Mechanism of DNA damage responses mediated by acetylation of non-histone proteins

2012 Fiscal Year Final Research Report

• Project/Area Number: 23651050
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: National Institute of Radiological Sciences
• Principal Investigator: YASUDA Takeshi 独立行政法人放射線医学総合研究所, 緊急被ばく医療研究センター, 主任研究員 (60332269)
• Project Period (FY): 2011 – 2012
• Keywords: DNA損傷応答 / アセチル化 / DNA修復 / 相同組換え

Research Abstract

We have newly identified several non-histone target proteins involved in DNA damage response, which are acetylated by histone acetyltransferases such as CBP and p300 in vitro. Among the identified acetylated proteins, acetylation of human Rad52 protein was induced after DNA double-strand break (DSB). We identified the acetylation sites of Rad52 by mass spectrometry with the in vitro- acetylated purified Rad52 protein. Radiation-induced homologous recombination was inhibited by mutations at the acetylated sites. Our results indicates that acetylation of Rad52 is required for DSB repair by homologous recombination.

Research Products

• [Journal Article] Clinical Impact of Radiation-Resistant Mesenchymal Stem Cells in Bone Marrow Deduced from Preclinical Studies (2013)
  • Author(s): Michikawa, Y., Hazawa, M., Saotome-Nakamura, A., Yasuda, T., Gotoh, T., Tajima, K
  • Journal Title: Journal of Bone Marrow Researc Volume: 1
  • DOI: doi:10.4172/jbmr.1000101
  • Peer Reviewed
• [Journal Article] Sulfation of keratan sulfate proteoglycan reduces radiation-induced apoptosis in human Burkitt's lymphoma cell lines (2013)
  • Author(s): Nakayama, F., Umeda, S., Ichimiya, T., Kamiyama, S., Hazawa, M., Yasuda, T., Nishihara, S., Imai, T
  • Journal Title: FEBS Letters Volume: 587 Pages: 231-237
  • DOI: doi:10.1016/j.febslet.2012.12.002.
  • Peer Reviewed
• [Journal Article] Structural stability of human fibroblast growth factor-1 is essential for protective effects against radiation-induced intestinal damage (2013)
  • Author(s): Nakayama, F., Umeda, S., Yasuda, T., Asada, M., Motomura, K., Suzuki, M., Zakrzewska, M., Imamura, T., and Imai, T
  • Journal Title: Int. J. Radiat. Biol. Phys. Volume: 85 Pages: 477-483
  • DOI: doi:10.1016/j.ijrobp.2012.04.042
  • Peer Reviewed
• [Journal Article] Vitronectin improves cell survival after radiation injury in human umbilical vein endothelial cells (2012)
  • Author(s): Hazawa, M., Yasuda, T. (corresponding author), Noshiro, K., Saotome-Nakamura, A., Fukuzaki, T., Michikawa, Y., Gotoh, T., and Tajima, K.
  • Journal Title: FEBS Open Bio Volume: 2 Pages: 334-338
  • DOI: doi:org/10.1016/j.fob.2012.10.002
  • Peer Reviewed
• [Journal Article] The architecture of the CRL4^DDB2/CSA ubiquitin ligase, targeting and release of COP9 signalsome inhibition. (2011)
  • Author(s): Fischer, E., Scrima, A., Bohm, K., Matsumoto, S., Lingaraju, G.M., Faty, M., Yasuda, T., Cavadini, S., Wakasugi, M., Hanaoka, F., Iwai S., Gut, H., Sugasawa, K., Thoma, N.H.
  • Journal Title: Cell Volume: 147 Pages: 1024-1039
  • DOI: doi:10.1016/j.cell.2011.10.035
  • Peer Reviewed
• [Journal Article] Effects of Carbon Ion Beam on Putative Colon Cancer Stem Cells and Its Comparison with X-rays (2011)
  • Author(s): Cui, X., Oonishi, K., Tsujii, H., Yasuda, T., Matsumoto, Y., Furusawa, Y., Akashi, M., Kamada, T. and Okayasu, R
  • Journal Title: Cancer Research Volume: 71 Pages: 3676-3687
  • DOI: doi:10.1158/0008-5472.CAN-10-2926
  • Peer Reviewed
• [Journal Article] Fibroblast Growth Factor-12 (FGF12) Translocation into Intestinal Epithelial Cells Is Dependent on a Novel Cell-penetrating Peptide Domain (2011)
  • Author(s): Nakayama, F., Yasuda, T., Umeda, S., Asada, M., Imamura, T., Meineke, V., and Akashi, M
  • Journal Title: J. Biol. Chem. Volume: 286 Pages: 25823-25834
