Analysis of GRWD1, a novel histone-binding protein involved in chromosomal replication initiation and segregation

• Project/Area Number: 21370084
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Kyushu University (2010-2011); National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East (2009)
• Principal Investigator: FUJITA Masatoshi 九州大学, 薬学研究院, 教授 (30270713)
• Co-Investigator(Kenkyū-buntansha): WAGA Shou 日本女子大学, 理学部, 教授 (60222402)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000); Fiscal Year 2011: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2010: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2009: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: GRWD1 / Cdt1 / 複製開始複合体 / 細胞周期 / ヒストンシャペロ / MCM / クロマチン / 次世代シークエンシング / 複製開始制御 / ヒストンシャペロン / ライセンシング制御 / 複製開始点

Research Abstract

Precise regulation of DNA replication reaction is essential for integrity of genome information. Cdt1, together with ORC and CDC6, loads MCM replication helicase complex onto DNA replication origin. GRWD1 has been identified as a novel Cdt1-binding protein. In this research project, we have obtained following findings.(GRWD1 binds to Cdc6 and Cdt1, thereby accumulates onto replication origins.(2) GRWD1is a novel histone-binding protein and has a histone chaperon activity. Furthermore, GRWD1is actually involvedin regulation of chromatin openness(in general, it is believed that open chromatin structure promotes various transactions on chromatin).(3) GRWD1 silencing by siRNA inhibits MCM loading. Therefore, GRWD1may play a crucial role in regulation ofreplication.

