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2011 Fiscal Year Final Research Report

Strategy for the prediction and control of radiosensitivity based on the life-cycle and homeostasis of the DNA repair system

Research Project

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Project/Area Number 21689033
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Radiation science
Research InstitutionTokyo Institute of Technology

Principal Investigator

MATSUMOTO Yoshihisa  東京工業大学, 原子炉工学研究所, 准教授 (20302672)

Project Period (FY) 2009 – 2011
Keywords放射線治療生物学
Research Abstract

This study aimed to find a new approach to the prediction and control of radiosensitivity through the analyses of the life cycle-how proteins are generated and degraded - and homeostasis-how proteins are protected and recovered from dysfunctional status, such as denaturation - of proteins involved in DNA double-strand break repair through non-homologous end joining.We obtained the following major outcomes. First, we found regions in DNA ligase IV for chromatin binding and stabilization. Second, we found a protein required for the chromatin binding of XRCC4 and also clarified binding region in XRCC4. Third, we created a series of mutants of XRCC4 and XLF. In XRCC4, we found several mutants, other than potential phosphorylation site mutants, with elevated radiosensitivity, suggesting possible involvement of posttranslational modifications other than phosphorylation or protein-protein interaction. These results might show a new strategy for radiosensitization by targeting the protein-protein or protein-chromatin interactions.

  • Research Products

    (33 results)

All 2012 2011 2010 2009

All Journal Article (10 results) (of which Peer Reviewed: 7 results) Presentation (20 results) Book (3 results)

  • [Journal Article] DNA-PK inhibition causes a low level of H2AX phosphorylation and homologous recombination repair in Medaka (Oryzias latipes) cells. Biochem.2012

    • Author(s)
      Urushihara, Y., Kobayashi, J., Matsumoto, Y., Komatsu, K, Oda, S., Mitani, H.
    • Journal Title

      Biophys.Res.Commun.

      Volume: 429 Pages: 131-136

    • DOI

      DOI:10.1016/j.bbrc.2012.10.128.

    • Peer Reviewed
  • [Journal Article] Identification of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a novel target of Bisphenol A.2012

    • Author(s)
      Ito, Y., Ito, T., Karasawa, S., Enomoto, T., Nashimoto, A., Hase, Y., Sakamoto, S., Ito, T., Mimori, T., Matsumoto, Y., Yamaguchi, Y., Handa, H.
    • Journal Title

      PLos ONE

      Volume: 7(12) Pages: e50481

    • DOI

      DOI:10.1371/journal.pone.0050481.

    • Peer Reviewed
  • [Journal Article] Analysis ofKu and XRCC4 expressions of hypopharyngeal cancer tissues and results treated with chemoradiotherapy.2012

    • Author(s)
      Hayashi, J., Sakata, K., Someya, M., Matsumoto, Y., Satoh, M., Kataya, K., Hori, M., Takagi, M. and Hareyama, M.
    • Journal Title

      Oncol. Lett.

      Volume: 4 Pages: 151-155

    • DOI

      DOI:10.3892/ol.2012.674.

    • Peer Reviewed
  • [Journal Article] Gene expression associated with DNA-dependent protein kinase activity under normoxia, hypoxia and reoxygenation.2011

    • Author(s)
      Tsuchimoto,T., Sakata,K., Someya,M., Yamamoto,H., Hirayama,R., Matsumoto,Y., Furusawa,Y. and Hareyama,M.
    • Journal Title

      J.Radiat.Res

      Volume: 52 Pages: 464-471

    • DOI

      DOI:10.1269/jrr.10137.

    • Peer Reviewed
  • [Journal Article] The association of DNA-dependent protein kinase activity of peripheral blood lymphocytes with prognosis of cancer2011

    • Author(s)
      Someya,M., Sakata,K., Matsumoto,Y., Kamdar,R.P., Kai,M., Toyota,M. and Hareyama,M.
    • Journal Title

      Brit.J.Cancer

      Volume: 104 Pages: 1724-1729

    • DOI

      DOI:10.1038/bjc.2011.158.

