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Molecular mechanism of the initiation in eukaryotic chromosomal DNA replication

Research Project

Project/Area Number 25251005
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Molecular biology
Research InstitutionNational Institute of Genetics

Principal Investigator

ARAKI Hiroyuki  国立遺伝学研究所, 細胞遺伝研究系, 教授 (20151160)

Co-Investigator(Kenkyū-buntansha) HIZUME Kohji  国立遺伝学研究所, 細胞遺伝研究系, 助教 (10378846)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥46,800,000 (Direct Cost: ¥36,000,000、Indirect Cost: ¥10,800,000)
Fiscal Year 2015: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
Fiscal Year 2014: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2013: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
KeywordsDNA複製 / 細胞周期 / クロマチン / 酵母 / 染色体 / 複製開始
Outline of Final Research Achievements

Double-stranded DNA must be unwound to single-stranded DNA to initiate DNA replication. Mcm2-7, the core of the helicase that unwinds DNA, is loaded to replication origins first and then Cdc45 and GINS associate with the loaded Mcm2-7 to form an active helicase. We reveal that the Sld3-Sld7 complex, which is essential for this activation, comprises two Sld3 molecules connected by two Sld7 molecules and suggest that this structure is important for the initiation of DNA replication. Moreover, we confirm that DNA polymerase epsilon also works for this activation step. We further devise the way to analyze the relationship between chromatin, cell cycle checkpoints and DNA replication.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (37 results)

All 2016 2015 2014 2013 Other

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Acknowledgement Compliant: 4 results,  Open Access: 3 results) Presentation (25 results) (of which Int'l Joint Research: 3 results,  Invited: 6 results) Book (1 results) Remarks (3 results)

  • [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] Molecular mechanism of DNA replication.2016

    • Author(s)
      Araki, H.
    • Journal Title

      DNA replication, recombination, and repair (eds. F. Hanaoka and K. Sugasawa)

      Pages: 3-22

    • DOI

      10.1007/978-4-431-55873-6_1

    • ISBN
      9784431558712, 9784431558736
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of CDK in replication initiation2016

    • Author(s)
      Tanaka, S. and Araki, H.
    • Journal Title

      The initiation of DNA replication in eukaryotes (ed. D. Kaplan)

      Pages: 263-278

    • DOI

      10.1007/978-3-319-24696-3_13

    • ISBN
      9783319246949, 9783319246963
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [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] Fidelity consequences of the impaired interaction between DNA polymerase epsilon and the GINS complex2015

    • Author(s)
      Garbacz, M., Araki, H., Flis, K., Bebenek, A., Zawada, A., Jonczyk, P., Makiela-Dzbenska, K. and Fijiakowska, I. J.
    • Journal Title

      DNA repair

      Volume: 29 Pages: 23-35

    • DOI

      10.1016/j.dnarep.2015.02.007

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [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
  • [Journal Article] Crystal structure of the homology domain of the eukaryotic DNA replication proteins Sld3/Treslin2014

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

      Structure

      Volume: 22 Issue: 9 Pages: 1341-1347

    • DOI

      10.1016/j.str.2014.07.001

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Concerted interaction between origin recognition complex (ORC), nucleosomes, and replication origin DNA ensures stable ORC-origin binding2013

    • Author(s)
      Hizume, K., Yagura, M. and Araki, H.
    • Journal Title

      Genes Cells

      Volume: 18 Issue: 9 Pages: 764-779

    • DOI

      10.1111/gtc.12073

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [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
      2015-12-03
    • Related Report
      2015 Annual Research Report
  • [Presentation] 複製ヘリカーゼCMG複合体によるクロマチン鎖開裂反応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] Switch-like assembly of pre-initiation complex in the initiation of DNA replication2015

