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Elucidation of the molecular mechanism that regulates homologous recombination and its applications to personalized radiotherapy for cancer

Research Project

Project/Area Number 20591492
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionThe University of Tokyo

Principal Investigator

HOSOYA Noriko  The University of Tokyo, 大学院・医学系研究科, 助教 (00396748)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsがん / 相同組換え / 放射線治療 / 放射線 / 癌 / 薬剤反応性 / 遺伝子
Research Abstract

In order to develop an effective personalized radiotherapy for cancer according to the DNA repair status of individual patients, it is important to clarify the molecular mechanisms that regulate the DNA damage repair systems. In this study, we investigated the mitotic role of the synaptonemal complex protein SYCP3, which is not expressed in normal mitotic cells but aberrantly expressed in cancer cells. We found that SYCP3 inhibits the intrinsic homologous recombination pathway by interfering with BRCA2, leading to hypersensitivity to radiation.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (54 results)

All 2011 2010 2009 2008

All Journal Article (22 results) (of which Peer Reviewed: 18 results) Presentation (31 results) Book (1 results)

  • [Journal Article] Single-stranded DNA catenation mediated by human EVL and a type I topoisomerase.2010

    • Author(s)
      Takaku M, Takahashi D, Machida S, Ueno H, Hosoya N, Ikawa S, Miyagawa K, Shibata T, Kurumizaka H
    • Journal Title

      Nucleic Acids Res 38(21)

      Pages: 7579-7586

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] DNA損傷修復とがん治療2010

    • Author(s)
      細谷紀子、宮川清
    • Journal Title

      がん分子標的療法 8(2)

      Pages: 26-35

    • Related Report
      2010 Final Research Report
  • [Journal Article] DNA損傷修復研究に基づくがん治療2010

    • Author(s)
      細谷紀子、宮川清
    • Journal Title

      放射線生物研究 45(1)

      Pages: 1-11

    • NAID

      40017079919

    • Related Report
      2010 Final Research Report
  • [Journal Article] Erdheim-Chester disease : multisystem involvement and management with interferon-α.2010

    • Author(s)
      Suzuki HI, Hosoya N, Miyagawa K, Ota S, Nakashima H, Makita N, Kurokawa M
    • Journal Title

      Leukemia Research 34(1)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 放射線によって生じるDNA二本鎖切断を修復する経路2010

    • Author(s)
      細谷紀子、宮川清
    • Journal Title

      細胞工学 29(1)

      Pages: 21-27

    • Related Report
      2010 Final Research Report
  • [Journal Article] Single-stranded DNA catenation mediated by human EVL and a type I topoisomerase.2010

    • Author(s)
      Takaku M, Takahashi D, Machida S, Ueno H, Hosova N, Ikawa S, Miyagawa K, Shibata T, Kurumizaka H.
    • Journal Title

      Nucleic Acids Res

      Volume: 38 Pages: 7579-7586

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DNA損傷修復とがん治療2010

    • Author(s)
      細谷紀子、宮川清
    • Journal Title

      がん分子標的療法

      Volume: 8 Pages: 26-35

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Erdheim-Chester disease : multisystem involvement and management with interferon-alpha.2010

    • Author(s)
      Suzuki Hl, Hosoya N, Miyagawa K, Ota S, Nakashima H, et el.
    • Journal Title

      Leuk Res 34

      Pages: 21-24

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recombination activator function of the novel RAD51- and RAD51B-binding protein, Human EVL.2009

    • Author(s)
      Takaku M, Machida S, Hosoya N, Nakayama S, Takizawa Y, Sakane I, Shibata T, Miyagawa K, Kurumizaka H
    • Journal Title

      J Biol Chem 284(21)

      Pages: 14326-14336

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinical importance of DNA repair inhibitors in cancer therapy.2009

    • Author(s)
      Hosoya N, Miyagawa K
    • Journal Title

      Magazine of European Medical Oncology 2

      Pages: 9-14

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional evidence for Eme1 as a marker of cisplatin resistance.2009

