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Study on rapid and hypersensitive screening of chemical genotoxin using mammalian cells defective for DNA damage-response factors

Research Project

Project/Area Number 15K14953
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Biological pharmacy
Research InstitutionGakushuin University

Principal Investigator

HANAOKA Fumio  学習院大学, 理学部, 研究員 (50012670)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsゲノム / DNA損傷 / 損傷乗り越え合成 / 損傷応答 / 遺伝毒性 / スクリーニング系 / マウス胚性線維芽細胞 / DNAポリメラーゼ / DNA修復
Outline of Final Research Achievements

In order to establish a rapid, simple and hypersensitive method of screening various genotoxic compounds for mammalian cells, we compared sensitivities to various compounds among mouse embryonic fibroblasts derived from wild-type (WT) and knock-out mice lacking one of three Y-family TLS DNA polymerases (Pol eta, Pol iota, and Pol kappa) or all of them (TKO). We found that TKO cells exhibited the highest sensitivities to most of the tested genotoxins, but not to the non-genotoxins. Furthermore, we found that ratios of half-maximal inhibitory concentration of WT and TKO cells would be nice markers to quantitatively evaluate the hypersensitivity of TKO cells to different chemicals.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (26 results)

All 2018 2017 2016 2015 Other

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 11 results,  Acknowledgement Compliant: 7 results) Presentation (12 results) (of which Int'l Joint Research: 7 results,  Invited: 8 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites2018

    • Author(s)
      Yasuda Takeshi、Kagawa Wataru、Tajima Katsushi
    • Journal Title

      PLOS Genetics

      Volume: 14 Issue: 3 Pages: 1007277-1007277

    • DOI

      10.1371/journal.pgen.1007277

    • NAID

      120006459820

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hypersensitivity of mouse embryonic fibroblast cells defective for DNA polymerases η, ι and κ to various genotoxic compounds: Its potential for application in chemical genotoxic screening2018

    • Author(s)
      Akagi Jun-ichi、Yokoi Masayuki、Cho Young-Man、Toyoda Takeshi、Ohmori Haruo、Hanaoka Fumio、Ogawa Kumiko
    • Journal Title

      DNA Repair

      Volume: 61 Pages: 76-85

    • DOI

      10.1016/j.dnarep.2017.11.006

    • NAID

      120006456929

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Mcm2-7-interacting domain of human mini-chromosome maintenance 10 (Mcm10) protein is important for stable chromatin association and origin firing2017

    • Author(s)
      Izumi Masako、Mizuno Takeshi、Yanagi Ken-ichiro、Sugimura Kazuto、Okumura Katsuzumi、Imamoto Naoko、Abe Tomoko、Hanaoka Fumio
    • Journal Title

      Journal of Biological Chemistry

      Volume: 292 Issue: 31 Pages: 13008-13021

    • DOI

      10.1074/jbc.m117.779371

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Two mammalian homologs of yeast Rad23, HR23A and HR23B, as multifunctional proteins.2017

    • Author(s)
      Yokoi M, Hanaoka F
    • Journal Title

      Gene

      Volume: 597 Pages: 1-9

    • DOI

      10.1016/j.gene.2016.10.027

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Direct single-molecule observations of DNA unwinding by SV40 large tumor antigen under a negative DNA superhelical state.2017

    • Author(s)
      Takahashi S, Motooka S, Kawasaki S, Kurita H, Mizuno T, Matsuura SI, Hanaoka F, Mizuno A, Oshige M, Katsura S
    • Journal Title

      J Biomol Struct Dyn

      Volume: 5 Issue: 1 Pages: 1-13

    • DOI

      10.1080/07391102.2016.1269689

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 2,2,4-Triamino-5(2H)-oxazolone is a weak substrate for nucleotide excision repair.2016

    • Author(s)
      Kino K, Sugasawa K, Miyazawa H, Hanaoka F
    • Journal Title

      J Pharm Negative Results

      Volume: 7 Issue: 1 Pages: 42-45

    • DOI

      10.4103/0976-9234.177068

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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] SUMOylation of xeroderma pigmentosum group C protein regulates DNA damage recognition during nucleotide excision repair2015

    • Author(s)
      Akita M
    • Journal Title

      Sci. Rep.

