Yeast Histone Acetylases and Sir2-like Deacetylases

描述（来自申请人摘要的逐字逐句）： 本研究旨在了解组蛋白乙酰化的作用， 染色质结构和功能的脱乙酰化，使用酵母 酿酒酵母来研究这些过程。因为许多酵母 参与乙酰化/脱乙酰化的蛋白质具有人类同源物， 该项目应该揭示人类生物学和疾病。具体目标为 这一时期是：1）了解Sir 2的酶机制和相关的 蛋白质，最近被证明是NAD依赖性蛋白质脱乙酰酶，2） 确定Sir 2在转录沉默中的作用是否是组蛋白 脱乙酰化，3）确定酵母Sir 2同源物的体内作用 Hst 2、Hst 3和Hst 4，4）了解蛋白质SUM 1 -1和Hst 1如何 在Sir 2不存在的情况下沉默交配型基因座HML和HMR，和5） 证明酵母蛋白Sas 2和SptlO是乙酰转移酶， 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,