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Novel molecular mechanism maintaining genomic homeostasis against environmental stresses

Research Project

Project/Area Number 24241019
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Risk sciences of radiation/Chemicals
Research InstitutionKobe University

Principal Investigator

SUGASAWA Kaoru  神戸大学, 自然科学系先端融合研究環バイオシグナル研究センター, 教授 (70202124)

Co-Investigator(Kenkyū-buntansha) IWAI Shigenori  大阪大学, 基礎工学研究科, 教授 (10168544)
Co-Investigator(Renkei-kenkyūsha) YOKOTA Hiroaki  光産業創成大学院大学, 光産業創成研究科, 准教授 (90415547)
YOSHINO Ken-ichi  神戸大学, 自然科学系先端融合研究環バイオシグナル研究センター, 助教 (90280792)
Research Collaborator AKITA Masaki  
MATSUMOTO Syota  
TONE Daisuke  
ONISHI Yuki  
KINOSHITA Minoru  
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥43,030,000 (Direct Cost: ¥33,100,000、Indirect Cost: ¥9,930,000)
Fiscal Year 2014: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2013: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
Fiscal Year 2012: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Keywords遺伝子 / ゲノム / 蛋白質 / DNA損傷修復 / 一分子解析
Outline of Final Research Achievements

This research project was aimed to understand the molecular bases, which enable the global genomic nucleotide excision repair (GG-NER) pathway to efficiently survey genomic DNA for damage caused by various environmental stresses. By using the defined cell-free GG-NER system reconstituted with purified recombinant protein factors, it was shown that certain endogenous DNA lesions, such as abasic sites, facilitate the damage recognition process in GG-NER, and that DNA repair efficiency is affected by the topological state of damaged DNA as well as protein phosphorylation. We also elucidated novel roles of ubiquitination and SUMOylation of the xeroderma pigmentosum group C (XPC) protein in recognition of ultraviolet (UV)-induced DNA photolesions mediated by the UV-damaged DNA binding protein complex. Finally, single molecule imaging experiments revealed one-dimensional diffusion of the XPC protein during the search for lesions along DNA.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (32 results)

All 2015 2014 2013 2012 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (20 results) (of which Invited: 3 results) Remarks (3 results)

  • [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
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fluorescence detection of cellular nucleotide excision repair of damaged DNA.2014

    • Author(s)
      Toga, T., Kuraoka, I., Watanabe, S., Nakano, E., Takeuchi, S., Nishigori, C., Sugasawa, K. and Iwai, S.
    • Journal Title

      Scientific Reports

      Volume: 4 Issue: 1 Pages: 5578-5578

    • DOI

      10.1038/srep05578

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PRDM14 promotes active DNA demethylation through the Ten-eleven translocation (TET)-mediated base excision repair pathway in embryonic stem cells.2014

    • Author(s)
      Okashita, N., Kumaki, Y., Ebi, K., Nishi, M., Okamoto, Y., Nakayama, M., Hashimoto, S., Nakamura, T., Sugasawa, K., Kojima, N., Takada, T., Okano, M. and Seki, Y.
    • Journal Title

      Development

      Volume: 141 Issue: 2 Pages: 269-280

    • DOI

      10.1242/dev.099622

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparative analysis of interaction of human and yeast DNA damage recognition complexes with damaged DNA in nucleotide excision repair.2013

    • Author(s)
      Krasikova, Y. S., Rechkunova, N. I., Maltseva, E. A., Pestryakov, P. E., Petruseva, I. O., Sugasawa, K., Chen, X., Min, J. H. and Lavrik, O. I.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 288 Issue: 15 Pages: 10936-10947

    • DOI

      10.1074/jbc.m112.444026

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure-function analysis of the EF-hand protein centrin-2 for its intracellular localization and nucleotide excision repair.2013

    • Author(s)
      Nishi R, Sakai W, Tone D, Hanaoka F, Sugasawa K
    • Journal Title

