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Analysis of DNA topology, transcription and DNA repair

Research Project

Project/Area Number 26870867
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Molecular biology
Risk sciences of radiation and chemicals
Research InstitutionNational Institute of Health Sciences

Principal Investigator

Horibata Katsuyoshi  国立医薬品食品衛生研究所, 変異遺伝部, 主任研究官 (40402995)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords転写 / topoisomerase / DNA修復 / 複合体 / DNA損傷 / 内在性DNA損傷 / 脊髄小脳失調症 / DNAトポロジー / コケイン症候群
Outline of Final Research Achievements

DNA topoisomerase I (TOP1) is an essential enzyme involved in resolving the torsional stress associated with DNA replication and transcription. TOP1 have a deleterious effect on cells in these processes. In the event(s), when the final re-ligation step of the reaction cycle is prevented, the covalent TOP1-DNA intermediate becomes a toxic DNA lesion, called TOP1-DNA covalent complex (TOP1-cc). The molecular mechanisms of repair of TOP1-cc seem to be complicated with DNA replication, transcription, recombination and protein degradation. However, detailed mechanisms are not clear. Here we purified and analyzed TOP1 protein complexes to know molecular mechanisms of repair of TOP1-cc, TOP1 itself and interaction proteins. Additionally, we analyzed the localization of TOP1 on the target gene.

Report

(3 results)
  • 2017 Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (17 results)

All 2016 2015 2014

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Acknowledgement Compliant: 1 results,  Open Access: 1 results) Presentation (10 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Evaluation of mutagenicity of acrylamide using RBC Pig-a and PIGRET assays by single peroral dose in rats.2016

    • Author(s)
      Horibata K, Ukai A, Honma M
    • Journal Title

      Mutation Research

      Volume: in press Pages: 54-59

    • DOI

      10.1016/j.mrgentox.2015.12.005

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Measuring Reproducibility of Dose Response Data for the Pig-a Assay using Covariate Benchmark Dose Analysis.2016

    • Author(s)
      Johnson GE, Yamamoto M, Suzuki Y, Adachi H, Kyoya T, Takasawa H, Horibata K, Tsutsumi E, Wada K, Kikuzuki R, Yoshida I, Kimoto T, Maeda A, Narumi K
    • Journal Title

      Mutation Research

      Volume: in press

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The in vivo Pig-a assay: A report of the International Workshop On Genotoxicity Testing (IWGT) Workgroup2015

    • Author(s)
      Gollapudi BB, Lynch AM, Heflich RH, Dertinger SD, Dobrovolsky VN, Froetschl R, Horibata K, Kenyon MO, Kimoto T, Lovell DP, Stankowski Jr LF, White PA, Witt KL, Tanir JY.
    • Journal Title

      Mutation Research

      Volume: in press Pages: 23-35

    • DOI

      10.1016/j.mrgentox.2014.09.007

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Constructive rescue of TFIIH instability by an alternative isoform of XPD derived from a mutated XPD allele in mild but not severe XP-D/CS.2015

    • Author(s)
      Katsuyoshi Horibata, Sayaka Kono, Chie Ishigami, Xue Zhang, Madoka Aizawa, Yuko Kako, Takuma Ishii, Rika Kosaki, Masafumi Saijo and Kiyoji Tanaka
    • Journal Title

      J. Human Genetics

      Volume: 印刷中 Issue: 5 Pages: 259-265

    • DOI

      10.1038/jhg.2015.18

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Absence of in vivo genotoxicity of 3-monochloropropane-1,2-diol and associated fatty acid esters in a 4 week comprehensive toxicity study using F344 gpt delta rats2014

    • Author(s)
      Onami S, Cho YM, Toyoda T, Horibata K, Ishii Y, Umemura T, Honma M, Nohmi T, Nishikawa A, Ogawa K
    • Journal Title

      Mutagenesis

      Volume: 29 Issue: 4 Pages: 295-302

    • DOI

      10.1093/mutage/geu018

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nucleotide excision repair-dependent DNA double-strand break formation and ATM signaling activation in mammalian quiescent cells2014

    • Author(s)
      Mitsuo Wakasugi, Takuma Sasaki, Megumi Matsumoto, Miyuki Nagaoka, Keiko Inoue, Manabu Inobe, Katsuyoshi Horibata, Kiyoji Tanaka, and Tsukasa Matsunaga
    • Journal Title

      J. Biological Chemistry

      Volume: 289 Issue: 41 Pages: 28730-28737

    • DOI

      10.1074/jbc.m114.589747

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of Rats' <i>In Vivo</i> Genotoxicity Induced by <i>N</i>-ethyl-<i>N</i>-nitrosourea in the RBC <i>Pig-a</i>, PIGRET, and <i>gpt</i> Assays2014

