mechanisms of chromosome regulation by Cdc7 kinase

2009 Fiscal Year Final Research Report

• Project/Area Number: 17080015
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: 財団法人東京都医学研究機構 (2009); Tokyo Metropolitan Organization for Medical Research (2005-2008)
• Principal Investigator: MASAI Hisao 財団法人東京都医学研究機構, 東京都臨床医学総合研究所, 参事研究員 (40229349)
• Project Period (FY): 2005 – 2009
• Keywords: DNA複製 / Cdc7キナーゼ / リン酸化 / 組換え開始 / 染色体サイクル / 複製フォー / ク停止 / DNA修復 / 染色体分配

Research Abstract

Cdc7 kinase plays critical roles in initiation of DNA replication. Additional important functions of Cdc7 in other chromosome transactions have been suggested. This includes meiotic recombination, DNA damage bypass (Trans-legion synthesis), and DNA replication checkpoint and so forth. We identified critical substrates of Cdc7 kinase in these processes. We also identified novel fission yeast mutations that can bypass the requirement of Hsk1 kinase for the growth. Characterization of these mutants lead to identification of some of the novel mechanisms that contribute to the plastic regulation of timing and site selection of origin firing.

Research Products

• [Journal Article] Pre-firing binding of Mrcl defines the early-firing origins which are selectively hyper-activated upon loss of fork stabilizing factors in fission yeast. (2011)
  • Author(s): Hayano, M., Kanoh, Y., Matsumoto, S., Kakusho, N., Masai, H.
  • Journal Title: Mol.Cell.Biol. 31 Pages: 2380-2391
• [Journal Article] Molecular mechanism of activation of human Cdc7 kinase : Bipartite interaction with Dbf4/ASK stimulates ATP binding and substrate recognition. (2011)
  • Author(s): Ryo Kitamura, Rino Fukatsu, Naoko Kakusho, Yong-Soon Cho, Chika Taniyama, Satoshi Yamazaki, Gaik-theng Toh, Kazuo Yanagi, Naoko Arai, Ho-Jin Chang, Hisao Masai
  • Journal Title: J.Biol.Chem. (In press)
• [Journal Article] Efficient expression and purification of human replication fork-stabilizing factor, Claspin, from mammalian cells : DNA binding activity and novel protein interactions. (2011)
  • Author(s): Uno, S., Masai, H.
  • Journal Title: Genes to Cells. (In press)
• [Journal Article] RecQL4 : a helicase linking formation and maintenance of a replication fork. (2011)
  • Author(s): Masai, H.
  • Journal Title: J.Biochem. (In press (commentary) )
• [Journal Article] Cdc7L1. (2011)
  • Author(s): Toh G-T., Masai, H.
  • Journal Title: UCSD-Nature Molecule Pages (in press (Review))
• [Journal Article] DDK phosphorylates checkpoint clamp Rad9 and promotes its release from damaged Chromatin. (2010)
  • Author(s): Furuya, K., Miyabe, I., Tsutsui, Y., Paderi, F., Kakusho, N., Masai, H., Niki, H., Carr, A.M.
  • Journal Title: Mol.Cell 40 Pages: 606-618
• [Journal Article] Cdc7-Mediated Radl8 Phosphorylation Directs the Accumulation of DNA Polymerase i1 at Sites of Stalled Replication. (2010)
  • Author(s): Day, T.A., Palle, K., Barkley, L.R., Kakusho, N., Zou, Y., Tateishi, S., Verreault, A., Masai, H., Vaziri, C.
  • Journal Title: J.Cell Biol. 191 Pages: 953-966
• [Journal Article] Hskl kinase and Cdc45 regulate replication stress-induced checkpoint responses in fission yeast. (2010)
