DNA polymerase dynamics and genome stability

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03233
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43050:Genome biology-related
• Research Institution: Japanese Foundation for Cancer Research (2022); Tohoku University (2020-2021)
• Principal Investigator: DAIGAKU Yasukazu 公益財団法人がん研究会, がん研究所 がんゲノム動態プロジェクト, プロジェクトリーダー (80619875)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: DNA複製 / 突然変異 / DNAポリメラーゼ

Outline of Final Research Achievements

There are 15 different DNA polymerases in eukaryotes and the fidelity and efficiency of their synthetic activities are distinct. The correct division of labour among these polymerases is therefore a primary factor in determining the stability of genome duplication. Among these DNA polymerases, polymerase ζ (Polζ) was previously identified to be the main cause of spontaneous mutagenesis and share subunits with Polymerase δ (Polδ), which is responsible for lagging strand DNA synthesis. In this study, we investigated how the function of Polζ is regulated by subunits of Polδ. We discovered that, in the content of DNA damage tolerance, the abundance of Cdc1 (one of the Polδ subunits) is the key factor to activate Polζ. We also observed that the relative amount of Cdc1 to the Polδ catalytic subunit Cdc6 are increased in G2 phase. This trend in the protein level of Cdc1 may lead to high Polζ activity in G2 phase and mutagenesis by this polymerase.

Free Research Field

分子遺伝学

Academic Significance and Societal Importance of the Research Achievements

本研究は、分裂酵母を中心的に使用し、突然変異の主な原因となるポリメラーゼの制御を明らかにすることを目的とした。今後、哺乳類細胞を対象とした研究へと発展させることにより、がん細胞における突然変異率の上昇の原因究明に貢献することが大いに期待される。また、この研究をモデルとして、その他の多くのDNAポリメラーゼを対象に加えた研究へと発展させ、多種多様なDNAポリメラーゼが協調的に機能する仕組みが明らかになると期待される。