Elucidation of molecular level of the linkage between DNA damage response and chromatin conformational changes

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20631
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0701:Biology at molecular to cellular levels, and related fields
• Research Institution: Osaka University
• Principal Investigator: Isobe Shin-Ya 大阪大学, 大学院理学研究科, 助教 (50897147)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: ヘテロクロマチン / DNA損傷修復 / R-loop

Outline of Final Research Achievements

High condensed structure chromatin, it’s called heterochromatin, results in a resolution of chromatin structure upon DNA damage, making it accessible to repair factors. R-loop (DNA-RNA hybrid) has recently be focused on one of structure that plays a platform of condensation in heterochromatin, and excessive accumulation of R-loop is known to induce DNA damage. Through this study, we found AHDC1, which has heterochromatin conformational conversion activity, binds to DNA repair proteins and is involved in the resolution of R-loop, and concluded that it is an important factor in linking heterochromatin and DNA repair.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

DNA修復に関わる遺伝子の変異は様々な疾患の原因となることが知られている。また、R-loop解消に関わる遺伝子の変異は、DNA複製、転写、DNA修復といったDNAの上で起こる様々な生命現象に異常が生じ、その結果として、がんや神経系の発達異常など様々な疾病の原因となると考えられている。AHDC1はDNA修復に関わるタンパク質と結合することや、R-loop解消に関わること、加えて、AHDC1変異が精神遅滞を引き起こす報告もあることから、AHDC1の機能解析が、それらの疾患の解決への糸口になり得る。