| 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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| 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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