Investigation for the regulatory mechanism of DNA double-strand break repair by nuclear myosin

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K12244
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 63020:Radiation influence-related
• Research Institution: Tokyo University of Technology
• Principal Investigator: Nishi Ryotaro 東京工科大学, 応用生物学部, 准教授 (80446525)
• Co-Investigator(Kenkyū-buntansha): 逆井 良 金沢医科大学, 医学部, 准教授 (10549950)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: DNA修復 / 相同組換え修復 / 核内ミオシン / DNA二本鎖切断

Outline of Final Research Achievements

DNA double-strand break (DSB) that is caused by ionizing radiation etc. is one of the most deleterious types of DNA damage. In human cells, DSBs are mainly repaired by either homologous recombination or non-homologous end joining. Since MRN (MRE11-NBS1-RAD50) complex regulates pathway choice, initiation of homologous recombination, and DSB responses, revealing regulatory mechanism of MRN complex is mandatory to understand DSB repair. This research aimed to unveil regulatory mechanism of MRN complex by characterizing newly identified MRN complex interactor, nuclear myosin. We found that nuclear myosin interacted with MRN complex in nuclei and mainly interacted with MRE11. In addition, we also found that nuclear myosin facilitated homologous recombination.

Free Research Field

DNA修復

Academic Significance and Societal Importance of the Research Achievements

これまでにDSB修復の基本的な分子機構が解明されてきた。近年ではDSB修復はDSBが生じたゲノム上の転写活性や、隣接する核内構造体等によって複雑な制御を受けることが明らかにされつつあり、ヒト細胞核内ではDSB修復は画一的な反応ではなく、複数のサブパスウェイから構成されることが示唆されている。本研究では、正確性の高いDSB修復機構である相同組換え修復に促進的に機能する因子を新たに同定し、その細胞生存における重要性を明らかにした。このことは、ゲノム安定性維持という生命の根幹をなす現象に新たな視点を加えるだけでなく、遺伝子領域におけるゲノム編集の正確な効率化に利用することも可能であると考えられる。