    • Author(s)
      大浪真由美、荒木弘之、田中誠司
    • Organizer
      第23回DNA複製・組換え・修復ワークショップ
    • Place of Presentation
      焼津
    • Year and Date
      2015-10-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 複製ヘリカーゼCMG複合体によるクロマチン鎖開裂反応2015

    • Author(s)
      日詰光治、遠藤静子、荒木弘之
    • Organizer
      第23回DNA複製・組換え・修復ワークショップ
    • Place of Presentation
      焼津
    • Year and Date
      2015-10-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 出芽酵母の複製複合体の形成機構2015

    • Author(s)
      牧野仁志穂、矢倉勝、伊藤啓、村松佐知子、荒木弘之
    • Organizer
      第23回DNA複製・組換え・修復ワークショップ
    • Place of Presentation
      焼津
    • Year and Date
      2015-10-20
    • Related Report
      2015 Annual Research Report
  • [Presentation] Dissection of the initiation reaction of DNA replication in budding yeast2015

    • Author(s)
      Ohnami, M., Araki, H. and Tanaka, S.
    • Organizer
      2015 Cold Spring Harbor Meeting on "Eukaryotic DNA replication & genome maintenance"
    • Place of Presentation
      Cold Spring Harbor, NY, USA
    • Year and Date
      2015-09-03
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Bidirectional initiation of chromosomal DNA replication in budding yeast2015

    • Author(s)
      Araki, H., Itou, H., Makino, N., Yagura, M., Endo, S. and Muramatsu, S.
    • Organizer
      2015 Cold Spring Harbor Meeting on "Eukaryotic DNA replication & genome maintenance"
    • Place of Presentation
      Cold Spring Harbor, NY, USA
    • Year and Date
      2015-09-02
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Nucleosome on helices activity of CMG complex2015

    • Author(s)
      Hizume, K., Endo, S. and Araki, H.
    • Organizer
      2015 Cold Spring Harbor Meeting on "Eukaryotic DNA replication & genome maintenance"
    • Place of Presentation
      Cold Spring Harbor, NY, USA
    • Year and Date
      2015-09-02
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 出芽酵母染色体DNAの複製開始機構2014

    • Author(s)
      荒木 弘之、伊藤啓、矢倉勝、村松佐知子、牧野仁志穂、日詰光治
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Year and Date
      2014-11-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] MCM-DNA複合体の原子間力顕微鏡による可視化解析2014

    • Author(s)
      Kohji Hizume, Hiroyuki Araki
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Year and Date
      2014-11-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Molecular mechanism that ensures bidirectional initiation of chromosomal DNA replication in budding yeast2014

    • Author(s)
      Hiroyuki Araki, Masaru Yagura, Nishiho Makino, Shizuko Endo, Kei Itou, Sachiko Muramatsu, Yoshimi Tanaka, Kohji Hizume, Seiji Tanaka
    • Organizer
      The 9th 3R Symposium (International Symposium on DNA Replication, Recombination and Repair)
    • Place of Presentation
      御殿場(御殿場高原ホテル)
    • Year and Date
      2014-11-21
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Nucleosome on helicase activity of CMG complex2014

    • Author(s)
      Kohji Hizume, Masaru Yagura, Shizuko Endo, and Hiroyuki Araki
    • Organizer
      The 9th 3R Symposium (International Symposium on DNA Replication, Recombination and Repair)
    • Place of Presentation
      御殿場(御殿場高原ホテル)
    • Year and Date
      2014-11-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] The cell cycle regulated initiation mechanism of chromosomal DNA replication in budding yeast2014

    • Author(s)
      Hiroyuki Araki
    • Organizer
      国際生化学・分子生物学会
    • Place of Presentation
      台北、台湾
    • Year and Date
      2014-10-23
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Connection between the initiation of DNA replication and structural change of chromatin2014

    • Author(s)
      Tanaka S., Araki H.
    • Organizer
      新学術「ゲノム普遍的制御」国際シンポジウム
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] Establishment of replication forks at origins2013