  • Author(s): Matsumoto, S., Shimmoto, M., Kakusho, N., Yokoyama, M., Russell, P., Masai, H.
  • Journal Title: Cell Cycle 9 Pages: 4627-4637
• [Journal Article] Fission yeast Swil-Swi3 complex facilitates DNA binding of Mrc 1. (2010)
  • Author(s): Tanaka, T., Yokoyama, M., Matsumoto, S., Fukatsu, R., You, Z., う.
  • Journal Title: J.Biol.Chem. 285 Pages: 39609-39622
• [Journal Article] Eukaryotic DNA replication; where, when and how? (2010)
  • Author(s): Masai, H., Matsumoto, S., You, Z., Yoshizawa-Sugata, N., Oda, M.
  • Journal Title: Annual Rev.Biochem. 79 Pages: 89-130
• [Journal Article] Stalled replication forks : Making ends meet for recognition and stabilization. (2010)
  • Author(s): Masai, H., Tanaka, T., Kohda, D.
  • Journal Title: Bioessays(Review) 32, Pages: 687-697
• [Journal Article] Integrating DNA replication with Trans-Lesion Synthesis via Cdc7. (2010)
  • Author(s): Vaziri, C., Masai, H.
  • Journal Title: Cell Cycle Dec([Epub ahead of print] PMID : 21150323) 9(24) Pages: 15
• [Journal Article] Interactions between Swil-Swi3, Mrcl and S phase kinase, Hskl may regulate cellular responses to stalled replication forks in fission yeast. (2009)
  • Author(s): Shimmoto, S., Matsumoto, S., Hayano, M., Yokoyama, M., Noguchi, E., Russell, P., Masai, H.
  • Journal Title: Genes to Cells 14 Pages: 669-682
• [Journal Article] Drug Design with Cdc7 kinase, a potential novel cancer therapy target. (2009)
  • Author(s): Sawa, M., Masai, H.
  • Journal Title: Drug Design, Development and Therapy 2 Pages: 255-264
• [Journal Article] Cdc7 kinase is required for Claspin phosphorylation in DNA replication checkpoint. (2008)
  • Author(s): Kim, J-M., Kakusho, N., Yamada, M., Kanoh, Y., Takemoto, N., Masai, H.
  • Journal Title: Oncogene 27 Pages: 3475-3482
• [Journal Article] Cdc7-dependent phosphorylation of Mer2 facilitates initiation of yeast meiotic recombination. (2008)
  • Author(s): Sasanuma, H., Hirota, K., Fukuda, T., Kakusho, N., Kugou, N., Kawasaki, Y., Shibata, T., Masai, H Ohta, K.
  • Journal Title: Genes & Dev. 22 Pages: 398-410
• [Journal Article] Spatio-temporal dynamics of multicellular cell cycle progression. (2008)
  • Author(s): Sakaue-Sawano, A., Kurokawa, H., Morimura, T., Hanyu, A., Hama, H., Kashiwagi, S., Fukami, K., Imamura, T., Ogawa, M., Masai, H., Miyawaki, A.
  • Journal Title: Featured on the cover of the issue ell 132 Pages: 487-498
• [Journal Article] Cdc7 as a potential new target for cancer therapy. (2008)
  • Author(s): Ito, S., Taniyama, C., Arai, N., Masai, H.
  • Journal Title: Drug News and Perspectives(Featured on the cover of the issue) 21 Pages: 481-488
• [Journal Article] Identification of stimulators and inhibitors of CDC7 kinase in vitro. (2006)
  • Author(s): Kakusho, N., Taniyama, C., Masai, H.
  • Journal Title: Proc.Natl.Acad.Sci.USA 103 Pages: 8131-8136
• [Journal Article] Phosphorylation of MCM4 by Cdc7 kinase facilitateswith Cdc45 on the chromatin. (2006)
  • Author(s): Masai, H., Taniyama, C., Ogino, K., Matsui, E., Kakusho, N., Matsumoto, M., Kim, J-M., Ishii, A., Tanaka, T., Kobayashi, T., Tamai, K., Ohtani, K., Arai, K.
  • Journal Title: J.Biol.Chem. 281 Pages: 39249-32961
