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ゲノム複製プログラム制御におけるゲノムアダプテーションの分子機構

Publicly Offered Research

Project AreaSystematic study of chromosome adaptation
Project/Area Number 25125724
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 InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

正井 久雄  公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 基盤技術研究センター長 (40229349)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2013: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Keywords複製プログラム / 複製起点 / 複製タイミング / Cdc7キナーゼ / チェックポイント / DNA損傷 / 栄養条件 / Rif1 / 染色体ドメイン / グルコース
Outline of Annual Research Achievements

1 出芽酵母を用いてDSB導入によりその近傍のdormant ori (休眠複製起点)が活性化されるメカニズムを検討する。1) DSB導入前と後でRif1およびKu複合体の結合部位は変動していなかった。しかし、DSB導入部位の近傍に強いRif1結合部位を同定した。2) ChIP-Seqにより、出芽酵母ゲノム全体におけるRif1の結合部位を決定した。
2 ゲノムワイドの複製プログラム制御に及ぼす因子の解析 1) cohesion, condensing, CTCFなどのknockdown が複製タイミングに及ぼす影響を調べた。しかし、顕著の影響は観察されなかった。同じ条件下でRif1KDは複製タイミングをゲノムワイドに大きく変化させる。
3 チェックポイントによる局所的複製プログラム制御機構 1)Mrc1はチェックポイント依存的と非依存的の二つの独立の経路で複製タイミングを制御することが明らかとなった。 2) チェックポイント非依存的な複製開始抑制経路はMrc1上のHBSドメインに依存する。ここにはHsk1キナーゼが結合し、Mrc1をリン酸化することによりそのconformationを変化させ、活性型に変化させる。HSBが欠損すると、Mrc1は常に活性化型になるためにHsk1をバイパスできると考えられる。
4 Rif1の染色体結合部位をChIP-Seqで解析するために免疫沈降可能な新規抗体を作製した。この抗体はChIPに使用可能であることが明らかになったので、マウスES細胞を用いて、まずRif1欠損により遺伝子発現が大きく変動する遺伝子領域の近傍にRif1が結合するかどうかをChIP-qPCRにより検討した。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (27 results)

All 2015 2014 2013

All Journal Article (14 results) (of which Peer Reviewed: 14 results,  Open Access: 14 results,  Acknowledgement Compliant: 13 results) Presentation (12 results) (of which Invited: 12 results) Book (1 results)

  • [Journal Article] CDC28 phosphorylates Cac1p and regulates the association of Chromatin Assembly Factor I with chromatin.2015

    • Author(s)
      Jeffery, D., Kakusho, N., You, Z., Gharib, M., Wyse, B., Drury, E., Weinreich, M., Thibault, P. Verreault, A., Masai, H. and Yankulov, K.
    • Journal Title

      Cell Cycle

      Volume: 14 Pages: 74-85

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Definition of the transcription factor TdIF1 consensus binding sequence through genome-wide mapping of its binding sites.2015

    • Author(s)
      Kotaro Koiwai, Takashi Kubota, Nobuhisa Watanabe, Katsutoshi Hori, Osamu Koiwai and Hisao Masai
    • Journal Title

      Genes to Cells

      Volume: 20 Issue: 3 Pages: 242-254

    • DOI

      10.1111/gtc.12216

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] NCOA4 Transcriptional Coactivator Inhibits Activation of DNA Replication Origins.2014

    • Author(s)
      Bellelli, R., Castellone, M.D., Guida, T., Limongello, R., Dathan, N.A., Merolla, F., Cirafici, A.M., Affuso, A., Masai, H., Costanzo, V., Grieco, D., Fusco, A., Santoro, M., and Carlomagno, F.
    • Journal Title

      Mol. Cell

      Volume: 55 Issue: 1 Pages: 123-137

    • DOI

      10.1016/j.molcel.2014.04.031

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Regulation and roles of Cdc7 kinase under replication stress.2014

    • Author(s)
      Yamada, M., Masai, H., and Bartek, J.
    • Journal Title

      Cell Cycle

      Volume: 13 Issue: 12 Pages: 1859-1866

    • DOI

      10.4161/cc.29251

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cell cycle synchronization and flow cytometry analysis of mammalian cell.2014

