Analysis of minor double-strand DNA break repair mechanisms in the maintenance of genomic stability in human cells.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15069
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43050:Genome biology-related
• Research Institution: Yokohama City University
• Principal Investigator: SAITO SHINTA 横浜市立大学, 理学部, 助教 (60837897)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: DNA修復 / 組換え / 二本鎖切断 / Alu

Outline of Final Research Achievements

In this study, I performed structure-function relationship analysis of DNA polymerase θ (Polθ) , which is essential for alt-EJ. In a series of experiments, I found that in addition to the ATPase and polymerase domains, three unique insertion loops of Polθ also play important functions in alt-EJ. I also identified several novel factors involved in Alu-Alu recombination through various genetic analyses. These findings are expected to provide significant insights into the understanding of the mechanism of DNA double-strand break repair and potentially for medical applications in the field of drug discovery.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

二本鎖DNA切断は最も危険なDNA損傷であり、不完全な修復はがん化や細胞死を引き起こす。そのため、二本鎖DNA切断が細胞内でどのように修復されるのかを理解することは、ゲノム安定性維持機構の具体像やがん化との関連についての正確な理解に役立つだけでなく、放射線や抗がん剤を用いたがん治療に重要な示唆を与える。本研究ではDSB修復経路であるalt-EJおよびAlu-Alu組換え（SSA）の分子機構の一旦を明らかにすることができた。これらの結果は、DSB修復機構の全容解明のみならず創薬医療分野への応用（特に抗がん剤開発）に向けて重要な示唆を与えると期待される。