• [Journal Article] This paper was selected as "JBC paper of the week" and was featured in the cover of December 22 issue of JBC. A second human Dbf4/ASK-related protein, Drfl/ASKL1 is required for efficient completion of S and M phases. (2005)
  • Author(s): Yoshizawa-Sugata, N., Ishii, A., Taniyama, C., Matsui, E., Arai, K., Masai, H.
  • Journal Title: J.Biol.Chem. 280 Pages: 13062-13070
• [Journal Article] Functional analyses of mouse ASK, an activator subunit for Cdc7 kinase, using conditional ASK knockout ES cells. (2005)
  • Author(s): Yamashita, N., Kim, J-M., Koiwai, O., Arai, K., Masai, H.
  • Journal Title: Genes to Cells 50 Pages: 551-563
• [Journal Article] Novel human origins of DNA replication selected from a library of nascent DNA. (2005)
  • Author(s): Todorovic, V., Giadrossi, S., Pelizon, C., Masai, H., Giacca, M.
  • Journal Title: Mol.Cell 19 Pages: 567-575
• [Journal Article] Hskl-Dfpl/Himl, the Cdc7-Dbf4 Kinase in Schizosaccharomyces pombe, associates with Swi1, a component of the replication fork protection complex. (2005)
  • Author(s): Matsumoto, S., Ogino, K., Noguchi, E., Russell, P., Masai, H.
  • Journal Title: J.Biol.Chem. 280 Pages: 42536-42542
• [Journal Article] ASK
  • Author(s): Toh, G.K., Masai, H.
  • Journal Title: UCSD-Nature Molecule Pages(Review) Pages: Published online : 25 Feb 2009 doi:10.1038/mp.a000345.01
• [Book] なぜ親子は似るの?「なぜなぜ生物学」(東京化学同人) (2010)
  • Author(s): 正井久雄
  • Total Pages: 31-45
  • Publisher: MBSJ日本分子生物学会編
• [Book] 生物学辞典(分担)東京化学同人 (2010)
  • Author(s): 正井久雄
• [Book] 序蛋白質核酸酵素増刊号「染色体サイクル」(正井久雄、升方久夫、釣本敏樹、仁木宏典、篠原彰編集) (2009)
  • Author(s): 正井久雄
  • Total Pages: 307
  • Publisher: 共立出版
• [Book] 序論染色体サイクルの基礎蛋白質核酸酵素増刊号「染色体サイクル」(正井久雄、升方久夫、釣本敏樹、仁木宏典、篠原彰編集) (2009)
  • Author(s): 正井久雄
  • Total Pages: 311-316
  • Publisher: 共立出版
• [Book] 染色体サイクルの連係的制御機構概論蛋白質核酸酵素増刊号「染色体サイクル」(正井久雄、升方久夫、釣本敏樹、仁木宏典、篠原彰編集) (2009)
  • Author(s): 正井久雄
  • Total Pages: 521-523
  • Publisher: 共立出版
• [Book] Cdc7キナーゼによる染色体サイクル制御.蛋白質核酸酵素増刊号「染色体サイクル」(正井久雄、升方久夫、釣本敏樹、仁木宏典、篠原彰編集) (2009)
  • Author(s): 正井久雄
  • Total Pages: 524-530
  • Publisher: 共立出版
• [Book] 細胞周期をリアルタイムに可視化する技術.実験医学、増刊号「生命現象の動的理解を目指すライブイメージング」(宮脇敦史編集)26 (2008)
  • Author(s): 阪上-沢野朝子、正井久雄、宮脇敦史
  • Total Pages: 148-155
  • Publisher: 羊土社
• [Book] 序DNA複製研究の過去、現在、未来.細胞工学「細胞増殖とゲノム安定性維持のかなめ、DNA複製のメカニズム解明に迫る、(正井久雄編集)27 (2008)
  • Author(s): 正井久雄
  • Total Pages: 962-966
  • Publisher: 秀潤社
• [Book] DNA複製開始と進行のゲノムワイドのプロファイル解析.細胞工学「細胞増殖とゲノム安定性維持のかなめ、DNA複製のメカニズム解明に迫る」(正井久雄編集)27 (2008)
  • Author(s): 加納豊、正井久雄、白髭克彦
  • Total Pages: 1008-1012
  • Publisher: 秀潤社
• [Book] 「染色体サイクル:複製・分配組換え・修復・クロマチン制御のメカニズムとその異常による疾患」序文実験医学増刊号 (2007)
  • Author(s): 正井久雄
  • Publisher: 羊土社
• [Book] 概論"染色体サイクル制御の分子メカニズム"実験医学増刊号「染色体サイクル」 (2007)
  • Author(s): 正井久雄、渡邊嘉典
  • Total Pages: 16-23
  • Publisher: 羊土社
• [Book] MCMタンパク質のDNA複製における役割"実験医学増刊号「染色体サイクル」 (2007)
  • Author(s): YouZhiying, 正井久雄
  • Total Pages: 37-41
  • Publisher: 羊土社
• [Book] Cdc7キナーゼによる複製フォーク制御"実験医学増刊号「染色体サイクル」 (2007)
  • Author(s): 正井久雄、松本清治
  • Total Pages: 78-85
  • Publisher: 羊土社
• [Book] 生化学辞典(分担)第4版東京化学同人他12報 (2007)
  • Author(s): 正井久雄
• [Remarks] ホームページ等
  • URL: http://www.rinshoken.or.in/ors/CB/index-in.htm