    • Author(s)
      Horibata K, Ukai A, Honma M.
    • Journal Title

      Genes and Environment

      Volume: 36 Issue: 4 Pages: 199-202

    • DOI

      10.3123/jemsge.2014.023

    • NAID

      130004685140

    • ISSN
      1880-7046, 1880-7062
    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Pig-a/PIGRETアッセイの短期試験としての有用性:MMS共同研究報告2015

    • Author(s)
      堀端克良, 山田雅巳, 鵜飼明子, 木本崇文, 千藏さつき, 三浦大志郎, 伊東悟, 武藤重治, 宇野芳文, 真田尚和, 高島理恵,志賀野美幸,高沢博修, 濵田修一,山本美佳, 堀妃佐子, 堤絵梨, 和田邦生, 前田晃央, 菊月隆太, 荻原庸介, 京谷恭弘, 足立秀樹, 上松泰明, 吉田唯真, 成見香瑞範, 藤石洋平,福田隆之, 鈴木裕太, 後藤玄, 森田健, 本間正充
    • 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
  • [Presentation] Pig-a アッセイ2015

    • Author(s)
      堀端克良
    • Organizer
      哺乳動物試験研究会第67回定例会
    • Place of Presentation
      福岡
    • Year and Date
      2015-11-26
    • Related Report
      2015 Research-status Report
  • [Presentation] Interlaboratory Trial of the PIGRET Assay As a Short-term Genotoxicity Test: Collaborative Study by Mammalian Mutagenicity Study (MMS) Group of Japanese Environmental Mutagen Society (JEMS)2015

    • Author(s)
      Horibata K, Yamada M, Ukai A, Kimoto T, Chikura S, Miura D, Itoh S, Muto S, Uno Y, Sanada H, Takashima R, Shigano M, Takasawa H, Hamada S, Yamamoto M, Hori H, Tsutsumi E, Wada K, Maeda A, Kikuzuki R, Ogiwara Y, Kyoya T, Adachi H, Uematsu Y, Yoshida I, Narumi K, Fujiishi Y, Fukuda T, Suzuki Y, Goto K, Morita T, Honma M
    • Organizer
      Environmental Mutagen Society 46th Annual Meeting
    • Place of Presentation
      New Orleans, Louisiana, USA
    • Year and Date
      2015-09-26
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 共同研究報告I:Pig-a アッセイ2015

    • Author(s)
      堀端克良
    • Organizer
      哺乳動物試験研究会第66回定例会
    • Place of Presentation
      栃木
    • Year and Date
      2015-06-12
    • Related Report
      2015 Research-status Report
  • [Presentation] Pig-a/PIGRETアッセイに関する短期試験への有用性:MMS共同研究報告2014

    • Author(s)
      山田雅巳, 堀端克良, 鵜飼明子, 木本崇文, 千藏さつき, 伊東悟, 武藤重治, 宇野芳文, 真田尚和, 高島理恵,志賀野美幸,高沢博修, 濵田修一,山本美佳, 堀妃佐子, 堤絵梨, 和田邦生, 前田晃央, 小坂瑞樹, 木村葵, 菊月隆太, 荻原庸介, 京谷恭弘, 足立秀樹, 上松泰明, 吉田唯真, 成見香瑞範, 福田隆之, 鈴木裕太, 後藤玄, 森田健, 本間正充
    • 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] MMS/Pig-a共同研究:アクリルアミドの遺伝毒性評価2014

    • Author(s)
      堀端克良,鵜飼明子,本間正充
    • 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] 共同研究報告I:Pig-a assay 進捗状況報告2014

    • Author(s)
      堀端克良
    • Organizer
      哺乳動物試験研究会第65回定例会
    • Place of Presentation
      東京
    • Year and Date
      2014-12-03
    • Related Report
      2014 Research-status Report
  • [Presentation] マウス、ラットおよびヒト由来のごく微量末梢血を用いて解析可能なPig-a/ PIG-A in vivo突然変異試験法2014

    • Author(s)
      堀端克良,鵜飼明子,石川恵生,菅野絢子,木本崇文,本間正充
    • Organizer
      第37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 Research-status Report
  • [Presentation] ESTABLISHMENT OF HUMAN PIG-A ASSAY AND APPLICATION TO GENOTOXICITY MONITORING OF CANCER CHEMOTHERAPEUTIC PATIENTS2014

    • Author(s)
      K. Horibata, M. Honma
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 共同研究報告 I:Pig-a assay 進捗状況報告2014

    • Author(s)
      堀端克良
    • Organizer
      哺乳動物試験研究会第64回定例会
    • Place of Presentation
      熱海
    • Year and Date
      2014-06-20 – 2014-06-21
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2023-03-23  

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