Isolation of repair-deficient mutants for clustered DNA damage

• Project/Area Number: 19510062
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Japan Atomic Energy Agency
• Principal Investigator: SHIKAZONO Naoya Japan Atomic Energy Agency, 先端基礎研究センター, 研究主幹 (10354961)
• Co-Investigator(Kenkyū-buntansha): YOKOYA Akinari 独立行政法人日本原子力研究開発機構, 研究主幹 (10354987)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 放射線生物影響 / クラスターDNA損傷 / 突然変異 / DNA修復欠損株 / 大腸菌 / 修復合成 / 電離放射線 / LET / 突然変異株 / DNA修復

Research Abstract

We have found that the position and types of lesions within the clustered DNA damage are strongly relevant to the biological consequences of clustered DNA damage. We have also demonstrated that the clustering of DNA damage is strongly related to the ionizing density of the radiation. These results have important implications for both the understanding of underlying mechanisms of radiation action to cells and the practical application of ionizing radiation (ie.assessment of low dose risk, improvement of radiation therapy etc.).

Research Products

• [Journal Article] The yield, processing, and biological consequences of clustered DNA damage induced by ionizing radiation. (2009)
  • Author(s): Shikazono, N., Noguchi, M., Fujii, K., Urushibara, A., Yokoya, A.
  • Journal Title: J Radiat Res. 50 Pages: 27-36
  • NAID: 110007042080
  • Peer Reviewed
• [Journal Article] Processing of thymine glycol in a clustered DNA damage site: mutagenic or cytotoxic. (2009)
  • Author(s): Bellon, S., Shikazono, N., Cunniffe, S., Lomax, M., O'Neill, P.
  • Journal Title: Nucleic Acids Res. 37 Pages: 4430-4440
  • Peer Reviewed
• [Journal Article] Biological consequences of potential repair intermediates of clustered base damage site in Escherichia coli. (2009)
  • Author(s): Shikazono, N., O'Neill, P.
  • Journal Title: Mutat Res. 669 Pages: 162-168
  • Peer Reviewed
• [Journal Article] Processing of thymine glycol in a clustered DNA damage site : mutagenic or cytotoxic. (2009)
  • Author(s): Bellon, S., Shikazono, N., Cunniffe, S., Lomax, M., O'Neill, P.
  • Journal Title: Nucleic Acids Res. 37 Pages: 4430-4440
  • Peer Reviewed
• [Journal Article] The Yield, Processing, and Biological Consequences of Clustered DNA Damage Induced by Ionizing Radiation (2009)
  • Author(s): N. Shikazono, M. Noguchi, K. Fujii, A. Urushibara, A. Yokoya
  • Journal Title: Journal of Radiation Research 50 Pages: 27-36
  • NAID: 110007042080
  • Peer Reviewed
• [Journal Article] LET dependence of the yield of single-, double-strand breaks and base lesions in fully hydrated plasmid DNA films by 4He(2+) ion irradiation. (2008)
  • Author(s): Urushibara, A., Shikazono, N., O'Neill, P., Fujii, K., Wada, S., Yokoya, A.
