNA damage (2013)
  • Author(s): Shima H, Suzuki H, Sun J, Kono K, Shi L, Kinomura A, Horikoshi Y, Ikura T, Ikura M, Kanaar R, Igarashi K, Saitoh H, Kurumizaka H, Tashiro S
  • Journal Title: J Cell Sci Volume: (Epub ahead of print)
• [Journal Article] Involvement of homologous recombination in the synergism between cisplatin and poly(ADP-ribose) polymerase inhibition (2013)
  • Author(s): Sakogawa K, Aoki Y, Misumi K, Hamai Y, Emi M, Hihara J, Shi L, Kono K, Horikoshi Y, Sun J, Ikura T, Okada M, Tashiro S
  • Journal Title: Cancer Sci Volume: (Epub ahead of print)
  • DOI: 10.1111/cas.12281
• [Journal Article] A novel interplay between the Fanconi anemia core complex and ATR-ATRIP kinase during DNA cross-link repair (2013)
  • Author(s): Tomida J, Itaya A, Shigechi T, Unno J, Uchida E, Ikura M, Masuda Y, Matsuda S, Adachi J, Kobayashi M, Meetei AR, Maehara Y, Yamamoto KI, Kamiya K, Matsuura A, Matsuda T, Ikura T, Ishiai M, Takata M
  • Journal Title: Nucleic Acids Res Volume: (Epub ahead of print)
• [Journal Article] Involvement of ribonucleotide reductase-M1 in 5-fluorouracil-induced DNA damage in esophageal cancer cell lines (2013)
  • Author(s): Aoki, Y., Sakogawa, K., Hihara, J., Emi, M., Hamai,Y., Kono, K., Shi, L., Sun, J., Kitao, H., Ikura, T., Niida, H., Nakanishi, M., Okada, M., Tashiro, S
  • Journal Title: Int J Oncol Volume: 42 Pages: 1951-1960
• [Journal Article] Heterocomplex Formation by Arp4 and ƒÀ-Actin Involved in Integrity of the Brg1 Chromatin Remodeling Complex (2012)
  • Author(s): Nishimoto, N., Watanabe, M., Watanabe, S., Sugimoto, N., Yugawa,T., Ikura, T., Koiwai, O., Kiyono,T and Fujita, M
  • Journal Title: J. Cell Sci Volume: 125 Pages: 3870-3882
• [Journal Article] Bach1-mediated suppression of p53 is inhibited by p19(ARF) independently of MDM2 (2012)
  • Author(s): Nishizawa, H., Ota, K., Dohi, Y., Ikura, T., Igarashi, K
  • Journal Title: Cancer Sci Volume: 103 Pages: 897-903
• [Journal Article] A new system for analyzing ionizing radiation-induced chromosome abnormalities (2012)
  • Author(s): Shi L., Fujioka K., Sun J., Kinomura A., Inaba T., Ikura T., Ohtaki M., Yoshida M., Kodama Y., Livingston G.K., Kamiya K., Tashiro S
  • Journal Title: Radiat. Res Volume: 117 Pages: 533-538
• [Journal Article] Purification of the human SMN-GEMIN2 complex and assessment of its stimulation of RAD51-mediated DNA recombination reactions (2011)
  • Author(s): Takaku, M., Tsujita, T., Horikoshi, N., Takizawa, Y., Qing, Y., Hirota, K., Ikura, M., Ikura, T., Takeda, S., Kurumizaka, H
  • Journal Title: Biochemistry Volume: 50 Pages: 6797-6805
• [Journal Article] Methionine Adenosyltransferase II Serves As a Transcriptional Corepressor of Maf Oncoprotein (2011)
  • Author(s): Katoh, Y, Ikura, T., Hoshikawa,Y., Tashiro, S., Ohta, M., Kera, Y., Noda, T., and Igarashi, K
  • Journal Title: Mol Cell Volume: 41 Pages: 554-566
• [Presentation] DNA 損傷応答におけるヒストンH2AX のダイナミクス (2013)
  • Author(s): 井倉 毅
  • Organizer: 第1回ヒストンヴァリアント研究会
  • Place of Presentation: 九州大学医学部, 福岡市
  • Year and Date: 2013-03-08
• [Presentation] クロマチンの動的変化を介したDNA 損傷応答シグナルのエピジェネティクス制御機構 (2013)
  • Author(s): 井倉 毅
  • Organizer: 文部科学省第五回生物学・化学・情報科学融合のための戦略的先進理工学研究基盤の形成支援事業シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2013-03-06
• [Presentation] クロマチンの動的変化を介したDNA 損傷応答シグナルのエピジェネティクス制御 (2012)
  • Author(s): 井倉 毅
  • Organizer: 第3次対がん10 か年総合戦略 平成16年-25年度・文部科学省がん支援活動、合同公開シンポジウム
  • Place of Presentation: 日学術総合センター、一橋記念講堂、東京都
  • Year and Date: 20120130-31
• [Presentation] DNA 損傷応答シグナル活性化におけるクロマチンの動的変化とプロテアソーム蛋白質分解系とのクロストーク (2012)
  • Author(s): 井倉 毅
  • Organizer: 第80回NM-GCOE セミナー
  • Place of Presentation: 東北大学医学部, 仙台市
  • Year and Date: 2012-08-24
• [Presentation] クロマチンの動的変化を介したDNA 損傷応答シグナルのエピジェネティクス制御 (2012)
  • Author(s): 井倉 毅
  • Organizer: 第10回口腔医科学フロンティア
  • Place of Presentation: 大阪大学歯学部記念館、吹田市
  • Year and Date: 2012-03-03
• [Presentation] The role of histone H2AX eviction in DNA damage-induced checkpoint activation (2011)
  • Author(s): 井倉正枝, 松浦嘉奈子, 田代 聡, 島 弘季, 松田 涼, 五十嵐和彦, 井倉 毅
  • Organizer: 第34回日本分子生物学会年会 ワークショップ
  • Place of Presentation: 横浜市
  • Year and Date: 2011-12-15
• [Presentation] ゲノム損傷におけるクロマチンの動的変化とエピジェネティクス制御 (2011)
  • Author(s): 井倉 毅
  • Organizer: 第3回エピジェネティクス療法研究会
  • Place of Presentation: 東京都
  • Year and Date: 2011-11-03
• [Presentation] DNA 損傷応答シグナルにおけるTIP60 ヒストンアセチル化酵素複合体のダイナミクス (2011)
  • Author(s): 井倉 毅
  • Organizer: 構造エピゲノム研究会 第4回ワークショップ
  • Place of Presentation: 横浜市
  • Year and Date: 2011-07-27
• [Presentation] ゲノム疾患研究の現状と未来 (2011)
  • Author(s): 井倉 毅
  • Organizer: 神戸大学バイオシグナル研究センター
  • Place of Presentation: 神戸市
  • Year and Date: 2011-06-10
• [Book] 遺伝情報の発現制御 -転写機構からエピジェネティクスまで- (2012)
  • Author(s): David S. Latchman (第3章翻訳、松田 俊、井倉正枝、井倉毅)
  • Total Pages: 429
  • Publisher: メディカル・サイエンス・インターナショナル
• [Remarks] ホームページ
  • URL: http://house.rbc.kyoto-u.ac.jp/mutagenesis2/