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Novel insights for the cell cycle developed from analyses of a specific DNA bending factor

Research Project

Project/Area Number 21K19233
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
Research InstitutionKyushu University

Principal Investigator

Katayama Tsutomu  九州大学, 薬学研究院, 教授 (70264059)

Project Period (FY) 2021-07-09 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2023: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2022: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsDNA複製 / DnaA / DNA屈曲 / 複合体動態 / 細胞周期
Outline of Research at the Start

大腸菌IHFタンパク質は配列特異的にDNAに結合し鋭く屈曲させる。IHFによるDNA屈曲は、染色体の複製開始複合体の形成、核様体の構造形成、多様な遺伝子の転写や部位特異的組換え反応の制御などに重要であり、IHFはグローバルな制御因子としての役割を持つ。しかしながら、これまでIHFは細胞周期の制御因子としては重要視されていなかった。本計画は、複製開始タンパク質DnaAの活性化にもIHFが重要であるという研究代表者の独自発見を基盤にして、IHFの細胞周期制御システムにおける分子機構を新たに解明する。

Outline of Final Research Achievements

E. coli IHF protein is a DNA bender binding to DNA sequence-specifically. IHF binding supports the initiation of replication at the chromosomal origin, oriC as well as transcription regulation of various genes. DARS2 and datA are chromosomal DNA elements that control the activity of the replication initiation protein DnaA, and are timely activated depending on IHF binding. Before the replication initiation, DARS2 is temporarily activated by IHF binding, activating DnaA. After the replication initiation, datA is temporarily activated by IHF binding, inactivating DnaA. Here, multifaceted analyses were conducted to elucidate the mechanism underlying such controls. As a result, several novel candidate regulators of IHF binding were discovered. In particular, transcription readthrough from the tRNA operon upstream of datA was revealed to sustain timely dissociation of the datA-IHF complex. Multiple transcription termination mechanisms were also revealed to operate within the datA region.

Academic Significance and Societal Importance of the Research Achievements

datA-IHF複合体は複製開始因子DnaAの活性を抑制する。本研究では、datA-IHF複合体の解離はtRNAオペロンからの転写流入に依存することがわかった。tRNAの転写は細胞増殖が停止する増殖相やアミノ酸枯渇等によりタンパク質合成が阻害される環境(緊縮制御下)では阻害される。このような状況では、tRNAの転写阻害によりdatA-IHF複合体が構成的に形成され、DnaAの不活化を進める、と考えられる。つまり増殖相や環境応答、あるいは転写―翻訳系と連係した複製開始の新たな制御メカニズムが発見された。さらにDARS2-IHF複合体の新たな制御因子候補が見出されたことなども重要な進展と言える。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (35 results)

All 2024 2023 2022 2021 Other

All Journal Article (7 results) (of which Peer Reviewed: 6 results,  Open Access: 7 results) Presentation (24 results) (of which Int'l Joint Research: 8 results,  Invited: 7 results) Remarks (4 results)

  • [Journal Article] Read-through transcription of tRNA underlies the cell cycle-dependent dissociation of IHF from the DnaA-inactivating sequence datA2024

    • Author(s)
      Kasho Kazutoshi、Sakai Ryuji、Ito Kosuke、Nakagaki Wataru、Satomura Rion、Jinnouchi Takafumi、Ozaki Shogo、Katayama Tsutomu
    • Journal Title

      Frontiers in Microbiology

      Volume: 15 Pages: 1360108-1360108

    • DOI

      10.3389/fmicb.2024.1360108

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] IHF and Fis as Escherichia coli Cell Cycle Regulators: Activation of the Replication Origin oriC and the Regulatory Cycle of the DnaA Initiator2023

    • Author(s)
      Kasho Kazutoshi、Ozaki Shogo、Katayama Tsutomu
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 14 Pages: 11572-11572

