| Budget Amount *help |
¥446,160,000 (Direct Cost: ¥343,200,000、Indirect Cost: ¥102,960,000)
Fiscal Year 2014: ¥84,630,000 (Direct Cost: ¥65,100,000、Indirect Cost: ¥19,530,000)
Fiscal Year 2013: ¥84,630,000 (Direct Cost: ¥65,100,000、Indirect Cost: ¥19,530,000)
Fiscal Year 2012: ¥84,630,000 (Direct Cost: ¥65,100,000、Indirect Cost: ¥19,530,000)
Fiscal Year 2011: ¥95,810,000 (Direct Cost: ¥73,700,000、Indirect Cost: ¥22,110,000)
Fiscal Year 2010: ¥96,460,000 (Direct Cost: ¥74,200,000、Indirect Cost: ¥22,260,000)
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| Outline of Final Research Achievements |
Activation-induced cytidine deaminase (AID)-dependent immunological memory is engraved in immunoglobulin (IgH) gene and initiated by DNA breaks. Precise molecular mechanism of Topoisomerase1 (Top1)'s involvement in AID-induced DNA breaks was analyzed. This result corrected the previous DNA deamination theory. In type 5 hyper IgM syndrome caused by UNG deficiency, class switch recombination (CSR) is abolished, however, somatic hyper-mutation (SHM) is maintained. Molecular mechanism of UNG in CSR and SHM is analyzed and the results is sufficient for explaining this difference between these two syndrome. AIS has two independent functions of DNA breaks and DNA repair which are dependent on N-terminus and C-terminus domain of AID, respectively. The function-specific cofactors, hnRNP K for DNA breaks and hnRNP L for DNA repair are identified and analyzed. DNA breaks and repair steps are conducted in the chromatin structure. We showed that AID-induced IgH gene recombination requires the specific chromatin structure. Actually molecular function of chromatin remodeller SMARCA4, transcription elongation factor Spt4/5 complex and Brd4 which binds to acetylated lysine in IgH diversification were analyzed.
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