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Coordination of chromosome behavior based on the replication of chromosomal 3D structure

Planned Research

Project AreaChromosome Orchestration System
Project/Area Number 15H05975
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionNational Institute of Genetics

Principal Investigator

ARAKI HIROYUKI  国立遺伝学研究所, 遺伝メカニズム研究系, 特任教授 (20151160)

Project Period (FY) 2015-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥124,540,000 (Direct Cost: ¥95,800,000、Indirect Cost: ¥28,740,000)
Fiscal Year 2019: ¥23,140,000 (Direct Cost: ¥17,800,000、Indirect Cost: ¥5,340,000)
Fiscal Year 2018: ¥23,270,000 (Direct Cost: ¥17,900,000、Indirect Cost: ¥5,370,000)
Fiscal Year 2017: ¥23,270,000 (Direct Cost: ¥17,900,000、Indirect Cost: ¥5,370,000)
Fiscal Year 2016: ¥23,140,000 (Direct Cost: ¥17,800,000、Indirect Cost: ¥5,340,000)
Fiscal Year 2015: ¥31,720,000 (Direct Cost: ¥24,400,000、Indirect Cost: ¥7,320,000)
KeywordsDNA複製 / 染色体 / 細胞周期 / DNA 複製 / 複製フォーク / 染色体動態 / クロマチン / 染色体構造 / in vitro系
Outline of Final Research Achievements

The in vitro DNA replication system was reconstituted from budding yeast purified proteins and optimized for analyses of chromosome dynamics. Using this reconstituted system, we have revealed a novel molecular mechanism of replication-origin loading of the pre-replicative complex at the initiation step of DNA replication, contribution of the interaction between DNA polymerase epsilon and GINS, a component of replicative helicase, to chromosomal DNA synthesis, and functional implication of the heterotetramer structure of the Sld3-Sld7 complex working for the initiation of DNA replication. We also established the in vitro system for pausing the replication forks and showed that DNA polymerase epsilon functions for pausing the replication fork.

Academic Significance and Societal Importance of the Research Achievements

真核生物の複数の複製タンパク質の機能を明らかにし、染色体動態との繋がりとして、複製フォークが停止する機構を解明した。これらの学術的意義も大きいが、解析に用いたin vitro複製系を稼働させたことも大きな意義がある。この系は、世界でも限られた研究室でしか動いておらず、国内では我々のところだけであった。この系を用いては、姉妹染色体間を結びつけるコヒーシンの導入を共同研究により行うなど、他の研究グループの指導も行ったので、国内においてもより多くの研究者がin vitro複製系を使用し、それぞれの研究に役立てることを期待している。。

Report

(6 results)
  • 2020 Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (38 results)

All 2020 2019 2018 2017 2016 2015

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 6 results,  Acknowledgement Compliant: 3 results) Presentation (27 results) (of which Int'l Joint Research: 14 results,  Invited: 16 results) Book (2 results)

  • [Journal Article] Recombination and Pol ζ rescue defective DNA replication upon impaired CMG helicase-Pol ε interaction.2020

    • Author(s)
      Denkiewicz-Kruk, M., Jedrychowska, M., Endo, S., Araki, H., Jonczyk, P., Dmowski, M., Fijalkowska, I.J.
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 21 Issue: 24 Pages: 9484-9484

    • DOI

      10.3390/ijms21249484

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Replication fork pausing at protein barriers on chromosomes2019

    • Author(s)
      Hizume Kohji、Araki Hiroyuki
    • Journal Title

      FEBS Letters

      Volume: 593 Issue: 13 Pages: 1449-1458

    • DOI

      10.1002/1873-3468.13481

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA polymerase e-dependent modulation of the pausing property of CMG helicase at the barrier.2018

    • Author(s)
      Hizume, K., Endo, S., Muramatsu, S., Kobayashi, T. and Araki, H.
    • Journal Title

      Genes & Dev

      Volume: 32 Issue: 19-20 Pages: 1315-1320

    • DOI

      10.1101/gad.317073.118

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pre‐initiation complex assembly functions as a molecular switch that splits the Mcm2‐7 double hexamer2017

    • Author(s)
      Miyazawa-Onami, M., Araki, H. and Tanaka, S
    • Journal Title

      EMBO Rep.

      Volume: 18 Issue: 10 Pages: 1752-1761

    • DOI

      10.15252/embr.201744206

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] New insights into the GINS complex explain the cntroversy between existing structural models.2017

    • Author(s)
      Carroni, M., March, M. D., Medagli, B., Krastanova, I., Taylor I. A., Amenitsch, H., Araki, H., Pisani, F. M., Patwardhan, A. and Onesti, S.
    • Journal Title

      Sci. Rep.