  • Journal Title: Int J Radiat Biol. 84 Pages: 23-33
  • Peer Reviewed
• [Journal Article] Induction of Single Strand Breaks, and Base Lesions in Plasmid DNA Films induced by Carbon, Nitrogen, and Oxygen KLL Auger Process (2008)
  • Author(s): K. Fujii, A. Yokoya, N. Shikazono
  • Journal Title: International Journal of Radiation Biology 50 Pages: 1104-1111
  • Peer Reviewed
• [Journal Article] Studies of Soft X-ray-induced Auger Effect on the Induction of DNA Damage (2008)
  • Author(s): A. Yokoya, K. Fujii, N. Shikazono, K. Akamatsu, A. Urushibara, R. Watanabe
  • Journal Title: International Journal of Radiation Biology 50 Pages: 1069-1081
  • Peer Reviewed
• [Journal Article] DNA Damage induced by the Direct Effect of Radiation (2008)
  • Author(s): A. Yokoya, N. Shikazono, K. Fujii, A. Urushibara, K. Akamatsu, R. Watanabe
  • Journal Title: Radiation Physics and Chemistry 77 Pages: 1280-1285
  • Peer Reviewed
• [Journal Article] LET dependence of the yield of single-,double strand breaks and base lesions in fully hydrated plasmid DNA films by 4He^<2+>ion irradiation (2008)
  • Author(s): A. Urushibara, N. Shikazono, P. O'Neill, K. Fujii, S. Wada, A. Yokoya
  • Journal Title: International Journal of Radiation Biology 84 Pages: 23-33
  • Peer Reviewed
• [Journal Article] DNA Damage induced by direct effect of radiation (2008)
  • Author(s): A.Yokoya, N. Shikazono, K. Fujii, A. Urushibara, K. Akamatsu, R. Watanabe
  • Journal Title: Radiation Physics and Chemistry (in press)
  • Peer Reviewed
• [Presentation] 大腸菌におけるクラスターDNA損傷誘発突然変異 (2009)
  • Author(s): 鹿園直哉、野口実穂、漆原あゆみ、Peter O' Neill、横谷明徳
  • Organizer: 第52回日本放射線影響学会
  • Place of Presentation: 北九州
  • Year and Date: 2009-11-12
• [Presentation] イオンビーム照射により高水和DNAフィルム中に誘発されるDNA鎖切断及び塩基損傷収率のLET依存性 (2009)
  • Author(s): 横谷明徳、牛込剛史、田内広、鈴木雅雄、鶴岡千鶴、野口実穂、藤井健太郎、鹿園直哉、渡邊立子
  • Organizer: 第52回日本放射線影響学会
• [Presentation] 大腸菌におけるクラスターDNA損傷誘発突然変異 (2009)
  • Author(s): 鹿園直哉、野口実穂、漆原あゆみ、Peter O'Neill、横谷明徳
  • Organizer: 第52回日本放射線影響学会
• [Presentation] 同一鎖上に配置されたクラスターDNA損傷のプロセシングについて (2009)
  • Author(s): 野口実穂、漆原あゆみ、横谷明徳、鹿園直哉
  • Organizer: 第52回日本放射線影響学会
• [Presentation] Processing and biological consequences of clustered DNA damage containing a single strand break and an AP site. (2009)
  • Author(s): Shikazono, N., Noguchi, M., Urushibara, A., O'Neill, P., Yokoya, A.
  • Organizer: 第32回日本分子生物学会
• [Presentation] 8-oxoGを含むクラスターDNA損傷誘発突然変異における一本鎖切断の影響 (2008)
  • Author(s): 野口実穂, 漆原あゆみ, 横谷明徳, 鹿園直哉
  • Organizer: 日本放射線影響学会第51回大会
  • Place of Presentation: 北九州市
  • Year and Date: 2008-11-21
• [Presentation] 鎖切断と脱塩基部位からなるクラスターDNA損傷の生物効果 (2008)
  • Author(s): 鹿園直哉, 野口実穂, 漆原あゆみ, P. O'Neill, 横谷明徳
  • Organizer: 日本放射線影響学会第51回大会
  • Place of Presentation: 北九州市
  • Year and Date: 2008-11-20
• [Presentation] プラスミドDNAに対する高LET放射線による非DSB性多重SSB誘発の可能性 (2008)
  • Author(s): 横谷明徳, 鹿園直哉, 藤井健太郎
  • Organizer: 日本放射線影響学会第51回大会
  • Place of Presentation: 北九州市
  • Year and Date: 2008-11-20
• [Presentation] X線誘発損傷に対するシリビンとその類似体の in vitro でのDNA防護効果 (2008)
  • Author(s): 付海英, 林銘章, 端邦樹, 室屋裕佐, 藤井健太郎, 勝村庸介, 横谷明徳, 鹿園直哉, 籏野嘉彦
  • Organizer: 日本放射線影響学会第51回大会
  • Place of Presentation: 北九州市
  • Year and Date: 2008-11-19
• [Presentation] 軟X線照射によって乾燥プラスミドDNAに生じる分子損傷の収率 (2008)
  • Author(s): 藤井健太郎, 横谷明徳, 鹿園直哉
