The goal of this research project is to understand the structure and function of the histone binding protein NASP (nuclear autoantigenic sperm protein). Previously NASP was thought to e a testis and sperm specific protein; however, over the past four years we have discovered that the NASP gene is alternatively spliced to express a somatic form (sNASP) that is present in all mitotic cells. Consequently, our current hypothesis is that NASP is important for normal cell function during both mitosis and meiosis. By transporting histone H1 variants into the nucleus, NASP is likely to participate in the regulation and/or reorganization of chromatin structure during both DNAS synthesis and in subsequent meiotic phosphases.
The Specific Aims of this proposal are: 1) to determine the relationship between NASP and the cell cycle in both mitotic and meiotic cells.
This aim will test the hypothesis that NASP is required for progression through S-phase and that during spermatogenesis it is further required for histone/transition protein/protamine exchange, 2) to determine which specific histones are bound to NASP in primary spermatocytes, round spermatids and unfertilized oocytes to test the hypothesis that NASP is promiscuous and binds any histone, transition protein or protamine in the testing, and any histone in the oocyte, 3) to determine how the testicular and somatic forms of the NASP gene are regulated, and 4) to determine whether the stem loop binding protein(SLBP) and tNSAP mRNAs, similar to the testis-specific histones, are synthesized independently of DNA replication during spermatogenesis of whether they simply persist after the end of the last S-phase. We will also determine when SLBP protein first appears during spermatogenesis, whether SLBP mRNA is translationally regulate din post-meiotic spermatids, and whether SLBP is associated with specific testicular histone mRNAs as part of the translational regulation of the mRNAs.
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