    • DOI

      10.3390/ijms241411572

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single-stranded DNA recruitment mechanism in replication origin unwinding by DnaA initiator protein and HU, an evolutionary ubiquitous nucleoid protein2023

    • Author(s)
      Yoshida Ryusei、Ozaki Shogo、Kawakami Hironori、Katayama Tsutomu
    • Journal Title

      Nucleic Acids Research

      Volume: 51 Issue: 12 Pages: 6286-6306

    • DOI

      10.1093/nar/gkad389

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Thermotoga maritima oriC involves a DNA unwinding element with distinct modules and a DnaA-oligomerizing region with a novel directional binding mode2023

    • Author(s)
      Lu Chuyuan、Yoshida Ryusei、Katayama Tsutomu、Ozaki Shogo
    • Journal Title

      Journal of Biological Chemistry

      Volume: 299 Issue: 7 Pages: 104888-104888

    • DOI

      10.1016/j.jbc.2023.104888

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 核様体タンパク質から複製開始メカニズムの共通原理を展望する2023

    • Author(s)
      片山 勉、吉田竜星、川上広宣、加生和寿、尾崎省吾
    • Journal Title

      日本ゲノム微生物学会 ニュースレター

      Volume: 28 Pages: 2-5

    • Related Report
      2023 Annual Research Report
    • Open Access
  • [Journal Article] Whole-Genome Analysis Reveals That the Nucleoid Protein IHF Predominantly Binds to the Replication Origin oriC Specifically at the Time of Initiation2021

    • Author(s)
      Kasho Kazutoshi、Oshima Taku、Chumsakul Onuma、Nakamura Kensuke、Fukamachi Kazuki、Katayama Tsutomu
    • Journal Title

      Frontiers in Microbiology

      Volume: 12

    • DOI

      10.3389/fmicb.2021.697712

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Negative feedback for DARS2-Fis complex by ATP-DnaA supports the cell cycle-coordinated regulation for chromosome replication2021

    • Author(s)
      Miyoshi Kenya、Tatsumoto Yuka、Ozaki Shogo、Katayama Tsutomu
    • Journal Title

      Nucleic Acids Research

      Volume: 49 Issue: 22 Pages: 12820-12835

    • DOI

      10.1093/nar/gkab1171

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 大腸菌oriC-IHF-DnaA-DnaB-DnaC複合体の動態と新たな制御メカニズム2023

    • Author(s)
      片山 勉、鶴田 匠、呉 沁霏、興梠和真、吉田竜星、加生和寿、尾崎省吾
    • Organizer
      第27 回 DNA 複製・組換え・修復ワークショップ
    • Related Report
      2023 Annual Research Report
  • [Presentation] 大腸菌染色体の複製開始を制御するDNA因子datA、DARS2への核様体因子IHFの適時的結合を支えるメカニズムの解析2023

    • Author(s)
      加生 和寿、伊藤 孝輔、里村 龍音、吉田 瑞希、中薗 奨、片山 勉
    • Organizer
      第27 回 DNA 複製・組換え・修復ワークショップ
    • Related Report
      2023 Annual Research Report
  • [Presentation] 細菌種に高度に保存されたHUタンパク質はDnaA複合体の形成に依存して複製起点に結合しDUE開裂を進める2023

    • Author(s)
      吉田竜星、尾﨑省吾、川上広宣、片山 勉
    • Organizer
      第27 回 DNA 複製・組換え・修復ワークショップ
    • Related Report
      2023 Annual Research Report
  • [Presentation] 大腸菌の複製開始タイミング制御に必須の核様体因子 IHF を細胞周期に応じて制御する新規因子の探索2023

    • Author(s)
      加生和寿、伊藤孝輔、里村龍音、吉田瑞希、中薗 奨、片山 勉
    • Organizer
      令和5年度 日本生化学会九州支部例会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 細菌染色体の複製開始の分子機構:多様性に潜む普遍性2023

