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Analysis and regulation of cellular function of topologies of nucleic acid quadruplex.

Research Project

Project/Area Number 17K01968
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Chemical biology
Research InstitutionKonan University

Principal Investigator

Takahashi Shuntaro  甲南大学, 先端生命工学研究所, 准教授 (40456257)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
KeywordsDNA / 四重鎖構造 / トポロジー / DNA複製 / 分子環境 / 細胞内環境 / 熱力学解析 / 分子クラウディング / フーグスティーン塩基対 / 構造安定性予測 / リガンド / i-motif / 酸化ストレス / グアニン四重鎖 / 人工核酸 / 熱力学 / 動力学 / i-motif構造 / 複製 / 四重鎖
Outline of Final Research Achievements

In this study, we aimed to quantitatively analyze the effects of topological changes in DNA quadruplex structures on gene replication reactions and to elucidate their intracellular functions. For this purpose, we developed a correlation analysis method between the energy value of the nucleic acid structure and the replication rate, and quantitatively analyzed the gene replication control mechanism involving the nucleic acid topology. It was found that the replication inhibition effect was different depending on the quadruplex topology. Furthermore, by using pyrene-modifieded artificial nucleic acids, we succeeded in changing the topology of the G-quadruplex of the oxidatively damaged VEGF gene and restored the regulatory function of the replication reaction that was impaired by oxidative damage.

Academic Significance and Societal Importance of the Research Achievements

本研究で明らかにしたトポロジー依存的な遺伝子制御は、遺伝子配列の変化が伴わないことが特徴である。つまり、生命は核酸構造の化学環境に対する多様な応答性を利用し、遺伝子発現を高次化することで、高度な生命現象を獲得してきたと考えられる。例えば、細胞分化・発生などの塩基配列の変異を伴わずに細胞の状態が変化する過程において、このトポロジー制御が重要な役割を果たしている可能性がある。また、このようなシステムが破綻することによって、癌、神経疾患、生活習慣病などの後天的な疾患が引き起こされると考えられる。本研究のさらなる発展により、医療、診断、創薬などの実社会に貢献する様々な分野への研究展開が期待される。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (54 results)

All 2021 2020 2019 2018 2017 Other

All Int'l Joint Research (9 results) Journal Article (25 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 21 results,  Open Access: 11 results) Presentation (17 results) (of which Int'l Joint Research: 6 results,  Invited: 2 results) Book (1 results) Remarks (2 results)

  • [Int'l Joint Research] KU Leuven(ベルギー)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] University of Calcutta(インド)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Carnegie Mellon University(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Culcatta大学(インド)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] University of Calcutta(インド)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] POSTECH(韓国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] The Russian Academy of Sciences(ロシア連邦)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Slovenian NMR Center(スロベニア)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] University of Reading(英国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Watson-Crick versus Hoogsteen Base Pairs: Chemical Strategy to Encode and Express Genetic Information in Life2021

    • Author(s)
      Takahashi Shuntaro、Sugimoto Naoki
    • Journal Title

      Accounts of Chemical Research

      Volume: 54 Issue: 9 Pages: 2110-2120

    • DOI

      10.1021/acs.accounts.0c00734

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Engineering exosome polymer hybrids by atom transfer radical polymerization2021

    • Author(s)
      S. Lathwal, S. S. Yerneni, S. Boye, U. L. Muza, S. Takahashi, N. Sugimoto, A. Lederer, S. R. Das, P. G. Campbell, and K. Matyjaszewski
    • Journal Title

      Proc. Natl. Acad. Sci. U. S. A.

      Volume: 118 Issue: 2

    • DOI

      10.1073/pnas.2020241118

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Stability prediction of canonical and non-canonical structures of nucleic acids in various molecular environments and cells2020

    • Author(s)
      S. Takahashi and N. Sugimoto
    • Journal Title

      Chem. Soc. Rev.

      Volume: 49 Issue: 23 Pages: 8439-8468

    • DOI

      10.1039/d0cs00594k

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of Molecular Crowding on DNA Polymerase Reactions along Unnatural DNA Templates2020

    • Author(s)
      S. Takahashi, P. Herdwijn, and N. Sugimoto
    • Journal Title

      Molecules

      Volume: 25 Issue: 18 Pages: 4120-4120

    • DOI

      10.3390/molecules25184120

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular crowding induces primer extension by RNA polymerase through base stacking beyond Watson-Crick rules2020

    • Author(s)
      S. Takahashi, H. Okura, P. Chilika, S. Ghosh, and N. Sugimoto
    • Journal Title

      RSC Adv.

