Yeast Histone Acetylases and Sir2-like Deacetylases

描述(逐字摘自申请者摘要)：长期目标 本研究旨在了解组蛋白乙酰化和蛋白水解酶的作用。 利用酵母对染色质结构和功能进行脱乙酰化 酿酒酵母来研究这些过程。因为许多酵母菌 参与乙酰化/去乙酰化的蛋白质有人类同源物，这 该项目应该阐明人类生物学和疾病。具体目标是 这一阶段是：1)了解Sir2的酶机制和相关的 蛋白质，最近被证明是依赖于NAD的蛋白质脱乙酰酶，2)到 确定Sir2在转录沉默中的作用是否是组蛋白 去乙酰化，3)确定酵母Sir2同系物在体内的作用 Hst2，Hst3和Hst4，4)，以了解蛋白Sum1-1和Hst1如何 在没有Sir2的情况下，使交配型基因座HML和HMR沉默，以及5) 证明酵母蛋白SAS2和SptlO是乙酰转移酶和 为了确定它们的底物是组蛋白还是其他蛋白质，

DESCRIPTION (Verbatim from the applicant's abstract): The long term goal of this research is to understand the role of histone acetylation and deacetylation in chromatin structure and function, using the yeast Saccharomyces cerevisiae to study these processes. Since many of the yeast proteins involved in acetylation/deacetylation have human homologs, this project should shed light on human biology and disease. The specific aims for this period are: 1) to learn about the enzymatic mechanism of Sir2 and related proteins, recently demonstrated to be NAD-dependent protein deacetylases, 2) to determine if the role of Sir2 in transcriptional silencing is histone deacetylation, 3) to determine the in vivo roles of the yeast Sir2 homologs Hst2, Hst3 and Hst4, 4) to understand how the proteins SUM1-1 and Hstl can silence the mating type loci, HML and HMR, in the absence of Sir2, and 5) to demonstrate that the yeast proteins Sas2 and SptlO are acetyltransferases and to determine if their substrates are histones or other proteins,