Functional analysis of molecular basis of nucleotide excision repair against DNA lesions in high-dimensional chromatin

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K18034
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 63030:Chemical substance influence on environment-related
• Research Institution: The University of Tokyo
• Principal Investigator: Matsumoto Syota 東京大学, 定量生命科学研究所, 助教 (10880643)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: DNA修復 / クロマチン / ヌクレオチド除去修復 / ヌクレオソーム / NER

Outline of Final Research Achievements

In this research, we aimed to reveal the molecular mechanism of nucleotide excision repair (NER), one of the important DNA repair mechanism to eliminate wide variety of DNA lesions. Especially, our genome forms DNA-protein complex called “chromatin,” which limits the access of DNA repair protein to DNA lesions.
In this research, we figured out the molecular mechanism of DNA repair protein targeting DNA lesions in nucleosomes, a basic unit of chromatin. In these results, we revealed that binding affinity and efficiency of damage recognition are depending on the location of DNA lesions and these were not observed on naked DNA.

Free Research Field

DNA修復

Academic Significance and Societal Importance of the Research Achievements

本研究は細胞内におけるDNA修復機構を分子レベルで調べたものであり、これまで未知の領域であったクロマチン上のDNA修復という観点で研究を進めてきた。これらクロマチン上におけるDNA修復研究は、DNA修復異常疾患を持つ患者の治療法の確立や臨床医療への応用へと繋げていく上で必須であり、幅広い患者の治療へと貢献する可能性を秘めている点で社会的意義は大きいと考えている。