    • Peer Reviewed
  • [Journal Article] DNA二重鎖切断に対する生体防御機構と医療応用2011

    • Author(s)
      松本義久
    • Journal Title

      表面科学

      Volume: 32(9) Pages: 569-574

    • Peer Reviewed
  • [Journal Article] DNA二重鎖切断の修復とシグナル伝達2011

    • Author(s)
      松本義久
    • Journal Title

      細胞TheCELL

      Volume: 43(6) Pages: 4-8

  • [Journal Article] Radiation-induced XRCC4 Association with Chromatin DNA Analyzed by Biochemical Fractionation2010

    • Author(s)
      Kamdar,R.P.and Matsumoto,Y.
    • Journal Title

      J.Radiat.Res

      Volume: 51 Pages: 303-313

    • Peer Reviewed
  • [Journal Article] 非相同末端結合の素過程の解明と臨床応用への展望2010

    • Author(s)
      松本義久、MukeshKumarSharma、RadhikaPankajKamdar
    • Journal Title

      癌の臨床

      Volume: 56 Pages: 431-435

  • [Journal Article] DNA切断の「認識」の分子生物学-The End is the Beginning2010

    • Author(s)
      松本義久
    • Journal Title

      電気学会

      Volume: OQD-10-002

  • [Presentation] Role of BRCT domains of DNA Ligase IV in its chromatin binding and recruitment of XRCC4.2012

    • Author(s)
      Liu, S., Kamdar, R.P., Adachi, N., Matsumoto, Y.
    • Organizer
      28th RBC-NIRS International Symposium, Kyoto (Coop-Inn Kyoto)
    • Place of Presentation
      Poster Presentation
    • Year and Date
      20121129-30
  • [Presentation] Regulation of non-homologous end joining repair mechanismof DNA double-strand break by kinase activity of DNA-PK.2012

    • Author(s)
      Sharma, M.K., Matsumoto, Y.
    • Organizer
      28th RBC-NIRS International Symposium, Kyoto (Coop-Inn Kyoto)
    • Place of Presentation
      Poster Presentation with Proffered Short Talk
    • Year and Date
      20121129-30
  • [Presentation] 生化学的分画法による XRCC4-DNAリガーゼIV複合体のクロマチン結合の解析(Chromatin binding of XRCC4-DNA ligase IV complex revealed bybiochemical fractionation analysis)2012

    • Author(s)
      Sicheng LIU, Radhika Pankaj KAMDAR, 足 立 典隆, 松本 義久
    • Organizer
      日本放射 線影響学会第55回大会
    • Place of Presentation
      東北大学(仙台)
    • Year and Date
      20120906-08
  • [Presentation] DNA二重鎖切断修復機構のアナトミーと医療応用への展望2012

    • Author(s)
      松本義久.
    • Organizer
      第5回QuantumMedicine研究会(茨城大学理学部公開シンポジウム/茨城大学研究推進プロジェクト「がん放射線治療に関する生命基礎研究」講演会)
    • Place of Presentation
      茨城大学理学部(水戸)
    • Year and Date
      2012-03-04
  • [Presentation] DNA-PK phosphorylation in XRCC4 and XLF and its role in DNA double-strand break repair through non-homologous end joining2011

    • Author(s)
      Sharma, M.K., Fukuchi, M., Imamichi, S., Matsumoto, Y.
    • Organizer
      14th International Congress of Radiation Research
    • Place of Presentation
      Walsaw, Poland
    • Year and Date
      20110828-0901
  • [Presentation] Assembly of non-homologous end joining machinery revealed by biochemical fractionation analysis2011

    • Author(s)
      Liu, S., Kamdar, R.P., Matsumoto, Y.
    • Organizer
      第17回国際癌治療増感研究会
    • Place of Presentation
      仙台(赤門鍼灸柔整専門学校)
    • Year and Date
      2011-06-24
  • [Presentation] DNA二重鎖切断修復におけるXRCC4の制御機構.2010

    • Author(s)
      福地命、Sharma,M.K.、Kamdar,R.P.、松本義久.
    • Organizer
      日本放射線影響学会第53回大会
    • Place of Presentation
      京都(京都テルサ)
    • Year and Date
      20101020-22
  • [Presentation] DNA-PK phosphorylation mediated regulation of NHEJ repair process of DNA double strand break2010

    • Author(s)
      Sharma, M.K., Matsumoto, Y.
    • Organizer
      日本放射線影響学会第53回大会
    • Place of Presentation
      京都(京都テルサ)
    • Year and Date
      20101020-22
  • [Presentation] Recruitment and assembly of XRCC4-DNA ligase IV complex on radiation damaged chromatin in situ revealed by biochemical fractionation analysis2010

    • Author(s)
      Kamdar, R.P., Liu, S., Matsumoto, Y.
    • Organizer
      日本放射線影響学会第53回大会
    • Place of Presentation
      京都(京都テルサ)
    • Year and Date
      20101020-22
  • [Presentation] DNA二重鎖切断修復におけるXRCC4の解析2010

    • Author(s)
      松本義久.
    • Organizer
      日本放射線影響学会第53回大会
    • Place of Presentation
      京都(京都テルサ)
    • Year and Date
      20101020-22
  • [Presentation] Identification of DNA-PK phosphorylation targets in XRCC4& XLF proteins and their physiological significance in the process of DNA double-strand break repair.2010

