Elucidation of the role of chromatin structure on genome instability using genome editing technique

2015 Fiscal Year Final Research Report

• Project/Area Number: 25281019
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Osaka University
• Principal Investigator: Fujiwara Tomoko (石川智子) 大阪大学, 医学(系)研究科(研究院), 助教 (70402922)
• Co-Investigator(Renkei-kenkyūsha): Todo Takeshi 大阪大学, 大学院医学系研究科, 教授 (90163948)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: メダカ / 損傷メモリー / 遺伝的不安定性 / マイクロサテライト不安定性 / 環境ストレス / エピジェネティック変化 / クロマチン構造変化 / ゲノム編集技術

Outline of Final Research Achievements

Genetic instability induced by radiation or chemical mutagens is an interesting phenomenon and plays an important role on carcinogenesis, which appear through long latency period. The factor based under these phenomena is considered to "damage memory", however its entity is not clear. Based on several reports, we hypothesized an epigenetic events such as DNA and histone modification significantly contribute to the "damage memory". In this study, to test the hypothesis we have established a system for detecting the genetic instability. For inducing double strand breaks (DSBs) we used CRISPR, by which we can introduce DSBs at any genomic sequence we want and for the target of genetic instability that on microsatellite was tested. In addition, we have constructed BAC vector containing the entire genome region of ATR or DNA-PKcs gene for the rescue of each mutant, respectively.

Free Research Field

分子放射線生物学