Functional analysis of ubiquitin ligase RNF126

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K10432
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Tohoku University
• Principal Investigator: Ishida Noriko 東北大学, 東北メディカル・メガバンク機構, 助教 (10361073)
• Co-Investigator(Kenkyū-buntansha): 中川 直 山陽小野田市立山口東京理科大学, 薬学部, 講師 (30707013)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: DNA損傷修復 / ユビキチン / E3リガーゼ / タンパク分解 / ノックアウトマウス

Outline of Final Research Achievements

It was reported that E3 ligase RNF126 ubiquitinates Ku80, which plays an important role in DSB repair, and promotes the completion of repair (Ishida N et al. Mol Cell Biol. 2017; 37: e00347-16).
As a result of producing and analyzing RNF126 knockout (KO) mice, a decrease in T cells and sperm was observed. It was also confirmed that the phenotype obtained using the human cell line can be reproduced in KO mouse primary cells. Furthermore, as a result of producing and analyzing RNF126 CKO mice, it was clarified that RNF126 plays an important role in germ cell development in the testis.

Free Research Field

生化学、細胞生物学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

ヒト細胞における、DNA損傷修復に重要なKu複合体を分解制御する新たな因子RNF126を発見・論文報告したことにより、DNA修復の二重鎖切断修復メカニズムの理解に貢献できた。また、RNF126のマウス個体レベルでの機能、T細胞や精子細胞分化における重要性を明らかにしたことより、T細胞維持や精子形成におけるユビキチンリガーゼやタンパク分解の理解に貢献できる可能性に繋がった。