| Project/Area Number |
23659587
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Radiation science
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| Research Institution | Tottori University |
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Principal Investigator |
KURIMASA Akihiro 鳥取大学, 大学院・医学系研究科, 准教授 (80343276)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 放射線腫瘍学 / バイオセンサー / DNA修復 / 細胞周期 / 抗がん剤 / 放射線 |
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| Research Abstract |
Tumor suppressor p53 Binding Protein 1(53BP1) is recruited rapidly to sites of DNA double-strand breaks (DSBs) and participates in the cellular response to DNA damage. We exploited property of 53BP1 that accumulate in DSB sites and developed biosensor detecting DNA damage using the specical form of 53BP1-GFP fusion protein that could express stably in the cell. Futhermore, we built a system that can identify the difference of cell cycle stage by intranuclear localization patterns of PCNA-DsRed. U2OS cell lines (U2RDP-LE53-21) expressing both these fluorescent fusion proteins make it possible to observe DSBs occurred in different cell cycle stage, these cells remain living. Here, we show how 53BP1 foci are observed in normal culturing conditions, and also how DSBs 53BP1 foci are induced by chemical agents such as Neocarcinostatine (NCS) or DNA Topoisomerase I inhibitor Camptothesin (CPT) that are well-known DSBs inducers. The number of 53BP1 foci was increased by these chemical agents and cell cycle distribution was prolonged compare to cells in normal culture condition. U2OS cell lines may be available for the screening chemotherapy drugs and radiosensitizers that induce DSBs in cancer cells.
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