  • DOI: doi:10.1074/jbc.M110.198267
  • Peer Reviewed
• [Presentation] DNA修復におけるクロマチン構造の影響とヒストンアセチル化酵素の役割 (2013)
  • Author(s): 安田 武嗣
  • Organizer: 平成25年東京RBC新春放談会
  • Place of Presentation: 千葉(招待講演)
  • Year and Date: 2013-01-26
• [Presentation] DNA損傷によるヒトRad52タンパク質のアセチル化は、DNA二重鎖切断部位への集積に必要である (2012)
  • Author(s): 安田 武嗣、齋藤健吾、香川 亘、荻 朋男、鈴木健祐, 堂前 直, 日野拓也、中沢 由華、早乙女(中邑) 愛、加藤 宝光、Matthew Genet、羽澤 勝治、冨田 雅典、花岡 文雄、菅澤 薫、Penny Jeggo、岡安 隆一、田嶋 克史、胡桃坂 仁志
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡
  • Year and Date: 20121211-14
• [Presentation] ヒト間葉系幹細胞におけるヒトRad52タンパク質のDNA損傷によるアセチル化誘導 (2012)
  • Author(s): 早乙女 愛、安田 武嗣、齋藤 健吾、香川 亘、荻 朋男、鈴木 健祐、堂前 直、日野 拓也、中沢 由華、羽澤 勝治、花岡 文雄、菅澤 薫、岡安 隆一、胡桃坂 仁志、田嶋 克史
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡
  • Year and Date: 20121211-14
• [Presentation] Acetylation of human Rad52 protein by CBP/p300 (2012)
  • Author(s): Takeshi Yasuda, Kengo Saito, Wataru Kagawa, Tomoo Ogi, Takehiro Suzuki, Naoshi Dohmae, Takuya Hino, Yuka Nakazawa, Ai Saotome-Nakamura, Takamitsu Kato, Matthew Genet, Masaharu Hazawa, Masanori Tomita, Fumio Hanaoka, Kaoru Sugasawa, Penny Jeggo, Ryuichi Okayasu, Katsushi Tajima, Hitoshi Kurumizaka
  • Organizer: The 8th 3R symposium
  • Place of Presentation: 兵庫県
  • Year and Date: 20121125-28
• [Presentation] DNA damage-induced acetylation of human Rad52 protein in human mesenchymal stem cells (2012)
  • Author(s): Ai Saotome-Nakamura, Takeshi Yasuda, Kengo Saito, Wataru Kagawa, Tomoo Ogi, Takehiro Suzuki, Naoshi Dohmae, Takuya Hino, Yuka Nakazawa, Masaharu Hazawa, Fumio Hanaoka, Kaoru Sugasawa, Ryuichi Okayasu, Hitoshi Kurumizaka, Katsushi Tajima
  • Organizer: The 8th 3R symposium
  • Place of Presentation: 兵庫県
  • Year and Date: 20121125-28
• [Presentation] 非ヒストンタンパク質のアセチル化修飾を介したDNA修復制御機構 (2012)
  • Author(s): 安田 武嗣
  • Organizer: 遺伝研研究集会 「遺伝情報の安定性を支える分子メカニズム」
  • Place of Presentation: 三島
  • Year and Date: 20121003-04
• [Presentation] DNA損傷応答に関わる新規アセチル化標的タンパク質の同定 (2012)
  • Author(s): 安田 武嗣、齋藤 健吾、香川 亘、荻 朋男、鈴木 健祐、堂前 直、日野 拓也、中沢 由華、早乙女 愛、羽澤 勝治、花岡 文雄、菅澤 薫、岡安 隆一、胡桃坂 仁志、田嶋 克史
  • Organizer: 日本遺伝学会 第84回大会
  • Place of Presentation: 福岡
  • Year and Date: 20120924-26
• [Presentation] Reconstitution of mammalian nucleotide excision repair: molecular basis for DNA damage recognition (2011)
  • Author(s): Kaoru Sugasawa, Daisuke Tone, Takeshi Yasuda, Fumio Hanaoka
  • Organizer: 第34回 日本分子生物学会
  • Place of Presentation: パシフィコ横浜, 横浜市
  • Year and Date: 2011-12-17
• [Presentation] Functional analysis of the CRL4DDB2 E3 ligase in mammalian nucleotide excision repair (2011)
  • Author(s): Syota Matsumoto, Takeshi Yasuda, Naoshi Dohmae, Eric S. Fischer, Nicolas H. Thoma, Ryotaro Nishi, Fumio Hanaoka, Kaoru Sugasawa
  • Organizer: 第34回 日本分子生物学会
  • Place of Presentation: パシフィコ横浜, 横浜市
  • Year and Date: 2011-12-16
• [Presentation] Analysis of molecular mechanisms underlying regulation of Rad52 function by acetylation (2011)
  • Author(s): Takuya Hino, Kengo Saito, Takeshi Yasuda, Takehiro Suzuki, Naoshi Dohmae, Wataru Kagawa, Hitoshi Kurumizaka
  • Organizer: 第34回 日本分子生物学会
  • Place of Presentation: パシフィコ横浜, 横浜市
  • Year and Date: 2011-12-15
• [Presentation] FGF12の小腸に対する放射線防護効果について (2011)
  • Author(s): 中山 文明, 梅田 禎子, 安田 武嗣, 浅田 眞弘, 鈴木 理, 今村 亨, 今井 高志
  • Organizer: 日本放射線影響学会 第54回大会
  • Place of Presentation: 神戸商工会議所会館, 神戸
  • Year and Date: 2011-11-17
• [Presentation] 私の選択:研究者キャリアパスにおける岐路に立って (2011)
  • Author(s): 安田 武嗣
  • Organizer: 日本放射線影響学会 第54回大会
  • Place of Presentation: 神戸商工会議所会館, 神戸
  • Year and Date: 2011-11-17
• [Patent(Industrial Property Rights)] 細胞膜透過性の繊維芽細胞増殖因子の医療用途 (2012)
  • Inventor(s): 中山文明、梅田禎子、安田武嗣、藤田真由美、今井高志
  • Industrial Property Rights Holder: 同上
  • Industrial Property Number: 特願2012-259816
  • Filing Date: 2012-11-28