Investigation of the mechanism underlying the association between DSB repair and Transcription

• Project/Area Number: 17K19615
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology and related fields
• Research Institution: Tokyo University of Technology
• Principal Investigator: UI Ayako 東京工科大学, 応用生物学部, 准教授 (00469967)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: ＤＮＡ修復 / DSB修復 / 転写 / がん

Outline of Final Research Achievements

DSB (DNA double strand break) is one of harmful DNA damage that induces cancer. Recently, DSB-induces transcriptional repression prevents genome instability and cancer. In this study, we investigated the relationship between DSB-induced transcriptional repression, DSB repair and transcription. We found that factors of histone ubiquitination which have been reported to be involved in transcription and DSB repair are required for DSB-induced transcriptional repression. In addition, we identify the histone modifications that are required for DSB-induced transcriptional repression. These findings may be an important information to reveal the mechanism of genome instability and cancer.

Academic Significance and Societal Importance of the Research Achievements

近年、ＤＳＢ依存的に起こる転写抑制は、ゲノム安定性維持と細胞がん化の抑制に重要な役割を果たすことが明らかになってきている。そこで本研究の成果は、ゲノム安定性維持のメカニズムの解明による細胞がん化機構の解明につながると考えられる。

Research Products

• [Journal Article] Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites (2018)
  • Author(s): Yasuda Takeshi、Kagawa Wataru、Tajima Katsushi
  • Journal Title: PLOS Genetics Volume: 14 Issue: 3 Pages: 1007277-1007277
  • DOI: 10.1371/journal.pgen.1007277
  • NAID: 120006459820
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Phosphorylated HBO1 at UV irradiated sites is essential for nucleotide excision repair (2017)
  • Author(s): Niida, H., Matsunuma, R., Horiguchi, R., Uchida, C., Nakazawa, Y., Motegi, A., Nishimoto, K., Sakai, S., Ohhata, T., Kitagawa, K., Moriwaki, S., Nishitani, H., Ui, A., Ogi, T. and Kitagawa, M.
  • Journal Title: Nature Communications Volume: 8 Issue: 1 Pages: 16102-16102
  • DOI: 10.1038/ncomms16102
  • Peer Reviewed / Open Access
• [Journal Article] Nucleosome remodelling, DNA repair and transcriptional regulation build negative feedback loops in cancer and cellular ageing (2017)
  • Author(s): Watanabe Reiko、Kanno Shin-ichiro、Mohammadi Roushandeh Amaneh、Ui Ayako、Yasui Akira
  • Journal Title: Philos Trans R Soc Lond B Biol Sci Volume: 372 Issue: 1731 Pages: 0473-0473
  • DOI: 10.1098/rstb.2016.0473
  • Peer Reviewed / Int'l Joint Research
• [Presentation] DSB修復におけるヒストンメチル化H3K4の機能 (2018)
  • Author(s): 宇井彩子
  • Organizer: 日本遺伝学会 ワークショップ
  • Invited
• [Presentation] DSBシグナル伝達と修復におけるヒストン修飾因子とクロマチンリモデリング複合体の機能解析 (2018)
  • Author(s): 宇井彩子
  • Organizer: 日本放射線影響学会 シンポジウム
  • Invited
• [Presentation] DSBシグナル伝達と修復におけるPRC1とヒストンユビキチン化に関する分子機能解析 (2018)
  • Author(s): 宇井彩子
  • Organizer: 日本分子生物学会 ワークショップ
  • Invited
• [Presentation] ゲノム安定性におけるDSB修復と蛋白質恒常性維持機構の共役 (2017)
  • Author(s): 宇井彩子
  • Organizer: DNA損傷応答ワークショップ