      Nucleic Acids Res

      Volume: 41 Issue: 14 Pages: 6917-6929

    • DOI

      10.1093/nar/gkt434

    • NAID

      120005621886

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Structure-specific endonucleases Xpf and Mus81 play overlapping but essential roles in DNA repair by homologous recombination.2013

    • Author(s)
      Kikuchi K, Narita T, Pham 〓, Iij〓 J, Hirota K, Islam SK, Mohiuddin M, Okawa K, Bori T, Fukagama T, Essers J, Kanser R, Whithy NC, Sugasawa K, Taniguchi T, Kitagawa K. Takeda S.
    • Journal Title

      Cancer Res.

      Volume: (in press) Issue: 14 Pages: 6917-6929

    • DOI

      10.1158/0008-5472.can-12-3154

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human and yeast DNA damage recognition complexes bind with high affinity DNA structures mimicking in size transcription bubble.2013

    • Author(s)
      Krasikova, Y. S., Rechkunova, N. I., Maltseva, E. A., Anarbaev, R. O., Pestryakov, P. E., Sugasawa, K., Min, J. H. and Lavrik, O. I.
    • Journal Title

      Journal of Molecular Recognition

      Volume: 26 Issue: 12 Pages: 653-661

    • DOI

      10.1002/jmr.2308

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC12012

    • Author(s)
      Pines, A. et al.
    • Journal Title

      J. Cell. Biol.

      Volume: 199 Issue: 2 Pages: 235-249

    • DOI

      10.1083/jcb.201112132

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Two different RFC proteins, Ctf18 and RFC1 separately control PCNA-CRL4Cdt2-mediated Cdt1 proteolysis during S phase and following UV-irradiation2012

    • Author(s)
      Shiomi Y, Ishii T, Hayashi A, Shinmyozu K, Nakayama J, Sugasawa K, & Nishitani H
    • Journal Title

      Mol Cell Biol

      Volume: 32 Issue: 12 Pages: 2279-88

    • DOI

      10.1128/mcb.06506-11

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] In vivo regulation of mammalian nucleotide excision repair.2015

    • Author(s)
      Sugasawa, K.
    • Organizer
      Gordon Research Conference on Mammalian DNA Repair
    • Place of Presentation
      Four Points Sheraton, Ventura, CA, U.S.A.
    • Year and Date
      2015-02-08 – 2015-02-14
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 哺乳類ヌクレオチド除去修復タンパク質XPCのDNA結合モードの1分子イメージング2014

    • Author(s)
      横田浩章、戸根大輔、大西優貴、韓 龍雲、原田慶恵、菅澤 薫
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] ヌクレオチド除去修復におけるDNA損傷認識機構の解析2014

    • Author(s)
      大西優貴、戸根大輔、木下 実、岩井成憲、菅澤 薫
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] DNA損傷応答におけるDDB2の翻訳後修飾の機能解析2014

    • Author(s)
      松本翔太、Eric S. Fischer、Nicolas H. Thoma、菅澤 薫
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Functional interactions between XPC and DDB2 in nucleotide excision repair2014

    • Author(s)
      Matsumoto, S., Fischer, E. S., Thoma, N. H. and Sugasawa, K.
    • Organizer
      The 9th 3R Symposium
    • Place of Presentation
      御殿場高原ホテル
    • Year and Date
      2014-11-17 – 2014-11-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] ヌクレオチド除去修復におけるXPCとDDB2の機能的相互作用2014

    • Author(s)
      松本翔太、Eric S. Fischer、Nicolas H. Thoma、菅澤 薫
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 紫外線誘発DNA損傷修復の細胞内制御機構2014

    • Author(s)
      菅澤 薫
    • Organizer
      日本放射線影響学会第57回大会
    • Place of Presentation
      かごしま県民交流センター
    • Year and Date
      2014-10-01 – 2014-10-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] Roles for post-translational protein modifications in regulation of DNA damage recognition for mammalian nucleotide excision repair.2014