      Volume: 10 Issue: 55 Pages: 33052-33058

    • DOI

      10.1039/d0ra06502a

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nearest-neighbor parameters for predicting DNA duplex stability in diverse molecular crowding conditions2020

    • Author(s)
      S. Ghosh, S. Takahashi, T. Ohyama, T. Endoh, H. Tateishi-Karimata, and N. Sugimoto
    • Journal Title

      Proc. Natl. Acad. Sci. USA.

      Volume: 117 Issue: 25 Pages: 14194-14201

    • DOI

      10.1073/pnas.1920886117

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of morecular crowding on the stability of RNA G-quadruplexes with various numbers of quartets and lengths of loops2020

    • Author(s)
      S. Matsumoto, H. Tateishi-Karimata, S. Takahashi, T. Ohyama, and N. Sugimoto
    • Journal Title

      Biochemistry

      Volume: 59 Issue: 28 Pages: 2640-2649

    • DOI

      10.1021/acs.biochem.0c00346

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Improved nearest-neighbor parameters for the stability of RNA/DNA hybrids under a physiological condition2020

    • Author(s)
      D. Banerjee, H. Tateishi-Karimata, T. Ohyama, S. Ghosh, T. Endoh, S. Takahashi, and N. Sugimoto
    • Journal Title

      Nucleic Acids Res.

      Volume: 48 Issue: 21 Pages: 12042-12054

    • DOI

      10.1093/nar/gkaa572

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 高圧力が生物関連成分に及ぼす影響-1 高圧力がDNAに及ぼす影響 非標準構造と分子クラウディングの視点2020

    • Author(s)
      高橋俊太郎、杉本直己
    • Journal Title

      化学と生物

      Volume: 58 Pages: 477-485

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 核酸構造のトポロジーを基盤とする遺伝子発現の化学的制御 非二重らせんの構造と機能に関する新概念2020

    • Author(s)
      高橋俊太郎
    • Journal Title

      化学と工業

      Volume: 73 Pages: 644-645

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Thrombin binding aptamer G-quadruplex stabilized by pyrene-modified nucleotides2020

    • Author(s)
      Kovacic Matic、Podbevsek Peter、Tateishi-Karimata Hisae、Takahashi Shuntaro、Sugimoto Naoki、Plavec Janez
    • Journal Title

      Nucleic Acids Research

      Volume: 48 Issue: 7 Pages: 3975-3986

    • DOI

      10.1093/nar/gkaa118

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Preferential targeting cancer-related i-motif DNAs by the plant flavonol fisetin for theranostics applications2020

    • Author(s)
      Takahashi Shuntaro、Bhattacharjee Snehasish、Ghosh Saptarshi、Sugimoto Naoki、Bhowmik Sudipta
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 2504-2504

    • DOI

      10.1038/s41598-020-59343-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 平成の化学キーワード 核酸の多様性を生みだすもう一つの塩基対相互作用 フーグスティーン塩基対2019

    • Author(s)
      高橋俊太郎、杉本直己
    • Journal Title

      化学(化学同人)

      Volume: 74 Pages: 24-25

    • Related Report
      2019 Research-status Report
  • [Journal Article] Quantitative Analysis of Stall of Replicating DNA Polymerase by G-Quadruplex Formation2019

    • Author(s)
      Takahashi Shuntaro、Sugimoto Naoki
    • Journal Title

      Methods in Molecular Biology

      Volume: 2035 Pages: 257-274

    • DOI

      10.1007/978-1-4939-9666-7_15

    • ISBN
      9781493996650, 9781493996667
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 分子夾雑系の生命化学(2)-遺伝子発現のデジタル挙動とアナログ挙動-2019

    • Author(s)
      高橋俊太郎, 杉本直己
    • Journal Title

      現代化学(化学同人)

      Volume: 575 Pages: 34-38

    • Related Report
      2018 Research-status Report
  • [Journal Article] Bisubstrate Function of RNA Polymerases Triggered by Molecular Crowding Conditions2019

    • Author(s)
      Takahashi Shuntaro、Okura Hiromichi、Sugimoto Naoki
    • Journal Title

      Biochemistry

      Volume: 58 Issue: 8 Pages: 1081-1093

    • DOI

      10.1021/acs.biochem.8b01204

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lighting Up of Thiazole Orange on G-Quadruplex DNA by High Pressure2019

