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Analyses of oxidative stress-dependent formation of MUTYH/MutSalpha complex

Research Project

Project/Area Number 26340025
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Risk sciences of radiation and chemicals
Research InstitutionKyushu University

Principal Investigator

NAKATSU Yoshimichi  九州大学, 医学研究院, 准教授 (00207820)

Research Collaborator HAYASHIDA Genki  九州大学, システム生命学府
SONG Yingxia  九州大学, 医学系学府
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsミスマッチ修復 / 細胞死 / DNA損傷 / 8-オキソグアニン / 酸化ストレス / 複合体
Outline of Final Research Achievements

We observed an oxidative stress-dependent complex formation of MUTYH and mismatch repair factors. Using anti-FLAG antibody, we purified the complex from FLAG-tagged MUTYH expressing human cells. Western blot analyses revealed that the complex contained DNA polymerase δ and MLH 1 in addition to MSH 2, MSH 6, and PCNA. The interaction between MUTYH and MSH2 was also observed in the 8-oxo-dGua administered cells, suggesting that 8-oxoG is involved in the formation of this complex. In cells loaded with oxidative stress, transient mono-ubiquitination of PCNA occurs, but PCNA in this complex has not undergone ubiquitination. Certain MSH2 mutants found in Lynch syndrome and a DNA polymerase δ mutant do not form the oxidative stress-dependent complexes with MUTYH. These results suggested that DNA polymerase δ as well as MSH2 might be involved in molecular mechanisms underlying oxidative stress induced cell-death.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (40 results)

All 2017 2016 2015 2014

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Open Access: 11 results,  Acknowledgement Compliant: 2 results) Presentation (28 results) (of which Int'l Joint Research: 3 results,  Invited: 5 results) Book (1 results)

  • [Journal Article] Celecoxib and 2,5-dimethylcelecoxib inhibit intestinal cancer growth by suppressing the Wnt/β-catenin signaling pathway2017

    • Author(s)
      I. Egashira, F. Takahashi-Yanaga, R. Nishida, M. Arioka, K. Igawa, K. Tomooka, Y. Nakatsu, T. Tsuzuki, Y. Nakabeppu, T. Kitazono, T. Sasaguri,
    • Journal Title

      Cancer Science

      Volume: 108 Issue: 1 Pages: 108-115

    • DOI

      10.1111/cas.13106

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Insertion and deletion mismatches distant from the target position improve gene correction with a tailed duplex.2016

    • Author(s)
      H. Kamiya*, N. Nishigaki, A. Ikeda, S. Yukawa, Y. Morita, Y. Nakatsu, T. Tsuzuki and H. Harashima
    • Journal Title

      Nucleosides Nucleotides Nucleic Acids

      Volume: 35 Issue: 7 Pages: 379-388

    • DOI

      10.1080/15257770.2016.1163384

    • NAID

      120006313423

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] BUBR1 insufficiency in mice increases their sensitivity to oxidative stress2016

    • Author(s)
      Matsuda, D., Matsumoto, T., Honma, K., Ikawa-Yoshida, A., Onimaru, M., Furuyama, T., Nakatsu, Y., Tsuzuki, T., Maehara, Y.
    • Journal Title

      In Vvo

      Volume: 30 Pages: 769-776

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] BubR1 Insufficiency Impairs Liver Regeneration in Aged Mice after Hepatectomy through Intercalated Disc Abnormality2016

    • Author(s)
      A. Ikawa-Yoshida, T. Matsumoto, S. Okano, Y. Aoyagi, Y. Matsubara, T. Furuyama, Y. Nakatsu, T. Tsuzuki, M. Onimaru, T. Ohkusa, M. Nomura, Y. Maehara,
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 32399-32399

    • DOI

      10.1038/srep32399

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] BTK gene targeting by homologous recombination using a helper-dependent adenovirus/adeno-associated virus hybrid vector.2016

    • Author(s)
      Yamamoto H, Ishimura M, Ochiai M, Takada H, Kusuhara K, Nakatsu Y, Tsuzuki T, Mitani K, Hara T.
    • Journal Title

      Gene Ther

      Volume: 23 Issue: 2 Pages: 205-13

    • DOI

      10.1038/gt.2015.91

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differentiation-inducing factor-3 inhibits intestinal tumor growth in vitro and in vivo.2015

