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Biochemical study on the molecular mechanisms of induced mutagenesis and post-replication repair pathways

Research Project

Project/Area Number 24310040
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Risk sciences of radiation/Chemicals
Research InstitutionNagoya University

Principal Investigator

Masuda Yuji  名古屋大学, 医学系研究科(環医), 准教授 (30273866)

Co-Investigator(Renkei-kenkyūsha) MASUTANI Chikahide  名古屋大学, 環境医学研究所, 教授 (40241252)
Kanao Rie  名古屋大学, 環境医学研究所, 助教 (30542287)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywords複製後修復 / 損傷乗り越え DNA 合成 / 脱ユビキチン / PCNA / ポリユビキチン化 / 突然変異誘発 / 損傷乗り越えDNA合成 / ユビキチン / HLTF / RAD6-RAD18 / template switch
Outline of Final Research Achievements

Radiation and environmental mutagens induce mutations. To elucidate molecular mechanisms of the induced mutagenesis is one of the biggest issues in this field. A large fraction of the induced mutation is generated by a cellular process, post-replication repair pathway. In humans, cells have two sub-pathways. One is the error-prone pathway, translesion DNA synthesis (TLS). The other is the error-free, in principle, pathway, template switch (TS). The regulation of the pathway choice that is a crucial step for the maintenance of genetic stability is regulated by ubiquitination of PCNA. In this study, we established in vitro reconstitution systems for PCNA ubiquitination and deubiquitination, and analyzed molecular mechanisms of these biochemical reactions.

Report

(4 results)
  • 2015 Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (37 results)

All 2015 2014 2013 2012 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (25 results) (of which Invited: 2 results) Remarks (5 results)

  • [Journal Article] Relevance of simultaneous mono-ubiquitinations of multiple units of PCNA homo-trimers in DNA damage tolerance.2015

    • Author(s)
      Kanao R, Masuda Y, Deguchi S, Yumoto-Sugimoto M, Hanaoka F, Masutani C
    • Journal Title

      PLoS One

      Volume: 10 Issue: 2 Pages: e0118775-e0118775

    • DOI

      10.1371/journal.pone.0118775

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Guanine-5-carboxylcytosine base pairs mimic mismatches during DNA replication.2014

    • Author(s)
      Shibutani T, Ito S, Toda M, Kanao R, Collins LB, Shibata M, Urabe M, Koseki H, Masuda Y, Swenberg JA, Masutani C, Hanaoka F, Iwai S, Kuraoka I
    • Journal Title

      Scientific Reports

      Volume: 4 Issue: 1 Pages: 5220-5220

    • DOI

      10.1038/srep05220

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A novel ATM/TP53/p21-mediated checkpoint only activated by chronic γ-irradiation2014

    • Author(s)
      CAO Lili, KAWAI Hidehiko, SASATANI Megumi, IIZUKA Daisuke, MASUDA Yuji, INABA Toshiya, SUZUKI Keiji, OOTSUYAMA Akira, UMATA Toshiyuki, KAMIYA Kenji, SUZUKI Fumio
    • Journal Title

      PLoS One

      Volume: 9 Issue: 8 Pages: e104279-e104279

    • DOI

      10.1371/journal.pone.0104279

    • NAID

      120006986457

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Strand breakage of (6-4) photoproduct-containing DNA at neutral pH and its repair by the ERCC1-XPF protein complex2013

    • Author(s)
      Arichi N, Yamamoto J, Takahata C, Masuda Y, Kuraoka I, Iwai S
    • Journal Title

      Org. Biomol. Chem.

      Volume: 11 Issue: 21 Pages: 3526-3534

    • DOI

      10.1039/c3ob00012e

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel interplay between the Fanconi anemia core complex and ATR-ATRIP kinase during DNA cross-link repair2013

    • Author(s)
      J Tomida, A Itaya, T Shigechi, J Unno, E Uchida, M Ikura, Y Masuda, S Matsuda J Adachi, M Kobayashi, AR Meetei, Y Maehara, K Yamamoto K Kamiya, A Matsuura, T Matsuda. T Ikura, M Ishiai, M Takata
    • Journal Title

      Nucleic Acids Research

      Volume: VOL. 41 Issue: 14 Pages: 6930-6941

    • DOI

      10.1093/nar/gkt467

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] <i>In Vitro</i> Studies of Exchanges between Replicative and Translesion DNA Polymerases in the Eukaryotic Post-replication Repair Pathway2012

    • Author(s)
      Masuda Y*
    • Journal Title

      Genes and Environment

      Volume: 34 Issue: 2 Pages: 70-76

    • DOI

      10.3123/jemsge.34.70

    • NAID

      10030311492

    • ISSN
      1880-7046, 1880-7062
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] En bloc transfer of polyubiquitin chains to PCNA in vitro is mediated by two different human E2-E3 pairs2012

    • Author(s)
      Masuda Y
    • Journal Title

      Nucleic Acids Res.

