Unraveling the regulation of fidelity in DNA replication and homology-directed repair

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03186
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: Kyushu University
• Principal Investigator: Takahashi Tatsuro 九州大学, 理学研究院, 教授 (50452420)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: ミスマッチ修復 / ツメガエル卵抽出液 / 相同組換え / ゲノム安定性 / DNA二重鎖切断修復

Outline of Final Research Achievements

The mismatch repair system handles both DNA biosynthesis and recombination errors to increase the fidelity in DNA replication and recombination. While these reactions are triggered by the same mismatch sensors, the downstream events are highly diverged. Importantly, the molecular mechanism of recombination regulation by the mismatch repair system remains ambiguous, and the pathway-choice mechanism of the two pathways is also poorly understood. In this study, we established biochemical model systems that recapitulate the regulation of recombination using Xenopus egg nucleoplasmic extracts and purified proteins. Using these systems, we identified factors that affect the fidelity of recombination. These results contribute to the basic understanding of genome maintenance.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

ゲノムの安定性は、がんなどのゲノム安定性疾患や、老化の背景として重要である。本研究で取り扱うミスマッチ応答機構は重要ながん抑制機構として知られ、この機構の破綻は孤発性および遺伝性発がんの原因のひとつとなっている。本研究の成果は、ミスマッチ応答機構の動作原理の理解を進めるもので、基礎科学としてのゲノム安定性、ゲノム品質管理の理解に貢献する。また、本研究成果は、ゲノム安定性維持機構の解明を通じて、発がんや老化の理解にも貢献する。