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Structural basis for molecular interactions in DNA damage tolerance

Research Project

Project/Area Number 25291017
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Structural biochemistry
Research InstitutionUniversity of Shizuoka

Principal Investigator

HASHIMOTO HIROSHI  静岡県立大学, 薬学部, 教授 (40336590)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2015: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
KeywordsX線結晶構造解析 / 構造生物学 / DNA修復 / DNA損傷
Outline of Final Research Achievements

DNA damage occurs both naturally and artificially. Damaged template DNA blocks accurate and processive DNA synthesis by replicative DNA polymerases, resulting in genomic instability which causes various diseases including cancer. To avoid replication arrest and to restart DNA synthesis, cells initiate DNA damage tolerance (DDT). DDT is divided into two pathways, translesion DNA synthesis (TLS) and template-switched DNA synthesis (TS). TLS is transient DNA synthesis using a damaged template by error-prone DNA polymerases specialized for DNA damage. TS, in which one newly synthesized strand is utilized as an undamaged template for replication by replicative polymerases, is an error-free process. In this study, we performed structural analyses by x-ray crystallography and structure-based functional analyses of proteins involved in DDT, thereby clarifying the structural basis for molecular interactions in DDT. Our results could provide a clue to develop novel drugs for cancer therapy.

Report

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

    (29 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (19 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results) Remarks (1 results)

  • [Int'l Joint Research] St. Jude Children's Research Hospital/NIH(米国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Oxidative trans to cis Isomerization of Olefins in Polyketide Biosynthesis2016

    • Author(s)
      Tsuyoshi Yamamoto, Yuta Tsunematsu, Kodai Hara, Tomohiro Suzuki, Shinji Kishimoto, Hirokazu Kawaguchi, Hiroshi Noguchi, Hiroshi Hashimoto, Yi Tang, Kinya Hotta, & Kenji Watanabe
    • Journal Title

      Angew Chem Int Ed Engl

      Volume: 印刷中 Issue: 21 Pages: 6207-6210

    • DOI

      10.1002/anie.201600940

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Water-Binding Phospholipid Nanodomains and Phase-Separated Diacylglycerol Nanodomains Regulate Enzyme Reactions in Lipid Monolayers2015

    • Author(s)
      Teruyoshi Nagashima, Hiroshi Hashimoto, Satoshi Fuji, & Shogo Uematsu
    • Journal Title

      Langmuir

      Volume: 31 Issue: 17 Pages: 5014-5014

    • DOI

      10.1021/acs.langmuir.5b00996

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural Basis of New Allosteric Inhibition in Kinesin Spindle Protein Eg52015

    • Author(s)
      Yokoyama H, Sawada J, Katoh S, Matsuno K, Ogo N, Ishikawa Y, Hashimoto H, Fujii S, Asai A.
    • Journal Title

      ACS Chem. Biol.

      Volume: 10 Issue: 4 Pages: 1128-1136

    • DOI

      10.1021/cb500939x

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Crystallographic study of a novel DNA-binding domain of human HLTF involved in the template-switching pathway to avoid the replication arrest caused by DNA damage2015

    • Author(s)
      Yuzu Ikegaya, Kodai Hara, Asami Hishiki, Hideshi Yokoyama, & Hiroshi Hashimoto
    • Journal Title

      Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun.

      Volume: 印刷中 Issue: 6 Pages: 668-670

    • DOI

      10.1107/s2053230x15005907

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure of a Novel DNA-binding Domain of Helicase-like Transcription Factor (HLTF) and Its Functional Implication in DNA Damage Tolerance2015

    • Author(s)
      Asami Hishiki, Kodai Hara, Yuzu Ikegaya, Hideshi Yokoyama, Toshiyuki Shimizu, Mamoru Sato, & Hiroshi Hashimoto
    • Journal Title

