Regulation of radiation sensitivity by a pathway linking DNA repair with cell-cycle control

• Project/Area Number: 15H04902
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Radiation science
• 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 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: 放射線治療生物学 / 放射線感受性

Outline of Final Research Achievements

To understand mechanisms that affect radiation sensitivity by linking DNA repair with cell-cycle control, we investigated a role of Rad54B, the protein involved in homologous recombination and p53-mediated G1/S checkpoints, in G0/G1 progression. Our studies revealed that Rad54B promotes expression of cyclin D1 by forming an autonomous regulatory loop with E2F1 and c-Jun and defines timing of the exit from quiescence.

Research Products

• [Journal Article] Bisdemethoxycurcumin enhances X-ray-induced apoptosis possibly through p53/Bcl-2 pathway. (2017)
  • Author(s): A. Enomoto, J. Yamada, A. Morita, and K. Miyagawa.
  • Journal Title: Mutat. Res. Volume: 815 Pages: 1-5
  • DOI: 10.1016/j.mrgentox.2016.12.005
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells (2017)
  • Author(s): Sato Hiro、Niimi Atsuko、Yasuhara Takaaki、Permata Tiara Bunga Mayang、Hagiwara Yoshihiko、Isono Mayu、Nuryadi Endang、Sekine Ryota、Oike Takahiro、Kakoti Sangeeta、Yoshimoto Yuya、Held Kathryn D.、Suzuki Yoshiyuki、Kono Koji、Miyagawa Kiyoshi、Nakano Takashi、Shibata Atsushi
  • Journal Title: Nature Communications Volume: 8 Issue: 1 Pages: 1751-1751
  • DOI: 10.1038/s41467-017-01883-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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] Oncogenic and anti-oncogenic properties of RAD54B in the DNA damage response (2017)
  • Author(s): Kiyoshi Miyagawa
  • Organizer: 1st International Symposium on Radiation Therapeutics & Biology
  • Int'l Joint Research / Invited
• [Presentation] Regulation of checkpoint strength in the DNA damage response (2017)
  • Author(s): Kiyoshi Miyagawa, Takaaki Yasuhara
  • Organizer: 33rd International Symposium of Radiation Biology Center, Kyoto University
  • Int'l Joint Research / Invited
• [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): Takaaki Yasuhara, Takahiko Suzuki, Mari Katsura, Kiyoshi Miyagawa
  • Organizer: Gordon Research Seminar & Conference - 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