    • Author(s)
      Kubokura N, Takahashi-Yanaga F, Arioka M, Yoshihara T, Igawa K, Tomooka K, Morimoto S, Nakatsu Y, Tsuzuki T, Nakabeppu Y, Matsumoto T, Kitazono T, Sasaguri T
    • Journal Title

      J Pharmacol Sci

      Volume: 127 Issue: 4 Pages: 446-455

    • DOI

      10.1016/j.jphs.2015.03.005

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] UV-induced mutations in epidermal cells of mice defective in DNA polymerase η and/or ι2015

    • Author(s)
      Kanao R, Yokoi M, Ohkumo T, Sakurai Y, Dotsu K, Kura S, Nakatsu Y, Tsuzuki T, Masutani C, Hanaoka F
    • Journal Title

      DNA Repair (Amsterdam)

      Volume: S1568-7864(15) Pages: 00042-7

    • DOI

      10.1016/j.dnarep.2015.02.006

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] BubR1 insufficiency inhibits neointimal hyperplasia through impaired vascular smooth muscle cell proliferation in mice2015

    • Author(s)
      Kyuragi, R., Matsumoto, T., Harada, Y., Saito, S., Onimaru, M., Nakatsu, Y., Tsuzuki, T., Nomura, M., Yonemitsu, Y., Maehara, Y.
    • Journal Title

      Arterioscler. Thromb. Vasc. Biol.

      Volume: 35 Issue: 2 Pages: 341-347

    • DOI

      10.1161/atvbaha.114.304737

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mismatch repair deficient mice show susceptibility to oxidative stress-induced intestinal carcinogenesis2014

    • Author(s)
      J. Piao, Y. Nakatsu, M. Ohno, K. Taguchi, T. Tsuzuki
    • Journal Title

      International Journal of Biological Sciences

      Volume: 10 Issue: 1 Pages: 73-79

    • DOI

      10.7150/ijbs.5750

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] DIF-1 inhibits tumor growth in vivo reducing phosphorylation of GSK-3beta and expressions of cyclin D1 and TCF7L2 in cancer model mice.2014

    • Author(s)
      Takahashi-Yanaga, F., Yoshihara, T., Jingushi, K., Igawa, K., Tomooka, K., Watanabe, Y., Morimoto, S., Nakatsu, Y., Tsuzuki, T., Nakabeppu, Y., and Sasaguri, T.
    • Journal Title

      Biochem Pharmacol

      Volume: N/A Issue: 3 Pages: 340-348

    • DOI

      10.1016/j.bcp.2014.03.006

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Abnormality in Wnt signaling is causatively associated with oxidative stress-induced intestinal tumorigenesis in MUTYH-null mice2014

    • Author(s)
      Isoda T, Nakatsu Y, Yamauchi K, Piao J, Yao T, Honda H, Nakabeppu Y, Tsuzuki T
    • Journal Title

      Int J Biol Sci

      Volume: 10 Issue: 8 Pages: 940-947

    • DOI

      10.7150/ijbs.9241

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Mutyh欠損マウスにおける酸化ストレスによる消化管腫瘍発生頻度上昇と特異的体細胞変異シグニチャーの解析2016

    • Author(s)
      鷹野典子、大野みずき、中津可道、中別府雄作、續輝久
    • Organizer
      日本分子生物学会第39回年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-12-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヒト細胞由来ミスマッチ修復遺伝子変異体の作製とその解析2016

    • Author(s)
      林田元気、中津可道、日高京子、藤兼亮輔、日高真純、釣本敏樹、續輝久
    • Organizer
      日本分子生物学会第39回年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-12-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] ミスマッチ修復欠損マウスを用いた新規生殖細胞変異の検出2016

    • Author(s)
      大野みずき、鷹野典子、佐々木史子、中津可道、續輝久
    • Organizer
      日本環境変異原学会第45回大会
    • Place of Presentation
      つくば
    • Year and Date
      2016-11-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] Development of assay systems to characterize the variants of mismatch repair factor MSH2 found in Lynch syndrome2016

    • Author(s)
      Hayashida, G., Nakatsu, Y., Hidaka, K., Fujikane, R., Hidaka, M., Tsurimoto, T., Tsuzuki, T.
    • Organizer
      The 10th International 3R (Replication, Recombination and Repair) Symposium
    • Place of Presentation
      松江
    • Year and Date
      2016-11-14
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Characterization of mismatch repair factor MSH2 variants found in Lynch syndrome2016