      J Biol Chem

      Volume: 印刷中

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 小角散乱と結晶構造の複合構造解析2014

    • Author(s)
      小田 隆, 橋本 博
    • Journal Title

      日本結晶学会誌

      Volume: 56 Pages: 247-252

    • NAID

      130004688357

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Small Molecule Inhibitor of Monoubiquitinated Proliferating Cell Nuclear Antigen (PCNA) inhibits Repair of Interstrand DNA Crosslink, enhances DNA Double-strand Break, and sensitizes Cancer Cells to Cisplatin2014

    • Author(s)
      Akira Inoue, Sotaro Kikuchi, Asami Hishiki, Youming Shao, Richard Heath, Benjamin J. Evison, Marcelo Actis, Christine E. Canman, Hiroshi Hashimoto, & Naoaki Fujii
    • Journal Title

      J. Biol. Chem

      Volume: 289 Issue: 10 Pages: 7109-7120

    • DOI

      10.1074/jbc.m113.520429

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Missense Mutation in Rev7 Disrupts Formation of Polζ, Impairing Mouse Development and Repair of Genotoxic Agent-induced DNA Lesions2014

    • Author(s)
      Maryam Khalaj, Abdolrahim Abbasi, Hiroshi Yamanishi, Kouyou Akiyama, Shuso Wakitani, Sotaro Kikuchi, Michiko Hirose, Misako Yuzuriha, Masaki Magari, Heba A Degheidy, Kuniya Abe, Atsuo Ogura, Hiroshi Hashimoto, & Tetsuo Kunieda
    • Journal Title

      J Biol Chem

      Volume: 289 Issue: 6 Pages: 3811-3824

    • DOI

      10.1074/jbc.m113.514752

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] オリゴペプチド結合タンパク質の精製と結晶化2016

    • Author(s)
      亀井 七海、横山 英志、小西 佳史郎、原 幸大、石川 吉伸、松井 郁夫、Patrick FORTERRE、橋本 博
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] Mad2L2とIpaBの相互作用に関する構造生物学的研究2016

    • Author(s)
      田原迫 奨大、菊池 壮太郎、原 幸大、横山 英志、清水 敏之、佐藤 衛、橋本 博
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] PCNA-ZRANB3 PIP 複合体の構造解析2016

    • Author(s)
      内田 雅之、田形 梨紗、原 幸大、横山 英志、橋本 博
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] Mechanistic Study on the generation of carbon monoxide from phenyl formate and its application to the development of Pd-catalyzed carbonylation at room temperature2015

    • Author(s)
      Hideyuki Konishi, Mika Matsubara, Keisuke Mori, Yoshinobu Ishikawa, Hiroshi Hashimoto, Hiroaki Tokiwa, Kei Manabe
    • Organizer
      2015 International Chemical Congress of Pacific Basin Societies
    • Place of Presentation
      Honolulu, USA
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Structure and function of REV7 as the adaptor protein of REV1 and REV3 polymerases2015

    • Author(s)
      Hiroshi Hashimoto
    • Organizer
      15th International Congress of Radiation Research (ICRR2015)
    • Place of Presentation
      Kyoto
    • Year and Date
      2015-05-25 – 2015-05-29
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] ギ酸誘導体の一酸化炭素生成機構およびこれを用いる実用的有機合成反応2014

    • Author(s)
      小西 英之、上田 剛、松原 美香、森 敬介、石川 吉伸、橋本 博、常盤 広明、眞鍋 敬
    • Organizer
      第40回反応と合成の進歩シンポジウム
    • Place of Presentation
      仙台
    • Year and Date
      2014-11-10 – 2014-11-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] 赤痢菌IpaBによるMad2L2の機能阻害複合体の結晶学的研究2014

    • Author(s)
      片川 裕理、原 幸大、花岡 佑樹、菊池 壮太郎、横山 英志、Kim Minsoo、笹川 千尋、佐藤 衛、橋本 博
    • Organizer
      平成26年度日本結晶学会年会
    • Place of Presentation
      東京
    • Year and Date
      2014-11-01 – 2014-11-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] 膜タンパク質ストマチン特異的切断プロテアーゼの構造生物学的研究2014

