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Functional analyses of translesion synthesis DNA polymerase Poleta based on its structural features

Research Project

Project/Area Number 26340028
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Risk sciences of radiation and chemicals
Research InstitutionKobe University (2016-2017)
Gakushuin University (2014-2015)

Principal Investigator

YOKOI MASAYUKI  神戸大学, バイオシグナル総合研究センター, 准教授 (00322701)

Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords損傷乗り越え合成 / DNA損傷 / TLSポリメラーゼ / 阻害剤 / 損傷乗り越え複製 / Polη / 紫外線
Outline of Final Research Achievements

Human Poleta is a major translesion synthesis polymerase involved in DNA damage tolerance against UV- or cisplatin-induced DNA lesions. To elucidate its physiological function and regulatory mechanism in cellular DNA damage tolerance, I focused on unique structural features of human Poleta identified from the comparison of its crystal structure against other eukaryotic TLS polymerases. As a result, unique amino acid sequences or amino acid residues of human Poleta were deleted or substituted by other amino acid to investigate their role. Biochemical and cellular analyses using these mutant proteins revealed that some of them were important for the translesion synthesis activity or regulation of human Poleta. It was notable, in this research, that several novel proteins and chemical compounds were identified to interact with or regulate human Poleta. These findings will open new phase of research on DNA damage tolerance associated with human Poleta.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (16 results)

All 2017 2016 2015 2014 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results,  Acknowledgement Compliant: 3 results) Presentation (12 results) (of which Invited: 1 results) Remarks (1 results)

  • [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] 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
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Remarkable induction of UV-signature mutations at the 3'-cytosine of dipyrimidine sites except at 5'-TCG-3' in the UVB-exposed skin epidermis of xeroderma pigmentosum variant model mice.2014

    • Author(s)
      Ikehata H, Chang Y, Yokoi M, Yamamoto M, Hanaoka F
    • Journal Title

      DNA Repair

      Volume: 22 Pages: 112-122

    • DOI

      10.1016/j.dnarep.2014.07.012

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 損傷乗り越え型DNAポリメラーゼ イータ・イオタ・カッパ三重欠損細胞を用いた新規遺伝毒性試験法の研究2017

    • Author(s)
      赤木純一、横井雅幸、Young-Man Cho、豊田武士、大森治夫、花岡文雄、小川久美子
    • Organizer
      第3回 次世代を担う若手のためのレギュラトリーサイエンスフォーラム
    • Related Report
      2017 Annual Research Report
  • [Presentation] Chromatin remodeling factors contribute to the function of human DNA polymerase η in the cells treated with cisplatin2017

    • Author(s)
      Yokoi, M., Sugasawa, K., Hanaoka, F.
    • Organizer
      第76回 日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Functional analysis of human DNA polymerase η harboring mutations in the palm domain2016

    • Author(s)
      Yokoi, M., Mishima, K., Noda, C., Nishimura, J., Yang, W., Hanaoka, F.
    • Organizer
      第39回 日本分子生物学会
    • Place of Presentation
      神奈川県横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] Structure and function relations of human DNA polymerase η: mutations of the finger or little finger domains alter lesion bypass efficiencies2016

    • Author(s)
      Yokoi, M., Onaka, S., Mishima, K., Yang, W., Hanaoka, F.
    • Organizer
      The 10th 3R Symposium
    • Place of Presentation
      島根県松江市
    • Year and Date
      2016-11-13
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒトPolηの構造的特徴と損傷乗り越え活性の連関2016

    • Author(s)
      横井雅幸
    • Organizer
      生物ゲノム安定維持の分子機構
    • Place of Presentation
      国立遺伝学研究所
    • Year and Date
      2016-10-24
    • Related Report
      2016 Research-status Report
  • [Presentation] Unidentified function of DNA polymerase η and ι in cellular sensitivity to an oxidizing agent potassium bromate2015

    • Author(s)
      Dotsu, K., Ohkumo, T., Yokoi, M., and Hanaoka, F.
    • Organizer
      第38回 日本分子生物学会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Mutations of the finger or little-finger domains in human Polη alter lesion bypass efficiencies when copying DNA containing cyclobutane pyrimidine dimer2015

    • Author(s)
      Yokoi, M., Onaka, S., Mishima, K., Hanaoka, F.
    • Organizer
      第38回 日本分子生物学会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Hypersensitivity of Pols η, ι, and κ triple knockout cells to mutagens is a valuable indicator of genotoxicity2015

    • Author(s)
      150.Akagi, J., Yokoi, M., Cho, Y-M., Toyoda, T., Hanaoka, F., Ogawa, K
    • Organizer
      第74回 日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] High concentration of dATP attenuated the catalytic rate and efficiency of translesion2015

    • Author(s)
      Yokoi, M., and Hanaoka, F.
    • Organizer
      第74回 日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Roles of DNA polymerase η and ι in UV-induced mutagenesis of skin cells and tissues2015

    • Author(s)
      149.Sakurai, Y., Yokoi, M., Tsukamoto, T., Wei, M., Wanibuchi, H., Murakumo, Y., Hanaoka, F.
    • Organizer
      第104回 日本病理学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2015-04-30
    • Related Report
      2015 Research-status Report
  • [Presentation] Roles of mammalian DNA polymerase η and ι UV-induced mutagenesis.2014

    • Author(s)
      Hanaoka, F., Sakurai, Y.,Yokoi, M.
    • Organizer
      3R Symposium
    • Place of Presentation
      御殿場
    • Year and Date
      2014-11-18
    • Related Report
      2014 Research-status Report
  • [Presentation] アミノ酸置換変異体を用いたヒトPolηの機能解析2014

    • Author(s)
      横井雅幸
    • Organizer
      国立遺伝学研究所研究集会
    • Place of Presentation
      三島
    • Year and Date
      2014-11-07
    • Related Report
      2014 Research-status Report
    • Invited
  • [Remarks] 学習院大学 花岡研究室

    • URL

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

    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2019-03-29  

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