Molecular mechanism of genomic instability by RNA editing

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07251
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Kyoto University
• Principal Investigator: Kobayashi Maki 京都大学, 医学研究科, 特定准教授 (20400690)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 抗体遺伝子 / AID / クラススイッチ / 体細胞突然変異 / トポイソメラーゼ１

Outline of Final Research Achievements

One of the basic principles of "immunity" is the diversification of antibody genes, which is one of the mechanism of infection defense symbolized by the fact that you never suffer from measles twice. We elucidated a part of the complex story, how antibody genes are efficiently recombined in vivo to create a defense system. The topoisomerase 1 (Top1) presents in all the cells and have both function of maintenance of the integrity of the genomic DNA and also of destabilization the genomic DNA. By our study it was discovered that AID expressed only in immune B cells regulates Top1 by suppressing its translation and achieves highly efficient and specific gene recombination of antibody genes to produce diversified antibody proteins.

Free Research Field

細胞分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究を活かして抗体遺伝子組換えの効率化促進が可能になれば、感染防御システムを強化し、病原微生物の変化に迅速に対応する治療法が開発される可能性がある。トポイソメラーゼ１はすべての細胞に発現しているため、AID以外の細胞への刺激などがトポイソメラーゼ１の制御を介して細胞のがん化をもたらす分子機構が発見される可能性がある。また、トポイソメラーゼ１が不安定化することを防ぐ薬剤を発見できれば、一生の間にゲノムDNAに蓄積しがん化につながる遺伝子変異を最小限に抑えることができるかもしれない。