Molecular mechanism of epigenetic memory associated with DNA damage response

• Project/Area Number: 26281023
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Nagasaki University
• Principal Investigator: SUZUKI Keiji 長崎大学, 原爆後障害医療研究所, 准教授 (00196809)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2015: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2014: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
• Keywords: 放射線 / DNA損傷 / 情報伝達 / エピジェネティクス / DNA損傷応答 / 分裂期 / ヒストン

Outline of Final Research Achievements

DNA double-strand breaks caused by ionizing radiation result in an activation of ATM-dependent DNA damage signaling pathway. While most of DNA breaks are amendable, unreparable and residual breaks amplify DNA damage signal, which will be transmitted through mitosis. In the present study, it was aimed to identify epigenetic marks associated with DNA damage signal transmission. Analyses using immunofluorescence revealed that histone modifications, such as methylation, acetylation, and ubiquitination, might not be involved in the process, whereas phosphorylation of histone H2AX remained on damaged chromosomes. In addition, localization of MDC1 on damaged chromosomes was detected during mitosis. These results indicate that epigenetic modification of H2AX is critical for the transmission of amplified DNA damage signal through cell division.

Research Products

• [Journal Article] Regulation of pairing between broken DNA-containing chromatin regions by Ku80, DNA-PKcs, ATM, and 53BP1 (2017)
  • Author(s): Motohiro Yamauchi, Atsushi Shibata, Keiji Suzuki, Masatoshi Suzuki, Atsuko Niimi, Hisayoshi Kondo, Miwa Miura, Miyako Hirakawa, Keiko Tsujita, Shunichi Yamashita, Naoki Matsuda
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 41812-41812
  • DOI: 10.1038/srep41812
  • NAID: 120006987560
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Unstable chromosome aberrations do not accumulate in normal fibroblast after fractionated x-irradiation. (2015)
  • Author(s): Ojima M, Ito M, Suzuki K, Kai M
  • Journal Title: PLoS One Volume: 10(2) Issue: 2 Pages: e0116645-e0116645
  • DOI: 10.1371/journal.pone.0116645
  • Peer Reviewed / Open Access
• [Presentation] ATM and DNA-PKcs suppress pairing between multiple DNA double-strand breaks (2015)
  • Author(s): Motohiro Tayamuchi, Keiji Suzuki,
  • Organizer: BMB2015
  • Place of Presentation: 神戸国際展示場（兵庫県・神戸市）
  • Year and Date: 2015-12-03
• [Remarks] 長崎大学原爆後障害医療研究所
  • URL: http://www-sdc.med.nagasaki-u.ac.jp/index-sjis.html