    • Author(s)
      林田元気、中津可道、日高京子、藤兼亮輔、日高真純、釣本敏樹、續輝久
    • Organizer
      日本放射線影響学会第59回大会
    • Place of Presentation
      広島
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] 酸化ストレスによる消化管腫瘍発生頻度上昇と特異的体細胞変異シグニチャー: Mutyh欠損マウスを用いた解析2016

    • Author(s)
      大野みずき、鷹野典子、中津可道、中別府雄作、續輝久
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヒト細胞を用いたミスマッチ修復因子MSH2の変異体の解析2016

    • Author(s)
      林田元気、中津可道、日高京子、藤兼亮輔、日高真純、續輝久
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] CRISPR/Cas9を用いたヒト細胞のミスマッチ修復因子への変異導入2016

    • Author(s)
      林田元気、中津可道、日高京子、 藤兼亮輔、日高真純、釣本敏樹、 續輝久
    • Organizer
      日本遺伝学会第88回大会
    • Place of Presentation
      三島
    • Year and Date
      2016-09-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] ミスマッチDNA修復系が体細胞および生殖細胞ゲノムにおよぼす影響2016

    • Author(s)
      鷹野典子、大野みずき、 佐々木史子、中津可道、續輝久
    • Organizer
      日本遺伝学会第88回大会
    • Place of Presentation
      三島
    • Year and Date
      2016-09-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] ミスマッチ修復因子MSH2の発現系の確立と変異体の解析2015

    • Author(s)
      林田 元気、中津 可道、日高 京子、藤兼 亮輔、日高 真純、釣本 敏樹、續 輝久
    • Organizer
      日本分子生物学会第38回年会・日本生化学会第88回大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Mutyh欠損マウスを用いた酸化ストレス誘発突然変異と発がんの解析2015

    • Author(s)
      鷹野典子、大野みずき、佐々木史子、山内一己、中別府雄作、中津可道、續輝久
    • Organizer
      日本分子生物学会第38回年会・日本生化学会第88回大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] 酸化ストレス誘発マウス小腸発がん実験から見えてきたこと2015

    • Author(s)
      中津可道
    • Organizer
      日本環境変異原学会第44回大会
    • Place of Presentation
      福岡
    • Year and Date
      2015-11-27
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] ミスマッチ修復欠損マウスにおける生殖細胞ゲノム変異の解析2015

    • Author(s)
      大野みずき、鷹野典子、佐々木史子、日高京子、中津可道、續輝久
    • Organizer
      日本環境変異原学会第44回大会
    • Place of Presentation
      福岡
    • Year and Date
      2015-11-27
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 酸化ストレス誘発消化管発がんと突然変異の抑制におけるMUTYHの役割2015

    • Author(s)
      大野みずき、鷹野典子、中津可道、中別府雄作、續輝久
    • Organizer
      日本癌学会第74回学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Role of the oxidative DNA damage repair system in somatic and germline mutations in mice2015

    • Author(s)
      Mizuki Ohno, Noriko Takano, Kunihiko Sakumi, Ryutaro Fukumura, Yuki Iwasaki, Toshimichi Ikemura, Yoichi Gondo, Yusaku Nakabeppu, Yoshimichi Nakatsu, Teruhisa Tsuzuki
    • Organizer
      Zing conference "Genome Integrity"
    • Place of Presentation
      Cairns, Australia
    • Year and Date
      2015-07-31
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Mismatch Repair Deficient Mice Show Susceptibility to Oxidative Stress-induced Intestinal Carcinogenesis2015

    • Author(s)
      Yoshimich Nakatsu, Jingshu Piao, Takuya Hashizume, Mizuki Ohno, Kenichi Taguchi, Teruhisa Tsuzuki
    • Organizer
      15th International Congress of Radiation Research
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2015-05-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Oxidative stress-induced intestinal tumors in Mutyh-deficient mice treated with low doses of potassium bromate2014

    • Author(s)
      Teruhisa Tsuzuki, Mizuki Ohno, Noriko Takano, Kenichi Taguchi, Yusaku Nakabeppu, Yasunobu Aoki, Takehiko Nohmi, Yoshimichi Nakatsu
    • Organizer
      4th Asian Conference on Environmental Mutagen
    • Place of Presentation
      Kolkata, India
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Mutyh遺伝子欠損マウスを用いた酸化ストレス誘発消化管がんの解析2014

