| Budget Amount *help |
¥132,600,000 (Direct Cost: ¥102,000,000、Indirect Cost: ¥30,600,000)
Fiscal Year 2014: ¥24,180,000 (Direct Cost: ¥18,600,000、Indirect Cost: ¥5,580,000)
Fiscal Year 2013: ¥25,480,000 (Direct Cost: ¥19,600,000、Indirect Cost: ¥5,880,000)
Fiscal Year 2012: ¥26,650,000 (Direct Cost: ¥20,500,000、Indirect Cost: ¥6,150,000)
Fiscal Year 2011: ¥26,390,000 (Direct Cost: ¥20,300,000、Indirect Cost: ¥6,090,000)
Fiscal Year 2010: ¥29,900,000 (Direct Cost: ¥23,000,000、Indirect Cost: ¥6,900,000)
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| Outline of Final Research Achievements |
We have identified chromatin remodeling factors of BAF complex required for accumulation of KU proteins at DNA double-strand breaks (DSB) and its repair by NHEJ. Among the factors are ARID1A recently determined as one of the most frequent mutation in various cancer cells and other factors, which are silenced very often in cancer cells. These cells are also sensitive to a common cancer therapy drug cisplatin. Therefore, many of cancer cells are at least partly DNA repair deficient, suggesting that effective cancer therapy can be predicted by the analysis of the chromatin remodeling factors. Another finding of this project was the mechanisms of transcriptional repression at DSB. In response to DSB ATM is activated and ENL, a factor in the transcriptional elongation complex, is phosphorylated by the ATM, that enables to recruit the Polycomb complex PRC1 to the site, which ubiquitinates histone H2A leading to the repression of transcription at the site and DSB repair proteins at the site.
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