    • Author(s)
      Yoshizawa-Sugata, N. and Masai, H.
    • Journal Title

      Methods in Molecular Biology

      Volume: 1170 Pages: 279-293

    • DOI

      10.1007/978-1-4939-0888-2_13

    • ISBN
      9781493908875, 9781493908882
    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] ATM in prevention of genomic instability.2014

    • Author(s)
      Hisao Masai
    • Journal Title

      Cell Cycle

      Volume: 13 Issue: 6 Pages: 882-883

    • DOI

      10.4161/cc.28216

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Temporal and spatial regulation of eukaryotic DNA replication: from regulated initiation to genome-scale timing program.2014

    • Author(s)
      Renard-Guillet, C., Kanoh, Y., Shirahige, K., and Masai, H.
    • Journal Title

      Seminars in Cell & Developmental Biology,

      Volume: 30 Pages: 110-120

    • DOI

      10.1016/j.semcdb.2014.04.014

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] ATR-Chk1-APC/CCdh1-dependent stabilization of Cdc7-ASK(Dbf4) kinase complex is required for DNA damage bypass under replication stress.2013

    • Author(s)
      Yamada, M., Watanabe, K., Mistrik, M., Mailand, N., Lee, M-H., Masai, H., Lukas, J. and Bartek, B.
    • Journal Title

      Genes and Development

      Volume: 27 Issue: 22 Pages: 2459-72

    • DOI

      10.1101/gad.224568.113

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The Human Tim/Tipin Complex Directly Interacts with DNA Polymerase {epsilon} and Stimulates its Synthetic Activity.2013

    • Author(s)
      Aria, V., De Felice, M., Di Perna, R., Uno, S., Masai, H., Syvaoja, J.E., van Loon, B., Hubscher, U. and Pisani, F.M.
    • Journal Title

      J. Biol. Chem.

      Volume: 288 Issue: 18 Pages: 12742-12752

    • DOI

      10.1074/jbc.m112.398073

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Analysis of epigenetic stability and conversions in Saccharomyces cerevisiae reveals a novel role of CAF-I in position-effect variegation.2013

    • Author(s)
      Jeffery, D.C., Wyse, B.A., Rehman, M.A., Brown, G.W., You, Z., Oshidari, R., Masai, H. and Yankulov, K.Y.
    • Journal Title

      Nucleic Acids Res.

      Volume: 41 Issue: 18 Pages: 8475-8488

    • DOI

      10.1093/nar/gkt623

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Role of multifunctional transcription factor TFII-I and putative tumour suppressor DBC1 in cell cycle and DNA double strand damage repair2013

    • Author(s)
      Tanikawa, M., Wada-Hiraike, O., Yoshizawa-Sugata, N., Shirane A, Hirano M, Hiraike H, Miyamoto, Y., Sone, K., Ikeda, Y., Kashiyama, T., Oda K, Kawana K, Katakura Y, Yano T, Masai, H., Roy AL, Osuga, Y. and Fujii, T.
    • Journal Title

      Br. J. Cancer.

      Volume: 109 Issue: 12 Pages: 3042

    • DOI

      10.1038/bjc.2013.532

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Replication timing regulation of eukaryotic replicons: Rif1 as a global regulator of replication timing.2013

    • Author(s)
      Yamazaki, S. Hayano, M. and Masai, H.
    • Journal Title

      Trends in Genetics

      Volume: 29 Issue: 8 Pages: 449-460

    • DOI

      10.1016/j.tig.2013.05.001

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A personal reflection on the Replicon Theory: from R1 plasmid to replication timing regulation in human cells2013

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

      J. Mol. Biol.

      Volume: 425 Issue: 23 Pages: 4663-4672

    • DOI

      10.1016/j.jmb.2013.03.039

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Regulation of chromosome dynamics by Hsk1 kinase2013

    • Author(s)
      Matsumoto, S. and Masai, H.
    • Journal Title

      Biochemical Society Transactions

      Volume: 41 Issue: 6 Pages: 1712-1719

    • DOI

      10.1042/bst20130217

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Conserved mechanisms and diversity of genome DNA replication: from bacteria to human2014

    • Author(s)
      正井 久雄
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Regulation of mammalian Mcm helicase complexes2014

