| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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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| Research Abstract |
Ku and XLF are essential factors for non-homologous end-joining (NHEJ) that is a major mechanism for DNA double-strand break repair. An R57G substitution in XLF protein has been identified in patients with hereditary hypersensitivity to ionizing radiation. In this study, we performed detailed analysis of the interaction between Ku and XLF and evaluated the effects of inositol-6-phosphate, which is known to augment NHEJ in cell-free systems, on the Ku-XLF interaction. Live cell imaging demonstrated that XLF protein with the R57G substitution (XLF R57G) localizes in nucleus and accumulates at sites of DNA damage, similar to wild-type XLF. Ubiquitination was detected in XLF R57G, but not in wild-type XLF, suggesting the causal relationship with hyper-radiosensitivity in patients harboring this mutation.
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