      Volume: 40(20) Issue: 20 Pages: 10394-10407

    • DOI

      10.1093/nar/gks763

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] ヒト細胞におけるPCNAの翻訳後修飾によるDNA損傷トレランス制御機構の解析2015

    • Author(s)
      金尾梨絵, 増田雄司, 花岡文雄, 益谷央豪
    • Organizer
      平成26年度「がん研究分野の特性等を踏まえた支援活動」公開シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2015-01-27 – 2015-01-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] HECTタイプのユビキチンリガーゼ、E6AP-E6複合体によるユビキチン鎖伸長反応の分子機構2014

    • Author(s)
      増田雄司, 柊元 巌, 益谷央豪
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 変異体PCNA発現ヒト細胞を用いたDNA損傷トレランス制御の解析2014

    • Author(s)
      金尾梨絵, 増田雄司, 花岡文雄, 益谷央豪
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Interactions between PCNA and Y-family DNA polymerases2014

    • Author(s)
      Masuda Y, Kanao R, Ohmori H, Hanaoka F, Masutani C
    • Organizer
      The 9th 3R (Replication, Recombination and Repair) Symposium
    • Place of Presentation
      御殿場
    • Year and Date
      2014-11-17 – 2014-11-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] Relevance of simultaneous mono-ubiquitinations of multiple units of PCNA homo-trimers in DNA damage tolerance2014

    • Author(s)
      Masutani C, Kanao R, Masuda Y, Hanaoka F
    • Organizer
      The 9th 3R (Replication, Recombination and Repair) Symposium
    • Place of Presentation
      御殿場
    • Year and Date
      2014-11-17 – 2014-11-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] Analysis of a novel DNA-dependent ubiquitin ligase, human HLTF2014

    • Author(s)
      Matsumoto S, Masuda Y, Masutani C
    • Organizer
      The 9th 3R (Replication, Recombination and Repair) Symposium
    • Place of Presentation
      御殿場
    • Year and Date
      2014-11-17 – 2014-11-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] ユビキチンリガーゼによるユビキチン鎖リンケージとユビキチン鎖の伸長制御2014

    • Author(s)
      増田雄司
    • Organizer
      国立遺伝学研究所研究集会「染色体DNAの安定維持の分子メカニズム」
    • Place of Presentation
      三島
    • Year and Date
      2014-11-06 – 2014-11-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] DNAポリメラーゼηとPCNAの相互作用の解析2014

    • Author(s)
      増田雄司, 金尾梨絵, 大森治夫, 花岡文雄, 益谷央豪
    • 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 Annual Research Report
  • [Presentation] DNAポリメラーゼηのPCNA相互作用部位の解析2014

    • Author(s)
      増田雄司, 金尾梨絵, 大森治夫, 花岡文雄, 益谷央豪
    • 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 Annual Research Report
  • [Presentation] Different types of interactions between PCNA and Y-family DNA polymerases for translesion DNA synthesis2014

    • Author(s)
      Masud Y, Kanao R, Ohmori H, Hanaoka F, Masutani C
    • Organizer
      ZING conference, DNA Polymerases: Biology, Diseases and Biomedical Applications Conference 2014
    • Place of Presentation
      Cambridge, UK
    • Year and Date
      2014-08-31 – 2014-09-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] The short CCG run in Huntingtin (HTT) gene is an obstacle for replicative DNA polymerases, potentially hampering the fork progression2014

    • Author(s)
      Hang LP, Furukohri A, Masuda Y, Maki S, Katayama T, Maki H
    • Organizer
      ZING conference, DNA Polymerases: Biology, Diseases and Biomedical Applications Conference 2014
    • Place of Presentation
      Cambridge, UK
    • Year and Date
      2014-08-31 – 2014-09-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] PCNAのユビキチン修飾による複製後修復経路の制御2014

    • Author(s)
      増田雄司, 益谷央豪
    • Organizer
      変異機構研究会・第27回夏の学校
    • Place of Presentation
      小牧
    • Year and Date
      2014-06-21 – 2014-06-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] Two different types of interactions between PCNA and Y-family DNA polymerases have distinct roles for translesion DNA synthesis2014

    • Author(s)
      Y Masuda, R Kanao, H Ohmori, F Hanaoka, C Masutani
    • Organizer
      International Symposium on Xeroderma Pigmentosum and Related Diseases: Disorders of DNA Damage Response-Bench to Bedside-
    • Place of Presentation
      神戸国際会議場(神戸)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Yファミリ―DNAポリメラーゼとPCNAとの相互作用による損傷乗り越えDNA合成経路の制御2013

    • Author(s)
      増田雄司, 金尾梨絵, 益谷央豪
    • Organizer
      変異機構研究会・第26回夏の学校
    • Place of Presentation
      アイプラザ一宮(一宮)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Yファミリ―DNAポリメラーゼとPCNAとの相互作用の解析2013

