The molecular mechanism of quiescent state

• Project/Area Number: 19770177
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Cell biology
• Research Institution: Nagoya City University
• Principal Investigator: SHIMADA Midori Nagoya City University, 大学院・医学研究科, 助教 (60444981)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,880,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: 細胞周期 / DNA損傷 / チェックポイント / 転写 / クロマチン

Research Abstract

DNA損傷により様々な遺伝子の発現が変化することが知られている。これまで転写誘導を引き起こす機構について多くの報告があるが、転写抑制をもたらす機構はほとんど知られていない。私はDNA損傷後、クロマチンからChk1が解離するため、ヒストンH3-T11のリン酸化が急速に減少し、サイクリンやCdkなど増殖関連遺伝子の転写が抑制されることを見出した。哺乳類の細胞周期静止期の維持において、増殖関連遺伝子の転写を抑制する機構においても同様にChk1を介したヒストン修飾が関与している可能性を示した。

Research Products

• [Journal Article] Cyclin A-Cdk1 regulates the origin firing program in mammalian cells (2009)
  • Author(s): Katsuno Y, Suzuki A, Sugimura K, Okumura K, Zineldeen DH, Shimada M, Niida H, Mizuno T, Hanaoka F and Nakanishi M
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A. 106 Pages: 3184-3189
  • Peer Reviewed
• [Journal Article] Ptpcd-1 is a novel cell cycle related phosphatase that regulates centriole duplication and cytokinesis (2009)
  • Author(s): Zineldeen DH, Shimada M, Niida H, Katsuno Y and Nakanishi M
  • Journal Title: Biochem. Biophys. Res. Commun. 380 Pages: 460-466
  • Peer Reviewed
• [Journal Article] チェックポイントキナーゼChk1による転写制御とストレス応答 (2009)
  • Author(s): 中西真、島田緑
  • Journal Title: 細胞工学 28 Pages: 22-26
• [Journal Article] Chk1 is a histone H3-T11 kinase that regulates DNA damage-induced transcriptional repression (2008)
  • Author(s): Shimada M, Niida H, Zineldeen DH, Tagami H, Tanaka M, Saito H and Nakanishi M
  • Journal Title: Cell 132 Pages: 221-232
  • Peer Reviewed
• [Journal Article] Cdc2p controls the forkhead transcription factor Fkh2p by phosphorylation during sexual differentiation in fission yeast (2008)
  • Author(s): Shimada M, Yamada-Namikawa C, Murakami-Tonami Y, Yoshida T, Nakanishi M, Urano T and Murakami H
  • Journal Title: The EMBO Journal 27 Pages: 132-142
  • Peer Reviewed
• [Journal Article] Essential role of Chk1 in Sphase progression through regulation of RNR2 expression Biochem (2008)
  • Author(s): Naruyama H, Shimada M, Niida H, Zineldeen DH, Hashimoto Y, Kohri K and Nakanishi M
  • Journal Title: Biophys. Res. Commun 374 Pages: 79-83
  • Peer Reviewed
• [Journal Article] Checkpoint meets transcription at a novel milestone (H3-T11) (2008)
  • Author(s): Shimada M and Nakanishi M
  • Journal Title: Cell Cycle 7 Pages: 1555-1559
  • Peer Reviewed
• [Journal Article] DNA損傷反応とクロマチン修飾 (2008)
  • Author(s): 島田緑、中西真
  • Journal Title: 細胞工学 27 Pages: 1162-1167
  • NAID: 40016310561
• [Journal Article] Chk1の新しい機能-ヒストンH3-Thr11のリン酸化を介した転写制御機構 (2008)
  • Author(s): 島田緑、中西真
  • Journal Title: 実験医学 26 Pages: 1740-1743
• [Journal Article] Chkl is a histone 113-T11 kinase that regulates DNA damage-induced transcriptional renression (2008)
  • Author(s): Midori Shimada
  • Journal Title: Cell 132 Pages: 221-232
  • Peer Reviewed
• [Journal Article] Cdc2p controls the forkhead transcription factor Fkh9p by phosp horylation during sexual differentiation in fission yeast (2008)
  • Author(s): Midori Shimada
  • Journal Title: The EMBO Journal 27 Pages: 132-142
  • Peer Reviewed
• [Journal Article] Checkpoint meets transcription at a novel milestone (H3-T11) (2008)
  • Author(s): Midori Shimada
  • Journal Title: Cell Cycle 7 Pages: 1555-1559
  • Peer Reviewed
• [Journal Article] Chkl is a histone H3 Threonine 11 kinase that regulates DNA damage-induced transcriptional repression (2008)
  • Author(s): Midori Shimada, et. al.
  • Journal Title: Cell 132 Pages: 221-232
  • Peer Reviewed
• [Journal Article] Cdc2p controls the forkhead transcription factor Fkh2p by phosphorylati on during sexual differentiation in fission yeast (2008)
  • Author(s): Midori Shimada, et. al.
  • Journal Title: The EMBO Journal 27 Pages: 132-142
  • Peer Reviewed
• [Presentation] DNA damage-induced transcriptional repression through histone H3-Thr11 dephosphorylation (2009)
  • Author(s): Shimada M
  • Organizer: Chromatin meeting
  • Place of Presentation: Singapore
  • Year and Date: 2009-02-10
• [Presentation] The role of phosphorylation of H3-Threonine 11 in transcriptional regulation and cellular senescence (2008)
  • Author(s): 島田緑
  • Organizer: 第9回がん若手ワークショップ
  • Place of Presentation: 蓼科
  • Year and Date: 2008-09-05
• [Presentation] Checkpoints meet transcription at a novel milestone (2008)
  • Author(s): Shimada M
  • Organizer: International Symposium on Chromosome Dynamics
  • Place of Presentation: Ise, Japan
  • Year and Date: 2008-05-28
• [Presentation] Checkpoints meet transcription at a novel milestone. Internation al Symposium on Chromosome Dynamics (2008)
  • Author(s): Midori Shimada
  • Organizer: International Symposium on Chromosome Dynamics
  • Place of Presentation: ホテル近鉄アクアヴィラ伊勢志摩
  • Year and Date: 2008-05-28
• [Presentation] DNA damage-induced transcriptional repression through histone H3-Thr11 dephosphorylation (2008)
  • Author(s): Shimada M
  • Organizer: Gordon Research Conferences, Chromatin structure and function
  • Place of Presentation: Lucca, Italy
  • Year and Date: 2008-05-11
• [Presentation] Chk1に依存したヒストンH3-T11のリン酸化の減少がDNA損傷後の転写抑制を引き起こす (2008)
  • Author(s): 島田緑
  • Organizer: 第25回染色体ワークショップ
  • Place of Presentation: 湯河原
  • Year and Date: 2008-01-30
• [Presentation] Chk1に依存したヒストンH3-T11のリン酸化の減少がDNA損傷後の転写抑制を引き起こす (2007)
  • Author(s): 島田緑
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] Chk1に依存したピストンH3-T11のリン酸化の減少がDNA損傷後の転写抑制を引き起こす (2007)
  • Author(s): 島田 緑
  • Organizer: 第30回目本分子生物学会年会 第80回日本生化学会大会 合同大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-12
• [Book] DNA損傷反応とクロマチン修飾 (2008)
  • Author(s): 島田緑
  • Total Pages: 6
  • Publisher: 秀潤社
• [Remarks]
  • URL: http://www.med.nagoya-cu.ac.jp/w3med/research/reports/results/001.html