    • Author(s)
      Tomoda Y, Katsura M, Okajima M, Hosoya N, Kohno N, Miyagawa K
    • Journal Title

      Int J Cancer 124(12)

      Pages: 2997-3001

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional evidence for Emel as a marker of cisplatin resistance.2009

    • Author(s)
      Tomoda Y, Katsura M, Okajima M, Hosoya N, Kohno N, Miyagawa K.
    • Journal Title

      Int J Cancer 124

      Pages: 2997-3001

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recombination activator function of the novel RAD51- and RAD51B-binding protein, Human EVL.2009

    • Author(s)
      Takaku M, Machida S, Hosoya N, Nakayama S, Takizawa Y, et al.
    • Journal Title

      J Biol Chem 284

      Pages: 14326-14336

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recombination activator function of the novel RAD51- and RAD51B-binding Protein, Human EVL.2009

    • Author(s)
      Takaku M, Machida S, Hosoya N, Nakavama S, Takizawa Y, et al.
    • Journal Title

      J Biol Chem (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical importance of DNA repair inhibitors in cancer therapy.2009

    • Author(s)
      Hosova N, Miyagawa K.
    • Journal Title

      Magazine of European Medical Oncology 2

      Pages: 9-14

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional evidence for Emel as amarker of cisplatin resistance.2009

    • Author(s)
      Tomoda Y, Katsura M, 0kajima M, Hosoya N, Kohno N, Miyagawa K.
    • Journal Title

      Int J Cancer 124

      Pages: 2997-3001

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Herpes simplex encephalitis and subsequent cytomegalovirus encephalitis after chemoradiotherapy for central nervous system lymphoma : a case report and literature review.2008

    • Author(s)
      Suzuki HI, Hangaishi A, Hosoya N, Watanabe T, Kanda Y, Motokura T, Chiba S, Kurokawa M
    • Journal Title

      Int J Hematol. 87(5)

      Pages: 538-541

    • NAID

      10021256638

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinical features of late cytomegalovirus infection after hematopoietic stem cell transplantation.2008

    • Author(s)
      Asano-Mori Y, Kanda Y, Oshima K, Kako S, Shinohara A, Nakasone H, Sato H, Watanabe T, Hosoya N, Izutsu K, Asai T, Hangaishi A, Motokura T, Chiba S, Kurokawa M
    • Journal Title

      Int J Hematol. 87(3)

      Pages: 310-318

    • NAID

      10021256200

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Long-term ultra-low-dose acyclovir against varicella-zoster virus reactivation after allogeneic hematopoietic stem cell transplantation.2008

    • Author(s)
      Asano-Mori Y, Kanda Y, Oshima K, Kako S, Shinohara A, Nakasone H, Sato H, Watanabe T, Hosoya N, Izutsu K, Asai T, Hangaishi A, Motokura T, Chiba S, Kurokawa M
    • Journal Title

      Am J Hematol. 83(6)

      Pages: 472-476

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Herpes simplex encephalitis and subsequent cytomegalovirus encephalitis after chemoradiotherapy for central nervous system lymphoma: a case report and Iiterature review.2008

    • Author(s)
      Suzuki HI, Hangaishi A, Hosoya N, Watanabe T, Kanda Y, Motokura T, Chiba S, Kurokawa M.
    • Journal Title

      Int J Hematol 87

      Pages: 538-541

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical features of late cytomegalovirus infection after hematopoietic stem ce11 transplantation.2008

    • Author(s)
      Asano-Mori Y, Kanda Y, Oshima K, Kako S, Shinohara A, Nakasone H, Sato H, Watanabe T, Hosoya N, et al.
    • Journal Title

      Int J Hematol 87

      Pages: 310-318

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term ultra-low-dose acyclovir against varice11a-zoster virus reactivation after allogeneic hematopoietic stem cell transplantation.2008