      Volume: 7 Issue: 1 Pages: 40188-40188

    • DOI

      10.1038/srep40188

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Flexible DNA path in the MCM double hexamer loaded on DNA2017

    • Author(s)
      Hizume, K., Kominami, H., Kobayashi, K., Yamada, H. and Araki, H.
    • Journal Title

      Biochemistry

      Volume: 印刷中 Issue: 19 Pages: 2435-2445

    • DOI

      10.1021/acs.biochem.6b00922

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Conserved interaction of Ctf18-RFC with DNA polymerase ε is critical for maintenance of genome stability in saccharomyces cerevisiae.2016

    • Author(s)
      Okimoto H, Tanaka S, Araki H, Ohashi E, Tsurimoto T.
    • Journal Title

      Genes Cells.

      Volume: in press Issue: 5 Pages: 482-491

    • DOI

      10.1111/gtc.12356

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Elucidating the DDK‐dependent step in replication initiation2016

    • Author(s)
      Araki, H
    • Journal Title

      EMBO J

      Volume: 35 Issue: 9 Pages: 907-908

    • DOI

      10.15252/embj.201694227

    • Related Report
      2015 Annual Research Report
  • [Journal Article] The quaternary structure of the eukaryotic DNA replication proteins Sld7 and Sld32015

    • Author(s)
      Itou, H., Shirakihara, Y. and Araki, H
    • Journal Title

      Acta Cryst.

      Volume: D71 Issue: 8 Pages: 1649-1656

    • DOI

      10.1107/s1399004715010457

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] DNA polymerase epsilon: its function at the initiation and elongation steps of chromosome replication2019

    • Author(s)
      荒木 弘之
    • Organizer
      Chromosome Dynamics
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Non enzymatic function of yeast DNA polymerase epsilon in chromosomal DNA replication2019

    • Author(s)
      Hiroyuki Araki, Shizuko Endo, Sachiko Muramatsu, Kohji Hizume
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 酵母を用いた複製機構の解析2019

    • Author(s)
      荒木 弘之
    • Organizer
      第25回DNA複製・組換え・修復ワークショップ
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Requirements for replication fork pausing at the barriers2019

    • Author(s)
      Koji Hizume, Shizuko Endo, Sachiko Muramatsu, Hiroyuki Araki
    • Organizer
      The 2019 meeting on Eukaryotic DNA Replication and Genome Maintenance
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Formation and progression of replication forks in budding yeast; replication fork pausing at the barriers2019

    • Author(s)
      Kohji Hizume, Shizuko Endo, Sachiko Muramatsu, Hiroyuki Araki
    • Organizer
      The 44th FEBS Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A novel role of DNA polymerase epsilon at replication forks; its involvement in replication fork pausing at the barriers2018

    • Author(s)
      Kohji Hizume, Shizuko Endo, Sachiko Muramatsu, Takehiko Kobayashi and Hiroyuki Araki
    • Organizer
      岡崎フラグメントー不連続DNA複製モデル50周年記念国際シンポジウム
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 出芽酵母の染色体DNA複製機構2018

    • Author(s)
      日詰光治、遠藤静子、村松佐知子、荒木弘之
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] DNA複製バリアにおける複製ファークの停止機構2018

    • Author(s)
      日詰光治、遠藤静子、村松佐知子、小林武彦、荒木弘之
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] DNA polymerase epsilon-dependent modulation of the pausing property of the CMG helices at the barrier2018

    • Author(s)
      Kohji Hizume, Shizuko Endo, Sachiko Muramatsu, Takehiko Kobayashi, Hiroyuki Araki
    • Organizer
      The 11th 3R & 3C Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 試験管内再構成系を用いた出芽酵母の染色体DNA複製機構の解析2018

    • Author(s)
      荒木弘之、遠藤静子、村松佐知子、日詰光治
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 染色体DNA上の障害によるDNA複製フォークの停止機構2018

    • Author(s)
      日詰光治、遠藤静子、村松佐知子、小林武彦、荒木弘之
    • Organizer
      第51回酵母遺伝学フォーラム年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Formation, progression and stalling of bidirectional replication forks in budding yeast2018

    • Author(s)
      Hiroyuki Araki
    • Organizer
      EMBO/EMBL Symposium: DNA replication: From basic biology to disease
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] CMG helices activity on chromatinized DNA and at the replication fork barrier2017

    • Author(s)
      日詰光治、遠藤静子、村松郁子、小林武彦、荒木弘之
    • Organizer
      The 2017 meeting on eukaryotic DNA replication & genome maintenance
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Structure and function of the Sld3-Sld7 complex essential for the initiation of chromosomal DNA replication2017

    • Author(s)
      Hiroyuki Araki, Shizuko Endo, Masaru Yagura, Sachiko Muramatsu, Koji Hizume, Izumi Ishizaki, Koji Kato, Min Yao
    • Organizer
      The 2017 meeting on eukaryotic DNA replication & genome maintenance
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] リーディング鎖ポリメラーゼPolε依存的な複製ヘリカーゼの停止反応2017