    • Author(s)
      Bhowmik Sudipta、Takahashi Shuntaro、Sugimoto Naoki
    • Journal Title

      ACS Omega

      Volume: 4 Issue: 2 Pages: 4325-4329

    • DOI

      10.1021/acsomega.8b03430

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Characterization of Intracellular Crowding Environments with Topology-Based DNA Quadruplex Sensors2019

    • Author(s)
      Takahashi Shuntaro、Yamamoto Johtaro、Kitamura Akira、Kinjo Masataka、Sugimoto Naoki
    • Journal Title

      Analytical Chemistry

      Volume: 91 Issue: 4 Pages: 2586-2590

    • DOI

      10.1021/acs.analchem.8b04177

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Design and Properties of Ligand-Conjugated Guanine Oligonucleotides for Recovery of Mutated G-Quadruplexes2018

    • Author(s)
      Takahashi Shuntaro、Chelobanov Boris、Kim Ki、Kim Byeang、Stetsenko Dmitry、Sugimoto Naoki
    • Journal Title

      Molecules

      Volume: 23 Issue: 12 Pages: 3228-3228

    • DOI

      10.3390/molecules23123228

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Recovery of the Formation and Function of Oxidized G-Quadruplexes by a Pyrene-Modified Guanine Tract2018

    • Author(s)
      Takahashi Shuntaro、Kim Ki Tae、Podbevsek Peter、Plavec Janez、Kim Byeang Hyean、Sugimoto Naoki
    • Journal Title

      Journal of the American Chemical Society

      Volume: 140 Issue: 17 Pages: 5774-5783

    • DOI

      10.1021/jacs.8b01577

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Alkylating probes for the G-quadruplex structure and evaluation of the properties of the alkylated G-quadruplex DNA2018

    • Author(s)
      Sato Norihiro、Takahashi Shuntaro、Tateishi-Karimata Hisae、Hazemi Madoka E.、Chikuni Tomoko、Onizuka Kazumitsu、Sugimoto Naoki、Nagatsugi Fumi
    • Journal Title

      Org. Biomol. Chem.

      Volume: 16 Issue: 9 Pages: 1436-1441

    • DOI

      10.1039/c7ob03179c

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Topological impact of noncanonical DNA structures on Klenow fragment of DNA polymerase2017

    • Author(s)
      Takahashi Shuntaro、Brazier John A.、Sugimoto Naoki
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 114 Issue: 36 Pages: 9605-9610

    • DOI

      10.1073/pnas.1704258114

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Volumetric contributions of loop regions of G-quadruplex DNA to the formation of the tertiary structure2017

    • Author(s)
      Takahashi Shuntaro、Sugimoto Naoki
    • Journal Title

      Biophysical Chemistry

      Volume: 231 Pages: 146-154

    • DOI

      10.1016/j.bpc.2017.02.001

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Quantitative Analysis of Nucleic Acid Stability with Ligands Under High Pressure to Design Novel Drugs Targeting G-Quadruplexes2017

    • Author(s)
      Takahashi Shuntaro、Sugimoto Naoki
    • Journal Title

      Current Protocols in Nucleic Acid Chemistry

      Volume: 70 Issue: 1

    • DOI

      10.1002/cpnc.39

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 分子クラウディングワールド―クラウディングによる疾患や分子進化の化学的制御2017

    • Author(s)
      高橋俊太郎、杉本直己
    • Journal Title

      化学(化学同人)

      Volume: 7 Pages: 12-17

    • NAID

      40021242573

    • Related Report
      2017 Research-status Report
  • [Presentation] Nucleic Acid Chemistry beyond Watson-Crick Double Helix (71): I-motif stability prediction under molecular crowding conditions2021

    • Author(s)
      Pallavi Chilka, Shuntaro Takahashi, Naoki Sugimoto
    • Organizer
      日本化学会第101春季年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Nucleic Acids Chemistry beyond the Watson-Crick Double Helix (70) : Prediction of DNA duplex stability having biased base composition under molecular crowding conditions2021

    • Author(s)
      Saptarshi Ghosh, Shuntaro Takahashi, Naoki Sugimoto
    • Organizer
      日本化学会第101春季年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 脱ワトソン・クリックの核酸化学 (66): 非天然DNAの複製反応に及ぼす分子クラウディングの影響2021