    • Author(s)
      Asano-Mori Y, Kanda Y, Oshima K, Kako S, Shinohara A, Nakasone H, Sato H, Watanabe T, Hosoya N, et al.
    • Journal Title

      Am J Hematol 83

      Pages: 472-476

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] The role of the meiosis-specific protein SYCP3 in inducing genomic instability and implications for cancer therapy.2011

    • Author(s)
      Hosoya N, Miyagawa K
    • Organizer
      2011 Keystone Symposia Conference (B4 : Genomic Instability and DNA Repair)
    • Place of Presentation
      Keystone Resort, Keystone, Colorado, USA
    • Year and Date
      2011-01-31
    • Related Report
      2010 Final Research Report
  • [Presentation] The role of the meiosis-specific protein SYCP3 in inducing genomic instability and implications for cancer therapy2011

    • Author(s)
      Hosoya N, Miyagawa K.
    • Organizer
      2011 Keystone Symposia Conference(Genomic Instability and DNA Repair)
    • Place of Presentation
      コロラド キーストンリゾート(アメリカ合衆国)
    • Year and Date
      2011-01-31
    • Related Report
      2010 Annual Research Report
  • [Presentation] A role for meiosis-specific proteins in regulating homologous recombination in cancer2010

    • Author(s)
      細谷紀子
    • Organizer
      日本放射線影響学会第53回大会 シンポジウム「DNA damage response and disease」
    • Place of Presentation
      京都テルサ(京都府 京都市)
    • Year and Date
      2010-10-21
    • Related Report
      2010 Final Research Report
  • [Presentation] A role for meiosis-specific proteins in regulating homologous recombination in cancer2010

    • Author(s)
      Hosoya N
    • Organizer
      日本放射線影響会第53回大会
    • Place of Presentation
      京都テルサ(京都府京都市)
    • Year and Date
      2010-10-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] がん精巣抗原の発現による染色体安定性の破綻(Impaired chromosome stability caused by aberrant expression of the cancer/testis antigens)2010

    • Author(s)
      細谷紀子、宮川清
    • Organizer
      第72回日本血液学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川県 横浜市)
    • Year and Date
      2010-09-24
    • Related Report
      2010 Final Research Report
  • [Presentation] がん精巣抗原の発現による染色体安定性の破綻2010

    • Author(s)
      細谷紀子、宮川清
    • Organizer
      第72回日本血液学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] シナプトネマ複合体形成分子SYCP3はがん細胞における内因性の相同組換え修復経路を抑制する(The synaptonemal complex protein SYCP3 inhibits the intrinsic homologous recombination pathway in cancer)2010

    • Author(s)
      細谷紀子、宮川清
    • Organizer
      第69回日本癌学会学術総会,大阪
    • Place of Presentation
      大阪国際会議場・リーガロイヤルホテル大阪(大阪府 大阪市)
    • Year and Date
      2010-09-22
    • Related Report
      2010 Final Research Report
  • [Presentation] シナプトネマ複合体形成分子SYCP3はがん細胞における内因性の相同組換え修復経路を抑制する2010

    • Author(s)
      細谷紀子、宮川清
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪国際会議場、リーガロイヤルホテル大阪(大阪府大阪市)
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] がん精巣抗原SYCP3による細胞核内での相同組換え修復蛋白の動態の制御機構2010

    • Author(s)
      細谷紀子、宮川清
    • Organizer
      第9回核ダイナミクス研究会
    • Place of Presentation
      ラフォーレ修善寺(静岡県 伊豆市)
    • Year and Date
      2010-05-27
    • Related Report
      2010 Final Research Report
  • [Presentation] がん精巣抗原SYCP3による細胞核内での相同組換え修復蛋白の動態の制御機構2010