    • Author(s)
      日詰光治、遠藤静子、村松郁子、小林武彦、荒木弘之
    • Organizer
      第24回 DNA複製・組換え・修復ワークショップ
    • Related Report
      2016 Annual Research Report
  • [Presentation] 真核生物ヘリカーゼCMG複合体の、クロマチンあるいは複製バリア(Replication Fork Barrier)に対する活性の生化学的解析2017

    • Author(s)
      日詰光治、遠藤静子、村松郁子、小林武彦、荒木弘之
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 真核生物複製ヘリカーゼCMG複合体の進行阻害に関する生化学的研究2016

    • Author(s)
      日詰 光治、遠藤 静子、小林 武彦、荒木 弘之
    • Organizer
      第39回 日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] Molecular mechanism of chromosomal DNA replication in eukaryotes2016

    • Author(s)
      Hiroyuki Araki, Nishiho Makino, Masaru Yagura, Shizuko Endo, Sachiko Muramatsu, Hiroshi Itou, Kohji Hizume, Seiji Tanaka
    • Organizer
      The 39th Annual Meeting of the Molecular Biology society of Japan
    • Place of Presentation
      Yokohama
    • Year and Date
      2016-11-29
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] he initiation mechanism of chromosomal DNA replication ensuring bidirectional DNA synthesis in budding yeast2016

    • Author(s)
      Hiroyuki Araki, Nishiho Makino, Masaru Yagura, Shizuko Endo, Sachiko Muramatsu, Hiroshi Itou
    • Organizer
      10th 3R international symposium
    • Place of Presentation
      Matsue, Japan
    • Year and Date
      2016-11-13
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Biochemical analysis of the pausing of the eukaryotic replicative helices, CMG complex2016

    • Author(s)
      HIZUME, Kohji, Endo, Shizuko, Muramatsu, Ikuko, Kobayashi, Takehiko, ARAKI Hiroyuki
    • Organizer
      10th 3R International Symposium
    • Place of Presentation
      Matsue, Japan
    • Year and Date
      2016-11-13
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 出芽酵母のDNA複製開始複合体の形成機構2016

    • Author(s)
      荒木弘之、矢倉勝、牧野仁志穂、遠藤静子、村松佐知子、日詰光治、田中誠司
    • Organizer
      第89回日本生化学会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-25
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Molecular mechanism of eukaryotic DNA replication2016

    • Author(s)
      Araki, H.
    • Organizer
      Gordon Research Conference: Genomic instability
    • Place of Presentation
      Hongkong
    • Year and Date
      2016-07-24
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Bidirectional initiation of chromosomal DNA replication in budding yeast2016

    • Author(s)
      Hiroyuki Araki, Nishiho Makino, Masaru Yagura, Sachiko Muramatsu, Shizuko Endo, Hiroshi Itou
    • Organizer
      The 2016 Cold Spring Harbor Asia Conference: DNA metabolism, genomic stability and diseases
    • Place of Presentation
      Suzhou, China
    • Year and Date
      2016-06-13
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 真核生物複製ヘリカーゼCMG複合体のクロマチン基質に対する活性2015

    • Author(s)
      日詰光治、矢倉勝、遠藤静子、荒木 弘之
    • 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 Annual Research Report
  • [Presentation] 出芽酵母の複製開始複合体の形成機構2015

    • Author(s)
      矢倉勝、牧野仁志穂、伊藤啓、村松佐知子、日詰光治、田中尚美、田中誠司、荒木弘之
    • 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 Annual Research Report
    • Invited
  • [Presentation] Bidirectional initiation of chromosomal DNA replication in budding yeast2015

    • Author(s)
      Hiroyuki Araki, Hiroshi Itou, Nishiho Makino, Masaru Yagura, Shizuko Endo, Sachiko Muramatsu
    • Organizer
      2015 Cold Spring Harbor Meeting on "Eukaryotic DNA replication & genome maintenance"
    • Place of Presentation
      Cold Spring Harbor, NY, USA
    • Year and Date
      2015-09-01
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Nucleosome on helices activity of CMG complex2015

    • Author(s)
      Kohji Hizume, Shizuko Endo, Hiroyuki Araki
    • Organizer
      2015 Cold Spring Harbor Meeting on "Eukaryotic DNA replication & genome maintenance"
    • Place of Presentation
      Cold Spring Harbor, NY, USA
    • Year and Date
      2015-09-01
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Book] DNA replication, recombination, and repair2016

    • Author(s)
      Araki H. Hanaoka F, Sugasawa, K. 他
    • Total Pages
      555
    • Publisher
      Springer Japan
    • Related Report
      2015 Annual Research Report
  • [Book] The initiation of DNA replication in eukaryotes2016

    • Author(s)
      Tanaka S, Araki, H, Kaplan, DL. 他
    • Total Pages
      563
    • Publisher
      Springer International Publishing
    • Related Report
      2015 Annual Research Report

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Published: 2015-07-02   Modified: 2022-11-04  

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