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Mechanism analysis of progressive neurological abnormalities in xeroderma pigmentosum group A patients

Research Project

Project/Area Number 26550042
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Risk sciences of radiation and chemicals
Research InstitutionNara Medical University

Principal Investigator

Mori Toshio  奈良県立医科大学, 医学部, 研究教授 (10115280)

Research Collaborator Brooks P. J.  
Nakane Hironobu  
Hayashi Masaharu  
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords色素性乾皮症 / 神経障害 / 酸化的DNA損傷 / サイクロプリン / モノクローナル抗体 / DNA修復異常 / 活性酸素 / ヌクレオチド除去修復 / 酵素標識免疫法
Outline of Final Research Achievements

Xeroderma pigmentosum group A (XP-A) patients develop progressive neurological abnormalities, which has been hypothesized to be associated with a type of oxidatively generated DNA damage called purine 8,5’-cyclo-2’-deoxynucleosides. Thus, we generated a monoclonal antibody specific for 8,5’-cyclo-2’-deoxynadenosine (Cyclo-dA) in DNA. The immunoassay revealed a linear dose-response between known amounts of Cyclo-dA in oligonucleotides and the antibody binding to them with a detection sensitivity of about 1 lesion/10<6> bases in a 1 ug DNA sample. We compared the amounts of Cyclo-dA accumulated in organs between wild type and XP-A mice with ages from 5 months to 29 months. We found that XP-A mice accumulate significantly higher amounts of Cyclo-dA in brains than do wild type mice, supporting the hypothesis.

Report

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

    (17 results)

All 2017 2016 2015 2014 Other

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Targeted Inactivation of DNA Photolyase Genes in Medaka Fish (Oryzias latipes)2017

    • Author(s)
      Ishikawa-Fujiwara T, Shiraishi E, Fujikawa Y, Mori T, Tsujimura T, Todo T
    • Journal Title

      Photochemistry and Photobiology

      Volume: 93 Issue: 1 Pages: 315-322

    • DOI

      10.1111/php.12658

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Radiation-induced RhoGDIβ cleavage leads to perturbation of cell polarity: a possible link to cancer spreading2016

    • Author(s)
      Fujiwara, M., Okamoto, M., Hori, M., Suga, H., Jikihara, H., Sugihara, Y., Shimamoto, F., Mori, T., Nakaoji, K., Hamada, K., Ota, T., Wiedemuth, R., Temme, A., and Tatsuka, M.
    • Journal Title

      J Cell Physiol

      Volume: 0 Issue: 11 Pages: 0-0

    • DOI

      10.1002/jcp.25362

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] In vivo spectrum of UVC-induced mutation in mouse skin epidermis may reflect the cytosine deamination propensity of cyclobutane pyrimidine dimers.2015

    • Author(s)
      H. Ikehata, T. Mori and M. Yamamoto
    • Journal Title

      Photochem. Photobiol.

      Volume: 91 Issue: 6 Pages: 1488-1496

    • DOI

      10.1111/php.12525

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / 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] Functional regulation of the DNA damage-recognition factor DDB2 by ubiquitination and interaction with xeroderma pigmentosum group C protein.2015

    • Author(s)
      Syota Matsumoto, Eric S. Fischer, Takeshi Yasuda, Naoshi Dohmae, Shigenori Iwai, Toshio Mori, Ryotaro Nishi, Ken-ichi Yoshino, Wataru Sakai, Fumio Hanaoka, Nicolas H. Thoma, Kaoru Sugasawa
    • Journal Title

      Nucleic Acids Research

      Volume: 3 Issue: 3 Pages: 1700-1713

    • DOI

      10.1093/nar/gkv038

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantitative and in situ detection of oxidatively generated DNA damage 8,5’-cyclo-2’-deoxyadenosine using an immunoassay with a novel monoclonal antibody2014

    • Author(s)
      T. Iwamoto, P.J. Brooks, T. Nishiwaki, K. Nishimura, N. Kobayashi, S. Sugiura and T. Mori.
    • Journal Title

      Photochem. Photobiol.