    • Author(s)
      高橋 俊太郎, Herdwijn Piet, 杉本 直己
    • Organizer
      日本化学会第101春季年会, オンライン開催
    • Related Report
      2020 Annual Research Report
  • [Presentation] cMyc遺伝子のグアニン四重らせんに対する圧力効果とその生物学的意義2020

    • Author(s)
      高橋俊太郎, 杉本直己
    • Organizer
      第61回高圧討論会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 局所的な細胞内環境における核酸構造の安定性を探る2020

    • Author(s)
      高橋俊太郎 , Ghosh Saptarshi, 杉本直己
    • Organizer
      第69回高分子討論会
    • Related Report
      2020 Annual Research Report
  • [Presentation] フラボノイドによるi-motif DNAの配列選択的な構造変化2020

    • Author(s)
      高橋俊太郎, BHOWMIK Sudipta, 杉本直己
    • Organizer
      第14回バイオ関連化学シンポジウム,
    • Related Report
      2020 Annual Research Report
  • [Presentation] Chemical regulation of gene expression based on the topology of DNA structures2020

    • Author(s)
      S.Takahashi
    • Organizer
      日本化学会第100回春季年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Nucleic Acids Chemistry beyond the Watson-Crick Double Helix(62): Transformation of selective i-motif DNAs induced by flavonoid2020

    • Author(s)
      S.Takahashi, B. Sudipta, N.Sugimoto
    • Organizer
      日本化学会第100回春季年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Topology-based DNA quadruplex sensors for characterization of intracellular crowding environments2019

    • Author(s)
      S. Takahashi, J. Yamamoto, A. Kitamura, M. Kinjo, N. Sugimoto
    • Organizer
      第46回国際核酸化学シンポジウム
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of ligand binding on G-quadruplex using high pressure2019

    • Author(s)
      S. Takahashi
    • Organizer
      The 7th International Meeting on Quadruplex Nucleic Acids
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Nucleic Acids Chemistry beyond the Watson-Crick Double Helix (48) :Imaging of crowding in cells by using guanine-quadruplex DNA2019

    • Author(s)
      S. Takahashi, J. Yamamoto, A. Kitamura, M. Kinjo, and N. Sugimoto
    • Organizer
      日本化学会第99回春季年会(2019)
    • Related Report
      2018 Research-status Report
  • [Presentation] グアニン四重鎖リガンドのトポロジー依存的結合様式によるDNA複製反応の制御2018

    • Author(s)
      高橋俊太郎, Bhowmik Sudipta, Chang Ta-Cha, 佐藤しのぶ, 竹中繁織, 杉本直己
    • Organizer
      第12回バイオ関連化学シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] リガンド複合型核酸マテリアルによる塩基損傷を受けたグアニン四重鎖の機能回復2018

    • Author(s)
      高橋俊太郎, Kim Byeang Hyean, Stetsenko Dmitry, Plavec Janez,杉本直己
    • Organizer
      第67回高分子討論会
    • Related Report
      2018 Research-status Report
  • [Presentation] Analysis of structural dynamics of RNA aptamer using high pressure2018

    • Author(s)
      S. Takahashi, T. Endoh, A. B. Rode, and N. Sugimoto
    • Organizer
      The 10th International Conference on High Pressure Bioscience and Biotechnology (HPBB2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Structural dynamics of RNA aptamer analyzed by volumetric approach2018

    • Author(s)
      S. Takahashi, T. Endoh, A. B. Rode, and N. Sugimoto
    • Organizer
      Advances in Noncanonical Nucleic Acids "ANNA2018"
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Transformation of selective i-motif DNAs into hairpin-like structures induced by a flavonoid compound2018

    • Author(s)
      S. Takahashi, S. Bhowmik, S. Ghosh, and N. Sugimoto
    • Organizer
      第45回国際核酸化学シンポジウム
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Topological effect of non-canonical DNA structures on DNA replication2017

    • Author(s)
      S. Takahashi, J. A. Brazier, and N. Sugimoto
    • Organizer
      第44回国際核酸化学シンポジウム
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Book] 核酸科学ハンドブック2020

    • Author(s)
      日本核酸化学会、杉本 直己
    • Total Pages
      576
    • Publisher
      講談社
    • ISBN
      9784065207864
    • Related Report
      2020 Annual Research Report
  • [Remarks] 甲南大学先端生命工学研究所ホームページ

    • URL

      http://www.konan-fiber.jp/indexb/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 甲南大学先端生命工学研究所ホームページ

    • URL

      http://www.konan-fiber.jp/index.php

    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2022-02-22  

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