Development of new radiosensitizer based on the molecular mechanism of the recognition and repair of DNA double-strand break
| Project/Area Number |
24390290
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2014: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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| Keywords | 放射線 / 癌治療 / DNA二重鎖切断 / DNA修復 / DNA依存性プロテインキナーゼ / XRCC4 / DNA ligase IV / タンパク質リン酸化 / 癌 / 増感剤 / 放射線治療 / 放射線増感剤 / DNA二重鎖切断修復 / DNA損傷応答 / 蛋白質リン酸化 / DNA-PK |
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| Outline of Final Research Achievements |
This study aimed to clarify the regulatory mechanisms of protein-protein interaction mediated through DNA damage-induced phosphorylation of XRCC4 by DNA-PK and to explore their potential in application to the development of new radiosensitizer. The main achievements of this study include finding the importance of XRCC4 extremely C-terminal (XECT) region, which is highly conserved among vertebrates, the mechanisms of the nuclear localization and chromatin binding of XRCC4/LIG4 complex and the detection of XRCC4 S320 phosphorylation by DNA-PK in living cells. Based on these results, we tested possible radiosensitizing effects of XRCC4 phosphorylation-mimicking synthetic peptide, but the expected effects were not obtained, requiring further studies to optimize peptide sequence and the protocol of introduction into cells.
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Report
(5 results)
Research Products
(62 results)
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[Journal Article] LIG4 mediates Wnt signaling-induced radioresistance2016
Author(s)
Jun S, Jung Y-S, Suh HN, Wang W, Kim MJ, Oh YS, Lien E, Shen X, Matsumoto Y, McCrea P, Li L, Chen J, *Park J-I.
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Journal Title
Nature Communications
Volume: 7
Pages: 10994-10994
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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