  • Organizer: 第51回放射線化学討論会
  • Place of Presentation: つくば市
  • Year and Date: 2008-10-16
• [Presentation] 軟X線によってDNA分子内に生じるサイト選択的分子変化 (2008)
  • Author(s): 藤井健太郎, 横谷明徳, 鹿園直哉
  • Organizer: 分子科学討論会
  • Place of Presentation: 福岡市
  • Year and Date: 2008-09-25
• [Presentation] Lethality and Mutagenesis of E. coli Cells Irradiated with Soft X-rays (2008)
  • Author(s): T. Suzaka, N. Shikazono, K. Fujii, A. Yokoya, H. Tauchi
  • Organizer: 2nd Asia-Pasific Symposium on Radiation Chemistry
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2008-08-30
• [Presentation] A Qualitative Analysis on the Yield of Radiation-induced DNA Strand Breaks in Hydrated Plasmids (2008)
  • Author(s): N. Shikazono, A. Urushibara, K. Fujii, A. Yokoya
  • Organizer: 2nd Asia-Pasific Symposium on Radiation Chemistry
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2008-08-29
• [Presentation] Mutagenic potential of 8-oxo-7,8-dihydroguanine depends on the location of a single strand break within a cluster (2008)
  • Author(s): M. Noguchi, A. Urushibara, A. Yokoya, P. O'Neill, N. Shikazono
  • Organizer: 10^<th> International Workshop Radiation Damage to DNA
  • Place of Presentation: Urabandai, Japan
  • Year and Date: 2008-06-10
• [Presentation] Processing of clustered DNA damage site in Escherichia coli. (2008)
  • Author(s): N. Shikazono, C. Pearson, J. Thacker, P. O'Neill
  • Organizer: 10^<th> International Workshop Radiation Damage to DNA
  • Place of Presentation: Urabandai, Japan
  • Year and Date: 2008-06-09
• [Presentation] DNA Damage Specrtra in Ultrasoft X-ray Region : Effect of Inner-shell Ionization of Carbon, Nitrogen and Oxygen Atoms on the Damage Induction (2008)
  • Author(s): K. Fujii, A. Yokoya, N. Shikazono
  • Organizer: 10^<th> International Workshop Radiation Damage to DNA
  • Place of Presentation: Urabandai, Japan
  • Year and Date: 2008-06-09
• [Presentation] A Novel Technique using DNA Denaturation to Detect Prompt and Enzymatically Induced Single Strand Breaks Produced in a Clustered Damage Site (2008)
  • Author(s): A. Yokoya, N. Shikazono, A. Urushibara, K. Fujii
  • Organizer: 10^<th> International Workshop Radiation Damage to DNA
  • Place of Presentation: Urabandai, Japan
  • Year and Date: 2008-06-09
• [Presentation] 鎖切断と脱塩基部位からなるクラスターDNA損傷の生物効果 (2008)
  • Author(s): 鹿園直哉、野口実穂、漆原あゆみ、Peter O'Neill、横谷明徳
  • Organizer: 第51回日本放射線影響学会
• [Presentation] 8-oxoGを含むクラスターDNA損傷誘発突然変異における1本鎖切断の影響 (2008)
  • Author(s): 野口実穂、漆原あゆみ、横谷明徳、鹿園直哉
  • Organizer: 第51回日本放射線影響学会
• [Presentation] Mutagenic potential of clustered DNA damage site in Escherichia coli. (2008)
  • Author(s): Shikazono, N., Pearson, C., Thacker, J., O'Neill, P.
  • Organizer: The 9th International Workshop on Radiation Damage to DNA
• [Presentation] DNA damages induced by ion particles and photons with various energies. (2008)
  • Author(s): Yokoya, A.
  • Organizer: The 9th International Workshop on Radiation Damage to DNA
• [Presentation] 8-oxoGとDHTからなるクラスターDNA損傷のプロセシング経路 (2007)
  • Author(s): 鹿園直哉、Colin Pearson、John Thacker、Peter O'Neill
  • Organizer: 第50回日本放射線影響学会
• [Presentation] Mutagenic potential of clustered DNA damage site in Escherichia coli. (2007)
  • Author(s): Shikazono, N., Pearson, C., Thacker, J., O'Neill, P.