    • Author(s)
      鈴木 佳奈、横山 英志、原 幸大、松井 郁夫、橋本 博
    • Organizer
      平成26年度日本結晶学会年会
    • Place of Presentation
      東京
    • Year and Date
      2014-11-01 – 2014-11-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] 膜小胞形成に関わるオリゴペプチド結合タンパク質の調製と結晶化2014

    • Author(s)
      小西 佳史郎、横山 英志、原 幸大、石川 吉伸、松井 郁夫、Patrick Forterre、橋本 博
    • Organizer
      平成26年度日本結晶学会年会
    • Place of Presentation
      東京
    • Year and Date
      2014-11-01 – 2014-11-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] キネシンEg5と ATP競合阻害剤との複合体の結晶構造2014

    • Author(s)
      横山英志、澤田潤一、加藤詩織、松野研司、小郷尚久、石川吉伸、藤井敏、浅井章良、橋本 博
    • Organizer
      平成26年度日本結晶学会年会
    • Place of Presentation
      東京
    • Year and Date
      2014-11-01 – 2014-11-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] RAD5のN末端ドメインの試料調製2014

    • Author(s)
      橋本 博
    • Organizer
      USフォーラム
    • Place of Presentation
      静岡
    • Year and Date
      2014-09-25 – 2014-09-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 塩基によるギ酸エステルの分解反応の計算化学的解析2014

    • Author(s)
      森 敬介、小西 英之、石川 吉伸、橋本 博、眞鍋 敬
    • Organizer
      第60回日本薬学会東海支部大会
    • Place of Presentation
      鈴鹿
    • Year and Date
      2014-07-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] 修復・転写・細胞周期に関わるMad2L2シグナリング複合体の構造生物学2014

    • Author(s)
      橋本 博
    • Organizer
      新学術領域「構造細胞生物学」班会議
    • Place of Presentation
      北海道
    • Year and Date
      2014-06-14 – 2014-06-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] 細胞周期を制御するREV7/Mad2l2と赤痢菌IpaBとの相互作用の構造基盤2013

    • Author(s)
      菊池壮太郎、原幸大、清水敏之、佐藤衛、橋本博
    • Organizer
      日本結晶学会年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] Structural study of REV7, the adaptor protein coordinating REV1 and REV3 polymerases in translesion DNA synthesis2013

    • Author(s)
      Sotato Kikuchi, Kodai Hara, Toshiyuki Shimizu, Mamoru Sato, Hiroshi Hashimoto
    • Organizer
      Structural Life Science 7th International Conference on Structural Genomics
    • Place of Presentation
      sapporo
    • Related Report
      2013 Annual Research Report
  • [Presentation] 修復・転写・細胞周期に関わるMad2L2シグナリング複合体の構造生物学2013

    • Author(s)
      橋本博
    • Organizer
      新学術領域「構造細胞生物学」班会議
    • Place of Presentation
      山梨
    • Related Report
      2013 Annual Research Report
  • [Presentation] REV7-REV3複合体構造から示唆される REV7/Mad2L2と赤痢菌タンパク質 IpaB との相互作用2013

    • Author(s)
      菊池壮太郎、原幸大、清水敏之、佐藤衛、橋本博
    • Organizer
      日本蛋白質科学会年会
    • Place of Presentation
      鳥取
    • Related Report
      2013 Annual Research Report
  • [Presentation] DNA損傷があっても複製を続けるためのDNAポリメラーゼ相互作用

    • Author(s)
      橋本博
    • Organizer
      X線の会
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 損傷乗り越えDNA合成におけるポリメラーゼ相互作用の構造基盤

    • Author(s)
      橋本博
    • Organizer
      NRGICがん・ゲノム重点セミナー
    • Place of Presentation
      長崎
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Remarks]

    • URL

      http://w3pharm.u-shizuoka-ken.ac.jp/bukka/

    • Related Report
      2014 Annual Research Report

URL: 

Published: 2013-05-21   Modified: 2022-01-27  

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