TESTIS SPECIFIC HISTONE BINDING PROTEIN (NASP)

点击翻译按钮获取中文摘要

Description (provided by applicant): 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 be a testis and sperm specific protein; however, over the past four years the applicant has discovered that the NASP gene is alternatively spliced to express a somatic form (sNASP) that is present in all mitotic cells. Consequently, his current hypothesis is that NASP is important for normal cell function during both mitosis and meiosis. By transporting histone HI variants into the nucleus, NASP is likely to participate in the regulation and/or reorganization of chromatin structure during both DNA synthesis and in subsequent meiotic prophases. 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 testis, 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 testicular (t)NASP mRNAs, similar to the testis-specific histones, are synthesized independently of DNA replication during spermatogenesis or whether they simply persist after the end of the last S-phase.