      Volume: xx Issue: 4 Pages: 829-836

    • DOI

      10.1111/php.12239

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 紫外線および酸化的DNA損傷に対するモノクローナル抗体の作製と応用2017

    • Author(s)
      森 俊雄
    • Organizer
      太陽紫外線防御研究員会第27回シンポジウム
    • Place of Presentation
      大阪
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 紫外線誘発DNA損傷に対するモノクローナル抗体2016

    • Author(s)
      森 俊雄
    • Organizer
      日本放射線影響学会第59回大会
    • Place of Presentation
      広島
    • Year and Date
      2016-10-26
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 酸化的DNA損傷サイクロプリン定量系の高感度化2016

    • Author(s)
      森 俊雄、岩本顕聡、杉浦重樹、中根裕信
    • Organizer
      第38回日本光医学・光生物学会
    • Place of Presentation
      京都
    • Year and Date
      2016-07-22
    • Related Report
      2016 Annual Research Report
  • [Presentation] DNA修復異常疾患(XP/CS/TTD)の病態と細胞/分子レベルの特性との関連2015

    • Author(s)
      森 俊雄
    • Organizer
      第37回日本光医学・光生物学会
    • Place of Presentation
      宮崎
    • Year and Date
      2015-07-17
    • Related Report
      2015 Research-status Report
  • [Presentation] Quantitative detection of oxidative DNA damage 8,5’-cyclo-2’-deoxyadenosine using an immunoassay with a novel monoclonal antibody2015

    • Author(s)
      T. Mori, T. Iwamoto, P. J. Brooks, N. Kobayashi and S. Sugiura
    • Organizer
      15th International Congress of Radiation Research
    • Place of Presentation
      Kyoto
    • Year and Date
      2015-05-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 新規モノクローナル抗体を用いた酸化的DNA損傷サイクロプリンの定量測定と可視化2014

    • Author(s)
      森 俊雄、岩本顕聡、小林信彦、杉浦重樹
    • 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] Quantitative and in situ detection of oxidatively generated DNA damage 8,5’-cyclo-2’-deoxyadenosine using an immunoassay with a novel monoclonal antibody2014

    • Author(s)
      T. Iwamoto, P.J. Brooks, N. Kobayashi, S. Sugiura and T. Mori
    • Organizer
      16th International Congress on Photobiology
    • Place of Presentation
      Cordoba, Argentina
    • Year and Date
      2014-09-08 – 2014-09-12
    • Related Report
      2014 Research-status Report
  • [Presentation] 新規モノクローナル抗体を用いた酸化的DNA損傷サイクロプリンの定量測定と可視化2014

    • Author(s)
      岩本顕聡、P.J. Brooks、小林信彦、杉浦重樹、森 俊雄
    • Organizer
      第36回日本光医学・光生物学会
    • Place of Presentation
      大阪
    • Year and Date
      2014-07-25 – 2014-07-26
    • Related Report
      2014 Research-status Report
  • [Book] 4.2 ヒトにおけるヌクレオチド除去修復のしくみ、放射線医科学 -生体と放射線・電磁波・超音波-2016

    • Author(s)
      森 俊雄
    • Total Pages
      189
    • Publisher
      医療科学社
    • Related Report
      2016 Annual Research Report
  • [Book] 光老化科学の最前線、第10章 DNA損傷の定量測定と可視化2015

    • Author(s)
      森 俊雄 (前田憲寿監修)
    • Total Pages
      301
    • Publisher
      シーエムシー出版
    • Related Report
      2015 Research-status Report
  • [Remarks] 奈良県立医科大学ラジオアイソトープ(RI)実験施設

    • URL

      http://www.naramed-u.ac.jp/university/kenkyu-sangakukan/radioisotope/radioisotope.html

    • Related Report
      2014 Research-status Report

URL: 

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

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