    • Author(s)
      Sharma, M.K., Matsumoto, Y.
    • Organizer
      56th Annual Meeting Radiation Research Society, Maui (Grand Wailea Resort Hotel and Spa)
    • Place of Presentation
      Hawaii,USA
    • Year and Date
      20100925-29
  • [Presentation] XRCC4: a bona fide substrate of DNA-PK in DNA double-strand break repair2010

    • Author(s)
      Matsumoto, Y.
    • Organizer
      56th Annual Meeting Radiation Research Society, Maui (Grand Wailea Resort Hotel and Spa)
    • Place of Presentation
      Hawaii,USA
    • Year and Date
      20100925-29
  • [Presentation] Assembly of non-homologous end-joining machinery on radiation-induced DNA double-strand breaks.2010

    • Author(s)
      Kamdar, R.P., Matsumoto, Y.
    • Organizer
      Ataxia- Telangiectasia Workshop 2010
    • Place of Presentation
      Redondo Beach (Crowne Plaza Hotel), CA,USA
    • Year and Date
      20100411-14
  • [Presentation] DNA-PK phosphorylation targets in XRCC4 and XLF proteins in DNA double-strand break repair2010

    • Author(s)
      Sharma, M.K., Matsumoto, Y.
    • Organizer
      Ataxia- Telangiectasia Workshop 2010
    • Place of Presentation
      Redondo Beach (Crowne Plaza Hotel), CA,USA
    • Year and Date
      20100411-14
  • [Presentation] 非相同末端結合の素過程の解明と臨床応用への展望2010

    • Author(s)
      松本義久、Sharma,M.K.、Kamdar,R.P.
    • Organizer
      第40回放射線による制癌シンポジウム
    • Place of Presentation
      札幌(さっぽろ芸文館)
    • Year and Date
      2010-07-10
  • [Presentation] DNA-PK Phosphorylation Sites Essential for DNA Double-Strand Break Repair And Its Possible Application in Cancer Therapy2010

    • Author(s)
      Sharma, M.K., Matsumoto, Y.
    • Organizer
      第16回国際癌治療増感研究会
    • Place of Presentation
      岐阜(県民文化ホール未来会館)
    • Year and Date
      2010-06-19
  • [Presentation] The true substrate of DNA-dependent protein kinase (DNA-PK) and the significance of phosphorylation2010

    • Author(s)
      Sharma, M.K., Matsumoto, Y.
    • Organizer
      第12回癌治療増感研究シンポジウム ,第9回国際癌治療増感研究協会国際研究奨励賞受賞記念講演(AL)
    • Place of Presentation
      奈良(猿沢荘)
    • Year and Date
      2010-02-13
  • [Presentation] 生細胞内でのDNA-PKにょるXRCC4のリン酸化:ヒト、マウス細胞間での相違.2009

    • Author(s)
      福地命,Sharma,M.K.,松本義久.
    • Organizer
      日本放射線影響学会第52回大会
    • Place of Presentation
      広島(広島市南区民文化センター)
    • Year and Date
      20091111-13
  • [Presentation] DNA二重鎖切断の修復におけるXRCC4およびXLFのDNA-PKによる新たなリン酸化部位2009

    • Author(s)
      Sharma,M.K.,Matsumoto,Y.
    • Organizer
      日本放射線影響学会第52回大会
    • Place of Presentation
      広島(広島市南区民文化センター)
    • Year and Date
      20091111-13
  • [Presentation] Assembly of XRCC4-DNA ligase IV-XLF complex on radiation damaged chromatin in situ revealed by biochemical fractionation analysis2009

    • Author(s)
      Kamdar, R.P., Matsumoto, Y.
    • Organizer
      日本放射線影響学会第52回大会
    • Place of Presentation
      広島(広島市南 区民文化センター)
    • Year and Date
      20091111-13
  • [Book] DNARepair-New Research Directions2012

    • Author(s)
      Matsumoto, Y. Imamichi, S., Fukuchi, M., Liu, S., Wanotayan, R., Kuniyoshi, S., Yoshida, K., Mae, Y., Sharma, M.K
    • Publisher
      Edit. Chen,C.
  • [Book] 「放射線によるDNA損傷・修復と細胞死」「臨床放射線腫瘍学」2012

    • Author(s)
      松本義久
    • Total Pages
      40-44
    • Publisher
      南江堂
  • [Book] DNA Repair2011

    • Author(s)
      Kamdar, R.P., Matsumoto, Y
    • Total Pages
      477-502
    • Publisher
      Edit. Kruman, I

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Published: 2014-08-29  

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