    • Author(s)
      増田雄司, 金尾梨絵, 益谷央豪
    • Organizer
      日本遺伝学会第85回大会
    • Place of Presentation
      慶應義塾大学 日吉キャンパス(横浜)
    • Related Report
      2013 Annual Research Report
  • [Presentation] DNAポリメラーゼηとPCNAとの相互作用による損傷乗り越えDNA合成経路の制御2013

    • Author(s)
      増田雄司, 金尾梨絵, 益谷央豪
    • Organizer
      日本放射線影響学会第56回大会
    • Place of Presentation
      ホテルクラウンパレス青森 (青森)
    • Related Report
      2013 Annual Research Report
  • [Presentation] ヒトYファミリ―DNAポリメラーゼとPCNAとの相互作用2013

    • Author(s)
      増田雄司, 金尾梨絵, 益谷央豪
    • Organizer
      第22回DNA複製・組換え・修復ワークショップ
    • Place of Presentation
      ホテルニュー水戸屋(仙台)
    • Related Report
      2013 Annual Research Report
  • [Presentation] PCNAのユビキチン修飾による複製後修復経路の制御2013

    • Author(s)
      増田雄司
    • Organizer
      国立遺伝学研究所・研究会「染色体DNAの安定維持の分子メカニズム」
    • Place of Presentation
      国立遺伝学研究所(三島)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] En bloc transfer of poly-ubiquitin chains to PCNA in vitro, implication in regulation of post-replication repair pathway2012

    • Author(s)
      Masuda Y, Suzuki M, Kawai H, Hishiki A, Hashimoto H, Masutani, C, Hishida T, Suzuki F, Kamiya K
    • Organizer
      The 28th Radiation Biology Center International Symposium
    • Place of Presentation
      COOP Inn Kyoto (京都)
    • Year and Date
      2012-11-29
    • Related Report
      2012 Annual Research Report
  • [Presentation] En bloc transfer of poly-ubiquitin chains to PCNA in vitro is mediated by two different human E2-E3 pairs2012

    • Author(s)
      Masuda Y, Suzuki M, Kawai H, Hishiki A, Hashimoto H, Masutani C, Hishida T, Suzuki F, Kamiya K
    • Organizer
      The 8th 3R (Replication, Recombination and Repair) Symposium
    • Place of Presentation
      淡路夢舞台国際会議場(淡路)
    • Year and Date
      2012-11-26
    • Related Report
      2012 Annual Research Report
  • [Presentation] PCNAのユビキチン化の分子機構と複製後修復経路の制御2012

    • Author(s)
      増田雄司
    • Organizer
      日本環境変異原学会-変異機構研究会・第25回夏の学校
    • Place of Presentation
      小牧勤労センター(小牧)
    • Related Report
      2012 Annual Research Report
  • [Presentation] En bloc transfer of poly-ubiquitin chains to PCNA in vitro mediated by two human E2-E3 pairs2012

    • Author(s)
      Masuda Y
    • Organizer
      Mutagenesis, Gordon Research Conferences, A Delicate Balance : Cellular Mutation Pathways in Genetic Stability and Disease
    • Place of Presentation
      Salve Regina University (Newport, USA)
    • Related Report
      2012 Annual Research Report
  • [Presentation] ヒトPCNAのユビキチン化酵素RAD6-RAD18複合体の構造と機能2012

    • Author(s)
      増田雄司、鈴木美紀、益谷央豪、神谷研二
    • Organizer
      日本放射線影響学会第55回大会
    • Place of Presentation
      東北大学川内北キャンパス(仙台)
    • Related Report
      2012 Annual Research Report
  • [Presentation] PCNAのユビキチン化の新規分子機構2012

    • Author(s)
      増田雄司、益谷央豪
    • Organizer
      日本遺伝学会第84回大会
    • Place of Presentation
      九州大学医学部(福岡)(招待講演)
    • Related Report
      2012 Annual Research Report
  • [Presentation] ヒトPCNAのポリュビキチン化の新規分子機構2012

    • Author(s)
      増田雄司、鈴木美紀、河合秀彦、菱木麻美、橋本 博、益谷央豪、神谷研二
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場(福岡)
    • Related Report
      2012 Annual Research Report
  • [Remarks] 名古屋大学環境医学研究所

    • URL

      http://www.riem.nagoya-u.ac.jp

    • Related Report
      2014 Annual Research Report
  • [Remarks] 名古屋大学環境医学研究所ゲノム動態制御分野

    • URL

      http://www.riem.nagoya-u.ac.jp/4/genome/home.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 名古屋大学環境医学研究所

    • URL

      http://www.riem.nagoya-u.ac.jp

    • Related Report
      2013 Annual Research Report
  • [Remarks] 名古屋大学環境医学研究所ゲノム動態制御分野

    • URL

      http://www.riem.nagoya-u.ac.jp/4/genome/home.html

    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://www.riem.nagoya-u.ac.jp/

    • Related Report
      2012 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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