Elucidation of transcription-coupled chromosomal translocation pathways between gene loci

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K21536
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: Gunma University
• Principal Investigator: Shibata Atsushi 群馬大学, 未来先端研究機構, 准教授 (30707633)
• Co-Investigator(Kenkyū-buntansha): 山内 基弘 九州大学, アイソトープ統合安全管理センター(馬出地区), 准教授 (60437910) ; 安原 崇哲 東京大学, 大学院医学系研究科(医学部), 助教 (90757056)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: DNA二本鎖切断 / 放射線 / 染色体転座

Outline of Final Research Achievements

Chromosomal translocations that are critical to tumorigenesis are caused by misrepair of DNA double-strand break (DSB). However, the processes by which chromosomal translocations between gene loci that lead to tumorigenesis is largely unknown. In the research project, we aimed to examine DSB-induced chromosomal translocation between transcriptionally active loci by establishing a human cultured cell experimental system that artificially induces DSBs at arbitrary locations and timings. We constructed a system in which the restriction enzyme AsiSI is induced into the nucleus by tamoxifen analog, 40HT, in retinal pigment epithelial cells, and created an assay for detecting DSB chromosomal translocation.

Free Research Field

DNA損傷応答

Academic Significance and Societal Importance of the Research Achievements

DNA二本鎖切断（DSB: DNA double strand break）は、その修復エラーにより重篤なゲノム不安定化を引き起こす。実際、DSB修復異常によって引き起こされるゲノム不安化はがん発症に強く繋がることから、DSB修復研究は人の健康維持に必要不可欠な研究課題である。本研究課題では、発がんに繋がるゲノム不安定化の中でも特に重篤な染色体転座の発生機構の研究を行った。その原理解明は、人体における発がん抑制のための治療戦略の開発に繋がる。