    • Author(s)
      Akita, M., Matsumoto, S., Sakai, W. and Sugasawa, K.
    • Organizer
      International Symposium on Xeroderma Pigmentosum and Related Diseases
    • Place of Presentation
      神戸国際会議場
    • Related Report
      2013 Annual Research Report
  • [Presentation] ゲノムDNA損傷の修復と細胞応答を制御するタンパク質翻訳後修飾の役割2013

    • Author(s)
      菅澤 薫
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] 紫外線誘発DNA損傷の修復機構におけるSUMO化修飾の役割2013

    • Author(s)
      秋田眞季、酒井 恒、菅澤 薫
    • Organizer
      日本放射線影響学会第56回大会
    • Place of Presentation
      ホテルクラウンパレス青森
    • Related Report
      2013 Annual Research Report
  • [Presentation] 哺乳類ヌクレオチド除去修復タンパク質XPCの1分子イメージング2013

    • Author(s)
      横田浩章、西幹栄美、戸根大輔、韓 龍雲、原田慶恵、菅澤 薫
    • Organizer
      第51回日本生物物理学会年会
    • Place of Presentation
      国立京都国際会館
    • Related Report
      2013 Annual Research Report
  • [Presentation] ヌクレオチド除去修復における損傷認識機構とSUMO化修飾の意義2013

    • Author(s)
      秋田眞季、松本翔太、菅澤 薫
    • Organizer
      第22回DNA複製・組換え・修復ワークショップ
    • Place of Presentation
      ホテルニュー水戸屋(仙台)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 哺乳類ヌクレオチド除去修復におけるDNA損傷認識課程の制御2013

    • Author(s)
      菅澤 薫
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2013 Annual Research Report
  • [Presentation] 哺乳類ヌクレオチド除去修復タンパク質XPCの1分子イメージング:DNA上での1次元自由拡散運動の観察2013

    • Author(s)
      横田浩章、戸根大輔、韓 龍雲、原田慶恵、菅澤 薫
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2013 Annual Research Report
  • [Presentation] Post-translational protein modification regulating mammalian nucleotide excision repair2012

    • Author(s)
      Sugasawa, K.
    • Organizer
      The 4th US-Japan DNA Repair Meeting
    • Place of Presentation
      Leesburg, VA, USA
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 紫外線誘発DNA損傷の認識と修復の分子基盤2012

    • Author(s)
      菅澤 薫
    • Organizer
      第34回日本光医学・光生物学会
    • Place of Presentation
      神戸
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 紫外線によるDNA損傷の修復を促進するDDB2の構造と機能制御2012

    • Author(s)
      松本翔太 他
    • Organizer
      日本放射線影響学会第55回大会
    • Place of Presentation
      仙台
    • Related Report
      2012 Annual Research Report
  • [Presentation] Functional regulation of the DNA damage recognition factor DDB2 via post- translational modifications2012

    • Author(s)
      Sugasawa, K. and Hanaoka, F.
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Annual Research Report
  • [Presentation] A novel function of centrin-2 involved in maintenance of genomic stability2012

    • Author(s)
      Sugasawa, K. et al.
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] Exploration of novel regulatory factors in mammalian nucleotide excision repair2012

    • Author(s)
      Tone, D. et al.
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Remarks] 神戸大学バイオシグナル研究センター 菅澤研究室

    • URL

      http://www.research.kobe-u.ac.jp/brce-sugasawa/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 神戸大学バイオシグナル研究センター 菅澤研究室

    • URL

      http://www.research.kobe-u.ac.jp/brce-sugasawa/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 神戸大学バイオシグナル研究センター 菅澤研究室

    • URL

      http://www.research.kobe-u.ac.jp/brce-sugasawa/

    • Related Report
      2012 Annual Research Report

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Published: 2013-05-15   Modified: 2019-07-29  

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