  • Organizer: The 13th International Congress of Radiation Research
• [Presentation] Mutagenic potential of clustered DNA damage site in Escherichia coli (2007)
  • Author(s): N. Shikazono, C. Pearson, J. Thacker. P. O'Neill
  • Organizer: 13th International Congress on Radiation Researc
  • Place of Presentation: San Fransisco,USA
• [Presentation] Induction of strand breaks,base lesions,and clustered damage in dry plasmid DNA films induced by carbon,nitrogen and oxygen KLL Auger process (2007)
  • Author(s): K. Fujii, A. Yokoya, N. Shikazon
  • Organizer: 6th Auger Symposium:An International Symposium on Physical, Molecular, Cellular, and Medical Aspects of Auger Processes
  • Place of Presentation: Boston,USA
• [Presentation] Induction of strand breaks and base lesions in dry plasmid DNA films unduced by 270-560eV ultrasoft X-rays (2007)
  • Author(s): K. Fujii, A. Yokoya, N. Shikazono
  • Organizer: 13th Intemational Congress of Radiation Research
  • Place of Presentation: San Fransisco,USA
• [Presentation] Anovel technique using DNA denaturation to analyze clustered DNA damage sitesinduced by densely ionizing radiation (2007)
  • Author(s): A. Yokoya, N. Shikazono, T. Ushisome, A. Urushibara, K. Fujii
  • Organizer: 13th International Congress of Radiation Research
  • Place of Presentation: San Fransisco,USA
• [Presentation] Biological consequences of bistanded clustered DNA damage in Escherichia coli (2007)
  • Author(s): N. Shikazono, C. Pearson, J. Thacker, P. O'Neill
  • Organizer: The 7th International Symposium on Advanced Sdence Research, Charged Particle and Photon Interaction with Matter
  • Place of Presentation: 東海村(日本原子力研究開発機構),茨城県
• [Presentation] Mutagenic potential of non-DSB clustered damage containing 8-oxoG and single strand break (2007)
  • Author(s): M. Noguchi, A. Urushibara, A Yokoya, N. Shikazono
  • Organizer: The 7th International Symposium on Advanced Science Research;Charged Particle and Photon Interaction with Matter
  • Place of Presentation: 東海村(日本原子力研究開発機構),茨城県
• [Presentation] Strand breaks and base lesions in dry plasmid DNA films induced by monochromaticultrasoft X-rays (2007)
  • Author(s): K. Fujii, A. Yokoya, N. Shikazono
  • Organizer: The 7th International Symposium on Advanced Science Research;Charged Particle and Photon Interaction with Matter
  • Place of Presentation: 東海村(日本原子力研究開発機構),茨城県
• [Presentation] 8-oxoGとDHTからなるクラスターDNA損傷のプロセシング経路 (2007)
  • Author(s): 鹿園 直哉, C. Pearson, J. Thacker, P. O'Neill
  • Organizer: 日本放射線影響学会第50回大会
  • Place of Presentation: 千葉市(幕張メッセ),千葉県
• [Presentation] 非2本鎖切断型クラスター損傷(8-oxoGと鎖切断)の突然変異誘発 (2007)
  • Author(s): 野口 実穂、漆原 あゆみ、横谷 明徳、鹿園 直哉
  • Organizer: 日本放射線影響学会第50回大会
  • Place of Presentation: 千葉市(蒜張メッセ),千葉県
• [Presentation] 放射線によりプラスミドDNAの両鎖に生じた非DSB性多重SSBのDNAの変性を利用した新しい定量法 (2007)
  • Author(s): 横谷 明徳、漆原 あゆみ、藤井 健太郎、鹿園 直哉
  • Organizer: 日本放射線影響学会第50回大会
  • Place of Presentation: 千葉布(幕張メッセ),千葉県
• [Presentation] 放射光単色軟X線によりDNA中に生じる主鎖切断収量及び修復酵素をプローブとして用いた塩基損傷の定量 (2007)
  • Author(s): 藤井 健太郎、横谷 明徳、鹿園 直哉
  • Organizer: 日本放射線化学討論会第50回大会
  • Place of Presentation: 京都大学(宇治キャンパス),京都府
• [Remarks]
  • URL: http://asrc.jaea.go.jp/asr_ja/co_p/groups/g_8_j.html
• [Remarks] クラスターDNA損傷による生物効果-近接したDNA損傷による突然変異誘発-未来を拓く原子力原子力機構の研究開発成果2008、6-5.
  • URL: http://jolisfukyu.tokai-sc.jaea.go.jp/fukyu/mirai/2008/index_set.html
• [Remarks] クラスターDNA損傷の生物影響日本原子力研究開発機構基礎科学ノートVol16, 2009, 14-17.
  • URL: http://asrc.jaea.go.jp/asr_ja/co_p/online_note.html
• [Remarks]
  • URL: http://asrc.jaea.go.jp/asr_ja/co_p/online_note.html