| Budget Amount *help |
¥3,950,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
The actin family consists of conventional actins and various actin-related proteins (Arps). The members of the actin family was evolved from the common ancestral molecule and share the basal structure. The function of actin has been studied extensively for a long time. On the other hand, since the identification of Arps was first reported rather recently (in 1992), Arps have not yet been fully characterized or analyzed. In Saccharomyces cerevisiae, some of chromatin remodeling and histone acetyltransferase complexes, and these nuclear Arps have multiple functions including the regulation of chromatin remodeling and histone acetyltransferase complexes. Nuclear Arps of vertebrates are also supposed to possess similar function; however, identification and analyses of nuclear Arps in vertebrates are just beginning. We indicated that a nuclear Arp of human, hArp5, was localized in the nucleus as well as yeast Arp5p and these two had evolutionarily conserved functions. We also found that hArp5 shuttled between the nucleus and the cytoplasm as well as actin. Importantly, hArp5 depletion by siRNA caused defect in the accumulation of phosphorylated H2AX (gamma-H2AX) in the process of DNA double-strand break (DSB) repair. Taken together with the observations that hArp5 stably associates with the hIno80 chromatin remodeling enzyme and is required for chromatin binding of hIno80, it is suggested that hArp5 has a regulatory role in DSB repair through the chromatin remodeling machinery of the INO80 complex. Recent yeast studies show that the yeast INO80 complex is required also for DNA replication processes. We also showed that anther human nuclear Arp, hArp8, was involved in chromosome segregation.
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