Molecular mechanisms of transcription-coupled repair (TCR) and pathogenesis of TCR-deficient human genetic disorders

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02399
• 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: Nagoya University
• Principal Investigator: NAKAZAWA Yuka 名古屋大学, 環境医学研究所, 講師 (00533902)
• Co-Investigator(Kenkyū-buntansha): 荻 朋男 名古屋大学, 環境医学研究所, 教授 (80508317)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 転写と共役したDNA修復 / RNAポリメラーゼ / ユビキチン化

Outline of Final Research Achievements

Genomic DNA, which contains our genetic information, is constantly exposed to damage from both internal and external sources. Transcription-coupled repair (TCR) is a system that efficiently repairs DNA damage in actively transcribed regions, playing a crucial role in maintaining homeostasis and preventing genomic instability. In this study, we investigated the molecular mechanisms of TCR and the pathogenesis of human diseases associated with deficiencies in this system. Our research has provided several novel insights into the critical role of TCR in genome maintenance.

Free Research Field

DNA修復学、分子細胞生物学、人類遺伝学

Academic Significance and Societal Importance of the Research Achievements

TCRの破綻は、早期老化や進行性の神経変性、好発がん、発育・発達異常などを示す様々な遺伝性疾患の原因となることが知られており、TCRの分子メカニズム解明と各種病態との関係を明らかにすることは、遺伝性疾患のみならず、一般的な老化やがんなどの治療薬/緩和薬/予防薬の開発に役立つだけでなく、新たな診断法の構築やバイオマーカーの探索など、広範囲の医療分野に貢献してゆくと期待される。