    • Author(s)
      細谷紀子、宮川清
    • Organizer
      第9回核ダイナミクス研究会
    • Place of Presentation
      ラフォーレ修善寺(静岡県伊豆市)
    • Year and Date
      2010-05-27
    • Related Report
      2010 Annual Research Report
  • [Presentation] SYCP3 is a novel BRCA2-interacting protein that induces genomic instability in cancer2010

    • Author(s)
      細谷紀子,宮川清
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会
    • Place of Presentation
      神戸国際会議場・神戸ポートピアホテル(兵庫県 神戸市)
    • Related Report
      2010 Final Research Report
  • [Presentation] SYCP3 is a novel BRCA2-interacting protein that induces genomic instability in cancer2010

    • Author(s)
      細谷紀子, 宮川清
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸国際会議場、神戸ポートピアホテル(兵庫県神戸市)
    • Related Report
      2010 Annual Research Report
  • [Presentation] The meiosis-specific synaptonemal complex proteins modulate the intrinsic homologous recombination pathway in human cancer cells2009

    • Author(s)
      細谷紀子,西村智子、藤井義大、宮川清
    • Organizer
      第32回日本分子生物学会年会ワークショップ「3W8 相同組換え研究の新展開」
    • Place of Presentation
      パシフィコ横浜(神奈川県 横浜市)
    • Year and Date
      2009-12-11
    • Related Report
      2010 Final Research Report
  • [Presentation] 減数分裂期特異的相同組換えに関与する分子の体細胞における役割2009

    • Author(s)
      細谷記子, 西村智子, 藤井義大, 宮川清
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜市、パシフィコ横浜
    • Year and Date
      2009-12-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] SYCE2分子の体細胞での発現による放射線感受性と相同組換え修復への影響2009

    • Author(s)
      細谷紀子、宮川清
    • Organizer
      日本放射線影響学会第52回大会,広島
    • Place of Presentation
      広島市南区民文化センター(広島県 広島市)
    • Year and Date
      2009-11-12
    • Related Report
      2010 Final Research Report
  • [Presentation] SYCE2分子の体細胞での発現による放射線感受性と相同組換え修復への影響2009

    • Author(s)
      細谷紀子, 宮川清
    • Organizer
      日本放射線影響学会第52回大会
    • Place of Presentation
      広島市、南区民文化センター
    • Year and Date
      2009-11-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] DNA損傷修復システムの異常と腫瘍2009

    • Author(s)
      細谷紀子
    • Organizer
      広島大学 平成21年度第19回数理分子生命理学セミナー(兼 広島大学第10回CAPWRセミナー)
    • Place of Presentation
      広島大学(広島県 東広島市)
    • Year and Date
      2009-11-10
    • Related Report
      2010 Final Research Report
  • [Presentation] DNA損傷修復システムの異常と腫瘍2009

    • Author(s)
      細谷紀子
    • Organizer
      広島大学平成21年度第19回数理分子生命理学セミナー兼広島大学第10回CAPWRセミナー
    • Place of Presentation
      東広島市、広島大学
    • Year and Date
      2009-11-10
    • Related Report
      2009 Annual Research Report
  • [Presentation] SYCE2は放射線抵抗性を誘導する新規癌精巣抗原である2009

    • Author(s)
      細谷紀子、波多野裕明、宮川清
    • Organizer
      第71回日本血液学会総会
    • Place of Presentation
      国立京都国際会館(京都府 京都市)
    • Year and Date
      2009-10-24
    • Related Report
      2010 Final Research Report
  • [Presentation] SYCE2は放射線抵抗性を誘導する新規癌精巣抗原である2009

    • Author(s)
      細谷紀子, 波多野裕明, 宮川清
    • Organizer
      第71回日本血液学会総会
    • Place of Presentation
      京都市、国立京都国際会館
    • Year and Date
      2009-10-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] SYCE2は相同組換えの異常と放射線抵抗性を誘導する新規癌精巣抗原である(SYCE2 is a novel cancer/testis antigen that induces radioresistance by modulating homologous recombination pathway)2009

