Elucidation of homologous recombination repair by mRNA processing and application to ovarian cancer treatment

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16759
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: The University of Tokyo
• Principal Investigator: TANIKAWA MICHIHIRO 東京大学, 医学部附属病院, 助教 (70706944)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 卵巣癌 / DNA損傷修復 / 相同組換え修復 / mRNAプロセッシング

Outline of Final Research Achievements

In this research project, we revealed the role of the mediator complex as a novel DNA damage repair factor in maintaining genomic stability. Specifically, in comprehensive genome wide screens, we extracted mediator complex factors as novel DNA damage candidate factors and identified which steps in the DNA damage repair pathway are regulated. In addition, we established an experimental system for observing the dynamics of a novel factor at the DNA damage site using live cell imaging technique by a confocal microscope, and identified the upstream regulatory pathway by inhibitors and siRNA. The mRNA processing pathway involving the mediator complex is frequently mutated in multiple cancer types, suggesting that it may become a novel therapeutic marker or target in the future.

Free Research Field

婦人科悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

新規のDNA損傷修復因子としてmRNAプロセッシングに関わるメディエーター複合体を同定した。DNA損傷修復、特に相同組換え修復能の異常は卵巣癌の治療標的として確立されており、メディエーター複合体の機能失活が相同組換え修復異常につながる可能性を初めて示すことになる。メディエーター複合体を含むmRNAプロセッシング経路は複数の癌種で高頻度に変異を呈しており、将来的には新規の治療マーカーや治療標的につなげられる可能性がある。