    • Author(s)
      片山 勉、吉田竜星、盧 楚元、鶴田 匠、若杉泰敬、加生和寿、尾崎省吾
    • Organizer
      日本遺伝学会第95回大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 大腸菌染色体の複製開始促進因子DARS2 とその活性化因子IHF との適時的相互作用を制御する因子の網羅的探索2023

    • Author(s)
      吉田瑞希、加生和寿、片山 勉
    • Organizer
      日本遺伝学会第95回大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] A common insight into mechanisms of duplex unwinding at the origin DNA during eubacterial chromosome replication2023

    • Author(s)
      Tsutomu Katayama
    • Organizer
      第96回 日本生化学会大会 シンポジウム「Novel Perspectives on Dynamic Mechanisms in Initiation Complexes and Initiation Regulation for Chromosome DNA Replication」(Organizer: Tsutomu Katayama)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 大腸菌の複製開始タイミングを統括的に制御するDNA屈曲因子IHFの結合・解離を細胞周期に応じて制御する新規因子の探索2023

    • Author(s)
      加生和寿、伊藤孝輔、里村龍音、吉田瑞希、中薗 奨、片山 勉
    • Organizer
      第96回 日本生化学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Precise regulation of replication initiation by timely binding and dissociation of the nucleoid protein IHF in Escherichia coli2023

    • Author(s)
      加生和寿、伊藤孝輔、里村龍音、吉田瑞希、中薗 奨、中垣 渉、片山 勉,
    • Organizer
      第46回日本分子物学会年会 シンポジウム
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] バクテリア染色体の複製開始メカニズムの普遍性と多様性を支えるDnaAタンパク質の分子機構2023

    • Author(s)
      片山 勉
    • Organizer
      2022年度国立遺伝学研究所研究会「単細胞生物に見られる生体プロセスの恒常性維持システム」
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Dynamic mechanisms constituting regulation for the replication initiator DnaA protein in Escherichia coli2022

    • Author(s)
      Tsutomu Katayama
    • Organizer
      Bacterial Physiology Meeting in Copenhagen 'Major Ideas in Quantitative Microbial Physiology: Past, Present and Future'
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 大腸菌の複製開始蛋白質DnaA の活性化を促す核様体蛋白質との相互作用における機能構造解析2022

    • Author(s)
      三善賢弥、加生和寿、片山 勉
    • Organizer
      令和4年度日本生化学会九州支部例会
    • Related Report
      2022 Research-status Report
  • [Presentation] バクテリア界における染色体複製起点の開裂反応の共通原理:核様体タンパク質HUとDnaAに依存した複製起点開裂の分子機構2022

    • Author(s)
      吉田竜星、尾﨑省吾、川上広宣、片山 勉
    • Organizer
      第18回21世紀大腸菌研究会
    • Related Report
      2022 Research-status Report
  • [Presentation] Dynamic nucleoprotein complexes sustaining regulation for the chromosomal replication initiation in Escherichia coli2022

    • Author(s)
      Tsutomu Katayama
    • Organizer
      NIG International Symposium 2022: Chromosome Replication in the New Era - Old and New Questions in Life Science
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Regulation of replication initiation timing by timely binding and dissociation of the nucleoid protein IHF in Escherichia coli2022

    • Author(s)
      Kazutoshi Kasho, Taku Oshima, Onuma Chumsakul, Kensuke Nakamura, Kazuki Fukamachi, Kazuyuki Fujimitsu, and Tsutomu Katayama
    • Organizer
      NIG International Symposium 2022: Chromosome Replication in the New Era - Old and New Questions in Life Science
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mechanisms for bacterial origin unwinding mediated by DnaA and HU, a ubiquitous nucleoid-associated protein2022

    • Author(s)
      Ryusei Yoshida, Shogo Ozaki, Hironori Kawakami, and Tsutomu Katayama
    • Organizer
      NIG International Symposium 2022: Chromosome Replication in the New Era - Old and New Questions in Life Science
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 複製開始因子DnaAを適時的に不活性化するdatA-IHF複合体の形成を制御する転写の分子機構2022

