Molecular mechanism of epigenetic memory associated with DNA damage response

2016 Fiscal Year Final Research Report

• 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
• Keywords: 放射線 / DNA損傷 / 情報伝達 / エピジェネティクス

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.

Free Research Field

放射線生物学