Elucidation of genome stabilization mechanism involving RNA editing enzyme ADAR1

Research Project

Project/Area Number	16K20895
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Risk sciences of radiation and chemicals Tumor biology
Research Institution	Hirosaki University
Principal Investigator	Ariyoshi Kentaro 弘前大学, 被ばく医療総合研究所, 助教 (50462750)
Research Collaborator	Nishikura Kazuko
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000) Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords	RNA編集 / ゲノム不安定化 / DNA損傷 / ゲノム安定化 / ADAR1 / DNA二重鎖切断 / ゲノム不安定性 / DNA損傷修復 / 遺伝子 / ゲノム
Outline of Final Research Achievements	The purpose of this study is to investigate the cross-talk function of RNA editing and DNA repair mechanism by examining how ADAR1 protein with RNA editing function is involved in genome stabilization. As a result, we found that ADAR1 protein accumulates at the DNA double-strand break site, and furthermore, we observed higher radiosensitivity of cells after knock down of ADAR1 expression. ADAR1 suppression also showed a delay of DNA damage repair. These results suggest that ADAR1 protein plays an important role in DNA damage repair.
Academic Significance and Societal Importance of the Research Achievements	DNA修復機構の破綻は細胞のがん化と密接な関連を持つことから、細胞がん化にADAR1の機能不全が影響している事が考えられ、得られた結果から、細胞のがん化とRNA 編集機構の接点、およびRNA編集機構によるがん抑制機構の発見への可能性が考えられる。