      Volume: 5 Issue: 1 Pages: 10984-10984

    • DOI

      10.1038/srep10984

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The protein level of Rev1, a TLS polymerase in fission yeast, is strictly regulated during the cell cycle and after DNA damage.2015

    • Author(s)
      Uchiyama M, Terunuma J, Hanaoka F
    • Journal Title

      PLoS One

      Volume: 10 Issue: 7 Pages: e0130000-e0130000

    • DOI

      10.1371/journal.pone.0130000

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Different types of interaction between PCNA and PIP boxes contribute to distinct cellular functions of Y-family DNA polymerases.2015

    • Author(s)
      Masuda Y, Kanao R, Kaji K, Ohmori H, Hanaoka F, Masutani C
    • Journal Title

      Nucleic Acids Res

      Volume: 43 Issue: 16 Pages: 7898-7910

    • DOI

      10.1093/nar/gkv712

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] USP7 is a suppressor of PCNA ubiquitination and oxidative-stress-induced mutagenesis in human cells.2015

    • Author(s)
      Kashiwaba S, Kanao R, Masuda Y, Kusumoto-Matsuo R, Hanaoka F, Masutani C
    • Journal Title

      Cell Rep

      Volume: 13 Issue: 10 Pages: 2072-2080

    • DOI

      10.1016/j.celrep.2015.11.014

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] My CV: From our studies on XP-C to XP-V2017

    • Author(s)
      Hanaoka F
    • Organizer
      6th US-Japan DNA Repair Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] シスプラチン処理した細胞においてヒトDNAポリメラーゼηの働きに寄与するクロマチン構造変換因子2017

    • Author(s)
      横井雅幸、菅澤薫、花岡文雄
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] TLS polymerases and mutagenesis2017

    • Author(s)
      Hanaoka F
    • Organizer
      ICEM-ACEM 2017 Satellite Synposium on DNA Repair
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] シスプラチン誘発DNA鎖内架橋の乗り越え合成に関わるヒストン修飾酵素とクロマチン構造変換因子の探索2017

    • Author(s)
      横井雅幸、鹿谷有由希、菅澤薫、花岡文雄
    • Organizer
      第24回DNA複製・組換え・修復ワークショップ
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒトMCM10のMCM2-7相互作用ドメインの同定2017

    • Author(s)
      泉雅子、水野武、柳憲一郎、杉村和人、奥村克純、今本尚子、阿部知子、花岡文雄
    • Organizer
      第24回DNA複製・組換え・修復ワークショップ
    • Related Report
      2017 Annual Research Report
  • [Presentation] Mutant analyses of human DNA polymerase eta based on high-resolution crystal structures of the protein-DNA-dNTP complex.2016

    • Author(s)
      Hanaoka F, Yokoi M, Masutani C, Yang W
    • Organizer
      4th International Meeting on DNA Polymerases
    • Place of Presentation
      Biarritz, France
    • Year and Date
      2016-10-04
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Cancer and translesion synthesis polymerases.2016

    • Author(s)
      Sakurai Y, Yokoi M, Hanaoka F
    • Organizer
      2016 Cold Spring Harbor Asia Conference-DNA Metabolism,Genomic Stability and Diseases
    • Place of Presentation
      Suzhou, China
    • Year and Date
      2016-06-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 総括2015

    • Author(s)
      花岡文雄
    • Organizer
      BMB2015 ワークショップ「放射線生物影響の課題に挑む分子生物学研究の力」
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 私のDNA修復研究:XPCからXPVへ.2015

    • Author(s)
      花岡文雄
    • Organizer
      新学術領域研究「ゲノム普遍的制御」終了シンポジウム:ゲノム安定性の機構と生命の維持 -進化、癌化、老化の理解のために
    • Place of Presentation
      京都
    • Year and Date
      2015-08-29
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Structural and biochemical analyses for accommodation and recognition of UV-damaged bases within nucleosome.2015

    • Author(s)
      Osakabe A, Tachiwana H, Kagawa W, Horikoshi N, Matsumoto S, Yamamoto J, Hanaoka F, Sugasawa K, Iwai S, Kurumizaka H
    • Organizer
      「クロマチン動構造」国際シンポジウム
    • Place of Presentation
      淡路島、兵庫
    • Year and Date
      2015-08-23
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Regulation of the protein level of Rev1 in fission yeast.2015

    • Author(s)
      Uchiyama M, Terunuma J, Hanaoka F
    • Organizer
      Genomic Integrity, ZING Conference 2015
    • Place of Presentation
      Cairns, Australia
    • Year and Date
      2015-08-01
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Forty years of DNA damage tolerance.2015

    • Author(s)
      Hanaoka F
    • Organizer
      15th International Congress of Radiation Research (ICRR 2015)
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2015-05-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] DNA Replication, Recombination, and Repair-Molecular Mechanisms and Pathology2016

    • Author(s)
      Hanaoka F, Sugasawa K
    • Total Pages
      555
    • Publisher
      Springer Japan
    • Related Report
      2016 Research-status Report
  • [Book] DNA Replication, Recombination, and Repair: Molecular Mechanisms and Pathology2016

    • Author(s)
      Hanaoka F, Sugasawa K
    • Total Pages
      555
    • Publisher
      Springer, Japan
    • Related Report
      2015 Research-status Report
  • [Remarks] 学習院大学 花岡研究室

    • URL

      http://www-cc.gakushuin.ac.jp/~20080213

    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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