    • Author(s)
      細谷紀子、宮川清
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県 横浜市)
    • Year and Date
      2009-10-03
    • Related Report
      2010 Final Research Report
  • [Presentation] SYCE2は相同組換えの異常と放射線抵抗性を誘導する新規癌精巣抗原である2009

    • Author(s)
      細谷紀子、宮川清
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜市、パシフィコ横浜
    • Year and Date
      2009-10-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] The meiosis-specific synaptonemal complex protein SYCP3 is a cancer/testis antigen that increases radiosensitivity by reducing recombination in cancer.2009

    • Author(s)
      Hosoya N, Miyagawa K
    • Organizer
      The 11th International Wolfsberg Meeting on Molecular Radiation Biology/Oncology
    • Place of Presentation
      Wolfsberg Castle Conference Center, Ermatingen, Switzerland
    • Year and Date
      2009-06-27
    • Related Report
      2010 Final Research Report
  • [Presentation] 減数分裂期特異的相同組換えに関与する分子の体細胞における役割2008

    • Author(s)
      細谷紀子,西村智子、宮川清
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会,神戸
    • Place of Presentation
      神戸ポートアイランド(兵庫県 神戸市)
    • Year and Date
      2008-12-10
    • Related Report
      2010 Final Research Report
  • [Presentation] 減数分裂期特異的相同組換えに関与する分子の体細胞における役割2008

    • Author(s)
      細谷紀子,西村智子、宮川清
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸市、神戸ポートアイランド
    • Year and Date
      2008-12-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] 減数分裂期特異的な相同組換え関連分子の体細胞における役割2008

    • Author(s)
      細谷紀子、西村智子、宮川清
    • Organizer
      日本放射線影響学会第51回大会
    • Place of Presentation
      北九州国際会議場(福岡県 北九州市)
    • Year and Date
      2008-11-20
    • Related Report
      2010 Final Research Report
  • [Presentation] 減数分裂期特異的な相同組換え関連分子の体細胞における役割2008

    • Author(s)
      細谷紀子,西村智子、宮川清
    • Organizer
      日本放射線影響学会第51回大会
    • Place of Presentation
      北九州市、北九州国際会議場
    • Year and Date
      2008-11-20
    • Related Report
      2008 Annual Research Report
  • [Presentation] 減数分裂特異的分子SYCP3の体細胞での異所性発現は放射線感受性を増加させる(Expression of the meiosis-specific synaptonemal complex protein SYCP3 increases radiosensitivity in somatic cells)2008

    • Author(s)
      細谷紀子、西村智子、宮川清
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県 名古屋市)
    • Year and Date
      2008-10-28
    • Related Report
      2010 Final Research Report
  • [Presentation] 減数分裂特異的分子SYCP3の体細胞での異所性発現は放射線感受性を増加させる2008

    • Author(s)
      細谷紀子,西村智子、宮川清
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋市、名古屋国際会議場
    • Year and Date
      2008-10-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] 減数分裂特異的相同組換えに関与する分子の腫瘍における異所性発現の役割2008

    • Author(s)
      細谷紀子、宮川清
    • Organizer
      第70回日本血液学会総会
    • Place of Presentation
      国立京都国際会館(京都府 京都市)
    • Year and Date
      2008-10-11
    • Related Report
      2010 Final Research Report
  • [Presentation] 減数分裂特異的相同組換えに関与する分子の腫瘍における異所性発現の役割2008

    • Author(s)
      細谷紀子、宮川清
    • Organizer
      第70回日本血液学会総会
    • Place of Presentation
      京都市、国立京都国際会館
    • Year and Date
      2008-10-11
    • Related Report
      2008 Annual Research Report
  • [Book] 抗がん剤の種類と特徴(エキスパートナース がん治療・ケア 実践ガイド part 2)2009

    • Author(s)
      細谷紀子
    • Publisher
      照林社
    • Related Report
      2010 Final Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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