Research Products

• [Journal Article] The E1 protein of human papillomavirus type 16 is dispensable for maintenance replication of the viral genome. (2012)
  • Author(s): Egawa, N., et al
  • Journal Title: J. Virol. Volume: 86 Pages: 3276-3281
  • DOI: 10.1128/jvi.06450-11
  • Peer Reviewed
• [Journal Article] Chromatin remodeler Sucrose Non-Fermenting 2Homolog(SNF2H) is recruited onto DNAreplication origins through interaction with Cdc10 protein-dependent transcript 1(Cdt1) and promotes pre-replication complex formation (2011)
  • Author(s): Sugimoto, N., Yugawa, T., Iizuka, M., Kiyono, T. & Fujita, M.
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 39200-39210
• [Journal Article] The chromatin remodeler sucrose nonfermenting 2 homologue (SNF2H) is recruited onto DNA replication origins through interaction with cdc-10 dependent transcript (CDT1) and promotes the pre-replication complex formation (2011)
  • Author(s): Nozomi Sugimoto
  • Journal Title: J Biol Chem Volume: 286 Pages: 39200-10
  • DOI: 10.1074/jbc.m111.256123
  • Peer Reviewed
• [Journal Article] An in vitro multistep carcinogenesis model for both HPV-positive and -negative human oral squamous cell carcinoma (2011)
  • Author(s): Zushi, Y., et al
  • Journal Title: Am.J.Cancer Res. Volume: 1 Pages: 869-881
  • Peer Reviewed
• [Journal Article] CDC6interaction with ATR regulates activation ofa replication checkpoint in higher eukaryotic cells (2010)
  • Author(s): Yoshida, K., Sugimoto, N., Iwahori, S., Yugawa, T., Narisawa-Saito, M., Kiyono, T. & Fujita
  • Journal Title: J. Cell Sci Volume: 123 Pages: 225-235
• [Journal Article] CDC6 interaction with ATR regulates activation of a replication checkpoint in higher eukaryotic cells (2010)
  • Author(s): Kazumasa Yoshida
  • Journal Title: J.Cell Sci Volume: 123 Pages: 225-235
  • Peer Reviewed
• [Journal Article] CDC6 interaction with ATR regulates activation of a replication checkpoint in higher eukaryotic cells (2010)
  • Author(s): Kazumasa Yoshida
  • Journal Title: J.Cell Sci 123 Pages: 225-235
  • Peer Reviewed
• [Journal Article] Redundant and differential regulation of multiple licensing factors ensures prevention of rereplication in normal human cells (2009)
  • Author(s): Sugimoto, N., Yoshida, K., Tatsumi, Y., Yugawa, T., Narisawa-Saito, M., Waga, S., Kiyono, T. & Fujita, M.
  • Journal Title: J. Cell Sci Volume: 122 Pages: 1184-1191
• [Journal Article] Redundant and differential regulation of multiple licensing factors ensures prevention of rereplication in normal human cells (2009)
  • Author(s): Nozomi Sugimoto
  • Journal Title: J.Cell Sci 122 Pages: 1184-1191
  • Peer Reviewed
• [Journal Article] Histone acetyltransferase Hbo1 : catalytic activity, cellular abundance, and links to primary cancers (2009)
  • Author(s): Masayoshi Iizuka
  • Journal Title: Gene 436 Pages: 108-114
  • Peer Reviewed
• [Presentation] The Cdt1-binding protein GRWD1 is a novel histone chaperone involved in replication licensing. (2011)
  • Author(s): Sugimoto, N., Yasukouchi, S., Watanabe, S., Kiyono, T., Kurumizaka, H. & Fujita, M.
  • Organizer: 第34回日本分子生物学会年会ワークショップ
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-12-16
• [Presentation] The Cdt1-binding protein GRWD1 is a novel histone chaperone involved in replication licensing (2011)
  • Author(s): Nozomi Sugimoto, et al
  • Organizer: 第34回日本分子生物学会年会ワークショップ
  • Place of Presentation: パシフィコ横浜(招待講演)
  • Year and Date: 2011-12-16
• [Presentation] A novel function of ATM during the unperturbed S phase : Regulation of Cdt1 proteolysis and prevention of rereplication (2011)
  • Author(s): Satoko Iwahori, et al
  • Organizer: Cold Spring Harbor Laboratory 2011 Meeting on Eukaryotic DNA Replication & Genome Maintenance
  • Place of Presentation: Cold Spring Harbor, NY, USA
  • Year and Date: 2011-09-07
• [Presentation] A novel function of ATM : regulation of Cdt1 during the S phase (2010)
  • Author(s): Masatoshi Fujita
  • Organizer: Biochemistry and Molecular Biology 2010, Symposium
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-10
• [Presentation] A chromatin remodeler SNF2H promotes pre-RC formation via Cdt1 interaction (2010)
  • Author(s): Nozomi Sugimoto
  • Organizer: Biochemistry and Molecular Biology 2010
  • Place of Presentation: 神戸ポートアイランド(一般口頭発表)
  • Year and Date: 2010-12-07
• [Presentation] 複製開始複合体形成に関与しているCdt1結合性ヒストン制御蛋白質 (2010)
  • Author(s): 藤田雅俊
  • Organizer: 大阪大学蛋白質研究所セミナー「ゲノム機能の記憶の成立機序とその制御」
  • Place of Presentation: 大阪大学蛋白質研究所
  • Year and Date: 2010-11-19
• [Presentation] CDC6 interaction with ATR regulates activation of a replication checkpoint in higher eukaryotic cells (2009)
  • Author(s): Kazumasa Yoshida
  • Organizer: Keystone Symposia "Telomere Biology and DNA Repair"
  • Place of Presentation: Ashmore, Queensland, Australia
  • Year and Date: 2009-10-12
• [Presentation] A chromatin remodeler SNF2H is involved in pre-RC formation and Cdt1-induced checkpoint activation (2009)
  • Author(s): Nozomi Sugimoto
  • Organizer: Keystone Symposia "Telomere Biology and DNA Repair"
  • Place of Presentation: Ashmore, Queensland, Australia
  • Year and Date: 2009-10-12
• [Presentation] 正確にゲノムを倍加させる:複製開始因子Cdt1の分解制御機構の解明と抗がん剤開発への応用 (2009)
  • Author(s): 藤田雅俊
  • Organizer: 福井大学大学院工学研究科、招請研究セミナー
  • Place of Presentation: 福井
  • Year and Date: 2009-05-26
• [Presentation] A chromatin remodeler SNF2H is involved in pre-RC formation and Cdt1-induced checkpoint activation (2009)
  • Author(s): Sugimoto, N., Waga, S., Kiyono, T. & Fujita, M.
  • Organizer: Keystone Symposia "Telomere Biology and DNA Repair"
  • Place of Presentation: Ashmore, Queensland, Australia
• [Presentation] CDC6 interaction with ATR regulates activation of a replication checkpoint in higher eukaryotic cells (2009)
  • Author(s): Yoshida, K., Iwahori, S., Kiyono, T. & Fujita, M.
  • Organizer: Keystone Symposia"Telomere Biology and DNA Repair"
  • Place of Presentation: Ashmore, Queensland, Australia
• [Remarks] ホームページ:
  • URL: http://tansaku.phar.kyushu-u.ac.jp/saito/top.html
• [Remarks] 九州大学薬学研究院公開講座:遺伝情報を過不足無く受け継ぐためのしくみ?分子生物学的解明と医薬研究への応用?」平成22年9月26日、九州大学
• [Remarks]
  • URL: http://tansaku.phar.kyushu-u.ac.jp/saito/top.html
• [Remarks]
  • URL: http://tansaku.phar.kyushu-u.ac.jp/saito/top.html
• [Patent(Industrial Property Rights)] G2/M期停止及び細胞死を誘導するベンゾヒドラジド誘導体 (2011)
  • Inventor(s): 藤田雅俊、大嶋孝志、森本浩之
  • Industrial Property Rights Holder: 九州大学
  • Industrial Property Number: 2011-234309
  • Filing Date: 2011-10-25