    • Author(s)
      Hisao Masai, You Zhiying, Koji L. Ode, Naoko Kakusho, Rino Fukatsu, and Haruhiko Takisawa
    • Organizer
      第87回日本生化学会大会シンポジウム「ゲノムを支えるDNAヘリカーゼの動態を探求する新たな研究展開」
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 染色体DNA複製プログラムの制御機構2014

    • Author(s)
      正井 久雄
    • Organizer
      大阪大学蛋白質研究所セミナー「染色体伝承の分子背景:複製から染色体分離まで」
    • Place of Presentation
      大阪大学(大阪)
    • Year and Date
      2014-09-25 – 2014-09-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Regulation of DNA replication program in fission yeast and human cells2014

    • Author(s)
      Hisao Masai
    • Organizer
      Marco Foiani(Italy, Milan)教授の招聘により IFOM Foundation – F.I.R.C. Institute of Molecular Oncology Foundationで講演
    • Place of Presentation
      Italia, Milan
    • Year and Date
      2014-09-16
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Mrc1/Claspinの分子内相互作用による活性制御および新規機能2014

    • Author(s)
      正井 久雄
    • Organizer
      九州大学 大学院薬学研究院 招聘研究セミナー
    • Place of Presentation
      九州大学 (福岡)
    • Year and Date
      2014-08-29
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Regulation of replication program in fission yeast and human cells2014

    • Author(s)
      Hisao Masai
    • Organizer
      Peking University(特別招聘講演)
    • Place of Presentation
      Peking University(中国)
    • Year and Date
      2014-05-16
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 染色体DNA複製プログラムの制御機構と起源・進化2014

    • Author(s)
      正井 久雄、田中 卓、加納 豊、山崎 聡志、松本 清治、吉沢 直子、松嶋 夢叶
    • Organizer
      第2回 細胞周期制御と細胞運命 シンポジウム
    • Place of Presentation
      浜松(静岡)
    • Year and Date
      2014-02-13 – 2014-02-14
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] イントロダクション2013

    • Author(s)
      正井 久雄
    • Organizer
      第36回(2013年)日本分子生物学会年会,ワークショップ 『レプリコン仮説50周年:染色体複製装置の形成とその活性の時空間制御』
    • Place of Presentation
      神戸ポートアイランド(兵庫)
    • Year and Date
      2013-12-03 – 2013-12-06
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Rif1: a potential global regulator of DNA replication, DNA repair, and recombination2013

    • Author(s)
      正井 久雄、山崎 聡志、Lai Mongsing、Foiani Marco、吉沢 直子、加納 豊、松本 清治、森山賢治、覺正 直子、深津 理乃、松嶋 夢叶、河野 暢明、Renard-Guillet Claire
    • Organizer
      第36回(2013年)日本分子生物学会年会,ワークショップ 『DNA二重鎖切断のend-resectionと修復機構の選択・制御』
    • Place of Presentation
      神戸ポートアイランド(兵庫)
    • Year and Date
      2013-12-03 – 2013-12-06
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Introduction" Symposium,2013

    • Author(s)
      Hisao Masai
    • Organizer
      86th Annual Meeting of the Japanese Biochemical Society
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2013-09-11 – 2013-09-13
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Chromatin architecture that regulates replication timing of eukaryotic chromosomes2013

    • Author(s)
      Hisao Masai, Yutaka Kanoh, Satoshi Yamazaki, Motoshi Hayano, Naoko Yoshizawa, Kenji Moriyama, Yumeka Matsushima, Naoko Kakusho, Rino Fukatsu
    • Organizer
      第86回日本生化学会大会事務局 インターナショナルセッション『Assembly and architecture of protein complexes regulating inheritance and stable maintenance of genome』
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2013-09-11 – 2013-09-13
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Control of origin firing timing in fission yeast cells2013

    • Author(s)
      Hisao Masai
    • Organizer
      EMBO Conference "Pombe 2013: 7th International Fission Yeast Meeting
    • Place of Presentation
      London UK
    • Year and Date
      2013-06-24 – 2013-06-29
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Book] DNA Replication, Recombination and Repair: Molecular Mechanisms and Pathology2015

    • Author(s)
      Motoshi Hayano, Seiji Matsumoto and Hisao Masai
    • Publisher
      Springer
    • Related Report
      2014 Annual Research Report

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Published: 2013-05-15   Modified: 2018-03-28  

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