    • Author(s)
      伊藤孝輔, 酒井隆至, 加生和寿, 尾崎省吾, 片山 勉
    • Organizer
      第45回日本分子生物学会年会ワークショップ「微生物の分子生物学・再考」
    • Related Report
      2022 Research-status Report
  • [Presentation] 複製開始促進DNA因子DARS2を活性化する核様体蛋白質IHFの結合制御因子の探索2021

    • Author(s)
      李 藍楊、三善賢弥、辰本優香、尾崎省吾、片山 勉
    • Organizer
      令和3年度日本生化学会九州支部例会
    • Related Report
      2021 Research-status Report
  • [Presentation] Regulatory systems underlying the replication cycle of the chromosome in eubacteria2021

    • Author(s)
      Tsutomu Katayama
    • Organizer
      The 6th JAPAN-TAIWAN Joint Symposium For Pharmaceutical Sciences
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 大腸菌複製開始蛋白質DnaAの活性化因子DARS2はATP-DnaAを介する負のフィードバックにより機能制御される2021

    • Author(s)
      三善賢弥、辰本優香、尾崎省吾、片山 勉
    • Organizer
      日本遺伝学会第93回大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 大腸菌染色体の複製開始因子ATP-DnaA がもつフィードバック制御メカニズム2021

    • Author(s)
      片山 勉、三善賢弥、吉田竜星、辰本優香、盧 楚元、興梠和真、伊藤孝輔、加生和寿、尾崎省吾
    • Organizer
      第26回 DNA 複製・組換え・修復ワークショップ
    • Related Report
      2021 Research-status Report
  • [Presentation] 大腸菌の核様体蛋白質IHFはゲノム複製開始時期において複製開始点oriCと特異的に結合する2021

    • Author(s)
      加生和寿、大島 拓、Onuma Chumsakul、中村健介、深町和貴、片山 勉
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 大腸菌染色体の複製と細胞周期制御を支えるタンパク質高次複合体のダイナミクス2021

    • Author(s)
      片山 勉、吉田竜星、三善賢弥、盧 楚元、辰本優香、李 藍楊、伊藤孝輔、川上広宣、加生和寿、尾崎省吾
    • Organizer
      第94回日本生化学会大会 シンポジウム「染色体の多様な機能を支えるタンパク質高次複合体」
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Dynamic nucleoprotein complexes and DNA structural changes supporting regulated replication initiation of the Escherichia coli chromosome2021

    • Author(s)
      Tsutomu Katayama, Kenya Miyoshi, Ryusei Yoshida, Chuyuan Lu, Lanyang Li, Kazuma Korogi, Yuka Tatsumoto, Kosuke Ito, Hironori Kawakami, Kazutoshi Kasho, Shogo Ozaki
    • Organizer
      第44回日本分子生物学会年会 シンポジウム「The common mechanism for regulation of genome maintenance by DNA structural dynamics」
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] 九州大学大学院薬学研究院_分子生物薬学分野

    • URL

      http://bunsei.phar.kyushu-u.ac.jp

    • Related Report
      2023 Annual Research Report 2022 Research-status Report 2021 Research-status Report
  • [Remarks] 九州大学研究者情報_片山 勉

    • URL

      http://hyoka.ofc.kyushu-u.ac.jp/search/details/K001101/index.html

    • Related Report
      2023 Annual Research Report 2022 Research-status Report 2021 Research-status Report
  • [Remarks] 九州大学薬学研究院_研究成果

    • URL

      https://www.phar.kyushu-u.ac.jp/topics/view.php?page=1&B_Code=586

    • Related Report
      2021 Research-status Report
  • [Remarks] 九州大学_研究成果

    • URL

      https://www.kyushu-u.ac.jp/ja/researches/view/721

    • Related Report
      2021 Research-status Report

URL: 

Published: 2021-07-13   Modified: 2025-01-30  

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