Elucidation of the molecular mechanism of male infertility caused by disruption of genome stability maintenance mechanism

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07053
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Azabu University (2021); Tokyo University of Pharmacy and Life Science (2019-2020)
• Principal Investigator: Matsushita Nobuko 麻布大学, 生命・環境科学部, 教授 (30333222)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: DNA損傷修復 / エピゲノム

Outline of Final Research Achievements

In this study, I aimed to elucidate the molecular mechanism of DNA damage repair responses by reconstructing epigenomic information and to elucidate the regulatory mechanism of DNA damage-responsive genes by epigenetic regulators. As a result, I identified epigenetic regulators whose transcriptional activity was altered by DNA damage induced by irradiation or anticancer drugs. In addition, I created a reporter construct in which the promoter region of the epigenomic regulator was introduced upstream of the luciferase gene and performed a luciferase-based reporter assay. Therefore, I identified compounds that inhibit this epigenetic factor and regulate DNA damage repair.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

加齢や放射線などの環境要因によるゲノムDNA損傷の蓄積が、細胞にエピジェネティックな変化をもたらし、がんの発症や老化を促進することが報告され始め、DNA損傷修復とエピジェネティックスの関連の解明は生命科学の重要な課題に浮上している。本研究の目的は、エピゲノム制御因子によるDNA損傷修復応答制御機構を明らかにすることであり、DNA損傷後にどのようなメカニズムによってエピゲノム制御因子の転写が活性化され、ヒストン修飾を行い、DNA損傷修復応答の指標として機能するのか、エピゲノム情報の再構築によるDNA損傷修復反応の分子基盤を明らかにすることは癌の発症のメカニズムの解明に有用である。