    • Author(s)
      大野みずき、鷹野典子、佐々木史子、田口健一、中別府雄作、青木康展、能美健彦、中津可道、續輝久
    • Organizer
      日本環境変異原学会第43回大会
    • Place of Presentation
      東京
    • Year and Date
      2014-12-04 – 2014-12-05
    • Related Report
      2014 Research-status Report
  • [Presentation] Mutyh遺伝子欠損マウスにおける酸化ストレス誘発突然変異の解析2014

    • Author(s)
      鷹野典子、大野みずき、稲葉洋平、志村勉、欅田尚樹、中別府雄作、中津可道、續輝久
    • Organizer
      日本環境変異原学会第43回大会
    • Place of Presentation
      東京
    • Year and Date
      2014-12-04 – 2014-12-05
    • Related Report
      2014 Research-status Report
  • [Presentation] Mutyh遺伝子欠損マウスにおける酸化ストレス誘発突然変異の解析2014

    • Author(s)
      鷹野典子、大野みずき、稲葉洋平、志村勉、欅田尚樹、中別府雄作、中津可道、續輝久
    • Organizer
      日本分子生物学会第37回年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 非標的部位におけるミスマッチの配列変換(遺伝子修復)への影響2014

    • Author(s)
      西垣奈津希、池田彰弘、湯川誠也、守田由子、中津可道、續輝久、原島秀吉、紙谷浩之
    • Organizer
      日本分子生物学会第37回年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Oxidative stress-induced intestinal tumors in Mutyh-deficient mice treated with low doses of potassium bromate2014

    • Author(s)
      Teruhisa Tsuzuki, Mizuki Ohno, Noriko Takano, Kenichi Taguchi, Yusaku Nakabeppu, Yasunobu Aoki, Takehiko Nohmi, Yoshimichi Nakatsu
    • Organizer
      5th US-Japan DNA Repair Meeting
    • Place of Presentation
      Tokushima, Japan
    • Year and Date
      2014-10-28 – 2014-10-31
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 酸化ストレス誘発突然変異と消化管がん解析2014

    • Author(s)
      大野みずき、鷹野典子、佐々木史子、橋詰拓弥、李賛、田口健一、中別府雄作、中津可道、續輝久
    • Organizer
      日本放射線影響学会第57回大会
    • Place of Presentation
      鹿児島
    • Year and Date
      2014-10-01 – 2014-10-03
    • Related Report
      2014 Research-status Report
  • [Presentation] ミスマッチ修復欠損マウスにおける酸化ストレス誘発突然変異の解析2014

    • Author(s)
      橋詰拓弥、中津可道、大野みずき、佐々木史子、鷹野典子、續輝久
    • Organizer
      日本放射線影響学会第57回大会
    • Place of Presentation
      鹿児島
    • Year and Date
      2014-10-01 – 2014-10-03
    • Related Report
      2014 Research-status Report
  • [Presentation] DIF-1はGSK-3βのリン酸化抑制とcyclin D1 および TCF7L2の発現低下により抗腫瘍効果を発揮する2014

    • Author(s)
      高橋富美、中津可道、續輝久、中別府雄作、笹栗俊之
    • Organizer
      日本癌学会第73回学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] マイクロサテライト不安定性は変異導入を伴ってDNA 複製ストレス下で誘導される2014

    • Author(s)
      熱海悠子、片山琴絵、島村徹平、中津可道、益谷美都子、宮野悟、中釜斉、續輝久、吉岡研一
    • Organizer
      日本癌学会第73回学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 低用量臭素酸カリウムの飲水投与によりMutyh遺伝子欠損マウスの消化管で誘発された突然変異並びに発がんの解析2014

    • Author(s)
      大野みずき、鷹野典子、中津可道、中別府雄作、續輝久
    • Organizer
      日本癌学会第73回学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Mutyh欠損マウスにおける酸化ストレス誘発発がんおよび突然変異の解析2014

    • Author(s)
      鷹野典子, 大野みずき, 中別府雄作, 中津可道, 續輝久
    • Organizer
      日本遺伝学会第86回大会
    • Place of Presentation
      長浜
    • Year and Date
      2014-09-17 – 2014-09-19
    • Related Report
      2014 Research-status Report
  • [Book] 日本臨牀(増刊号)最新臨床大腸癌学 基礎研究から臨床応用へ (Ⅲ-2-(6))酸化DNA損傷と大腸発癌)2015

    • Author(s)
      續輝久、大野みずき、中津可道
    • Total Pages
      715
    • Publisher
      株式会社 日本臨牀社
    • Related Report
      2015 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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