    • Author(s)
      Araki, H.
    • Organizer
      ゲノム不安定性・進化・ヒトの疾病会議
    • Place of Presentation
      サンクトペテルブルグ、ロシア
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Formation of active replicative helicase in budding yeast2013

    • Author(s)
      Araki H., Yagura M., Makino N., Tanaka Y., Itou H., Hizume K., and Tanaka S.
    • Organizer
      2013 Cold Spring Harbor Laboratory Meeting on EUKARYOTIC DNA REPLICATION & GENOME MAINTENANCE
    • Place of Presentation
      Cold Spring Harbor, NY(USA)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Dpb11/TopBP1-GINS interaction is required for efficient initiation of DNA replication2013

    • Author(s)
      Tanaka, S., Komeda,Y., Umemori,T., Kubota,Y., Takisawa,H., and Araki,H.
    • Organizer
      2013 Cold Spring Harbor Laboratory Meeting on EUKARYOTIC DNA REPLICATION & GENOME MAINTENANCE
    • Place of Presentation
      Cold Spring Harbor, NY(USA)
    • Related Report
      2013 Annual Research Report
  • [Presentation] In vitro study of the initiation of chromosomal DNA replication in budding yeast2013

    • Author(s)
      Yagura, M. Araki H.
    • Organizer
      2013 Cold Spring Harbor Laboratory Meeting on EUKARYOTIC DNA REPLICATION & GENOME MAINTENANCE
    • Place of Presentation
      Cold Spring Harbor, NY(USA)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Molecular mechanism of initiation of chromosomal DNA replication in eukaryotic cells2013

    • Author(s)
      Araki H., Makino N., Yagura M., Tanaka Y., Hizume K., and Tanaka S.
    • Organizer
      日本遺伝学会第85回大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ORCの複製開始点特異的な結合に寄与するORC/nucleosome/複製開始点DNA間の協調的相互作用2013

    • Author(s)
      日詰光治、矢倉勝、荒木弘之
    • Organizer
      DNA複製・組換え・修復ワークショップ
    • Place of Presentation
      仙台
    • Related Report
      2013 Annual Research Report
  • [Presentation] 試験管内反応系を用いた真核生物染色体DNA複製開始機構の解析2013

    • Author(s)
      矢倉勝、 田中尚美、 柳沢好美 、荒木弘之
    • Organizer
      DNA複製・組換え・修復ワークショップ
    • Place of Presentation
      仙台
    • Related Report
      2013 Annual Research Report
  • [Presentation] クロマチンファイバー上でのDNA複製のライセンシング:原子間力顕微鏡による可視化解析2013

    • Author(s)
      日詰光治、矢倉勝、荒木弘之
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] DNA複製開始制御とクロマチン構造変換の接点2013

    • Author(s)
      田中 誠司、大浪 真由美、荒木弘之
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] In vitro study of the initiation of chromosomal DNA replication in budding yeast2013

    • Author(s)
      Yagura, M. Araki H.
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] 真核生物DNA複製の開始制御におけるクロマチン上への複製開始因子集合の観察2013

    • Author(s)
      日詰光治、矢倉勝、荒木弘之
    • Organizer
      日本顕微鏡学会 走査型プローブ顕微鏡分科会
    • Place of Presentation
      新潟県南魚沼郡
    • Related Report
      2013 Annual Research Report
  • [Book] DNA replication2013

    • Author(s)
      Tanaka, S. and Araki, H.
    • Total Pages
      561
    • Publisher
      Cold Spring Harbor Press
    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://www.nig.ac.jp/Research-Highlights/1468/1552.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] Araki Lab.

    • URL

      http://www.nig.ac.jp/labs/MicGen/index.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] DNA複製のスタート地点の決定における、クロマチンの役割

    • URL

      http://www.nig.ac.jp/Research-Highlights/1170/1270.html

    • Related Report
      2013 Annual Research Report

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

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