Reguratory mechanisms of radiation sensitivity by molecules expressed in epigenetics-dependent manners

• Project/Area Number: 24390289
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: The University of Tokyo
• Principal Investigator: MIYAGAWA Kiyoshi 東京大学, 医学(系)研究科(研究院), 教授 (40200133)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2013: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2012: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: 放射線治療生物学 / エピジェネティクス

Outline of Final Research Achievements

To explore the possibility that molecules expressed in somatic cells in epigenetics-dependent manners affect the machinery responding to DNA damage induced by radiation and others, we investigated roles of meiosis-specific molecules in somatic cells. Our studies revealed that the meiosis-specific protein SYCE1 is expressed in some types of cancers and induces tolerance to radiation by promoting DNA double-strand break repair mediated by homologous recombinational repair and by nonhomologous end-joining through activation of the genome damage response.

Research Products

• [Journal Article] Targeting DNA damage response in cancer therapy. (2014)
  • Author(s): Hosoya N, Miyagawa K
  • Journal Title: Cancer Sci. Volume: 105 Issue: 4 Pages: 370-388
  • DOI: 10.1111/cas.12366
  • Peer Reviewed / Open Access
• [Journal Article] Rad54B serves as a scaffold in the DNA damage response that limits checkpoint strength (2014)
  • Author(s): Takaaki Yasuhara, Takahiko Suzuki, Mari Katsura, Kiyoshi Miyagawa
  • Journal Title: Nature Communications Volume: 5 Issue: 1 Pages: 5426-5426
  • DOI: 10.1038/ncomms6426
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Comparison of the bromodeoxyuridine-mediated sensitization effects between low-LET and high-LET ionizing radiation on DNA double-strand breaks (2013)
  • Author(s): Fujii Y, Genet MD, Roybal EJ, Kubota N, Okayasu R, Fujimori A, Mori T, Mauro K, Kato TA
  • Journal Title: Oncol Rep Volume: 29 Issue: 6 Pages: 2133-2139
  • DOI: 10.3892/or.2013.2354
  • Peer Reviewed
• [Journal Article] The HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin modulates radiosensitivity by downregulating serine/threonine kinase 38 via Sp1 inhibition (2013)
  • Author(s): Atsushi Enomoto
  • Journal Title: European Journal of Cancer Volume: 48 Issue: 16 Pages: 3547-3558
  • DOI: 10.1016/j.ejca.2013.06.034
  • Peer Reviewed
• [Journal Article] Hyperthermia inhibits homologous recombination repair and sensitizes Cells to ionizing radiation in a time- and temperature-dependent manner (2013)
  • Author(s): Genet sc
  • Journal Title: J Cell Physiol Volume: 228 Issue: 7 Pages: 1473-1481
  • DOI: 10.1002/jcp.24302
  • Peer Reviewed
• [Presentation] がんにおける非遺伝子変異的プロセスによるDNA損傷応答シグナルの制御機構 (2014)
  • Author(s): 細谷紀子、宮川清
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市）
  • Year and Date: 2014-11-27
• [Presentation] The cancer-testis antigen SYCE2 promotes DNA double-strand break repair through activation of ATM (2014)
  • Author(s): Noriko Hosoya, Kiyoshi Miyagawa
  • Organizer: 第73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: 2014-09-27
• [Presentation] The role for a meiosis-specific protein in regulating DNA damage response and chromosome stability in cancer (2012)
  • Author(s): 細谷紀子
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌市教育文化会館(北海道)
  • Year and Date: 2012-09-19
• [Presentation] DNA repair and cancer therapy
  • Author(s): Kiyoshi Miyagawa
  • Organizer: The 3rd Asian Congress of Radiation Research
  • Place of Presentation: Beijing International Convention Center, Beijing, China
  • Invited