Regulation of asymmetric cell division by the machinery maintaining genome stability

• Project/Area Number: 15K14376
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: The University of Tokyo
• Principal Investigator: MIYAGAWA KIYOSHI 東京大学, 大学院医学系研究科(医学部), 教授 (40200133)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 細胞周期 / 不均等細胞分裂

Outline of Final Research Achievements

To clarify the molecular mechanism underlying the nature of cancer stem cells characterized by tolerance to cancer treatment, we tried to identify the machinery regulating both the DNA double-strand break response and asymmetric cell division. We found that Rad54B, which repairs double-strand breaks by homologous recombination and regulates cell-cycle checkpoint by degrading p53, promotes asymmetric cell division in the neuroblastoma-derived cell line. Furthermore, we found that Rad54B activates the Notch-signaling pathway by inhibiting Numb, which may be involved in asymmetric cell division.

Research Products

• [Journal Article] Extremotolerant tardigrade genome and improved radiotolerance of human cultured cells by tardigrade-unique protein. (2016)
  • Author(s): Hashimoto T, Horikawa DD, Saito Y, Kuwahara H, Kozuka-Hata H, Shin-I T, Minakuchi Y, Ohishi K, Motoyama A, Aizu T, Enomoto A, Kondo K, Tanaka S, Hara Y, Koshikawa S, Sagara H, Miura T, Yokobori S, Miyagawa K, Suzuki Y, Kubo T, Oyama M, Kohara Y, Fujiyama A, Arakawa K, Katayama T, Toyoda A and Kunieda T
  • Journal Title: Nature Communications Volume: 7 Issue: 1 Pages: 12808-12808
  • DOI: 10.1038/ncomms12808
  • NAID: 120005971035
  • Peer Reviewed / Open Access
• [Journal Article] High RAD54B expression: an independent predictor of postoperative distant recurrence in colorectal cancer patients. (2015)
  • Author(s): Nagai Y, Yamamoto Y, Yasuhara T, Hata K, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, Nozawa H, Kazama S, Yamaguchi H, Ishihara S, Sunami E, Yamanaka T, Miyagawa K, Watanabe T.
  • Journal Title: Oncotarget Volume: 6 Issue: 25 Pages: 21064-21073
  • DOI: 10.18632/oncotarget.4222
  • Peer Reviewed / Open Access
• [Presentation] The Rad54B-p53 axis limits the strength of DNA damage checkpoint (2016)
  • Author(s): Takaaki Yasuhara, Kiyoshi Miyagawa
  • Organizer: 日本放射線影響学会第59回大会
  • Place of Presentation: JMSアステールプラザ（広島県広島市）
  • Year and Date: 2016-10-26
• [Presentation] The Rad54B-p53 axis limits the strength of DNA damage checkpoint (2016)
  • Author(s): Takaaki Yasuhara, Kiyoshi Miyagawa
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-10-06
• [Presentation] The novel mechanism linking cell cycle regulation to cancer development (2015)
  • Author(s): Yasuhara, Takahiko Suzuki, Mari Katsura, Kiyoshi Miyagawa
  • Organizer: Gordon Research Seminar & Caoference - Cell Growth & Proliferation
  • Place of Presentation: Vermont（米国）
  • Year and Date: 2015-07-11
  • Int'l Joint Research
• [Presentation] Rad54B serves as a scaffold in the DNA damage response that limits checkpoint strength (2015)
  • Author(s): Takaaki Yasuhara, Takahiko Suzuki, Mari Katsura, Kiyoshi Miyagawa
  • Organizer: 15th International Congress of Radiation Research
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2015-05-25
  • Int'l Joint Research