Mechanisms of Yeast Transcriptional Regulators

超出所提供的空间。这项建议有两个长期目标。第一个是理解，在精确的分子条件下，高度保守的基因转录阻遏物的作用机制。这项工作将与S。酿酒酵母Ssn6-Tupl阻遏蛋白，并强调使用纯化的蛋白质的生化和结构的方法，旨在推断分子机制。遗传方法在S.包括广泛使用微阵列技术在内的酿酒酵母基因芯片将被用于测试来自生化实验的模型，并作为探索性工具。第二个长期目标是描述S.酿酒酵母和几种相关的酵母，包括利用Ssn6-Tupl的所有DNA结合蛋白和由每个DNA结合蛋白控制的完整基因组。这项工作的最终目标是了解由高度保守的组件组成的调节电路如何在进化的时间尺度上变得专业化。考虑到真核生物中基因调控蛋白和一般转录因子的高度保守性，本提案中为酵母蛋白开发的许多原则似乎也适用于其他环境。对细胞特化背后的分子事件的基本理解不仅为理解该过程如何失败提供了框架，而且还为设计基于干预的治疗策略提供了基础和知识。性能现场=

EXCEED THE SPACE PROVIDED. This proposal has two long-term goals. The first is an understanding, in precise molecular terms, of the mechanism of action of highly conserved represser of gene transcription. This work will be carried out with the S. cerevisiae Ssn6-Tupl represser and emphasizes the use of purified proteins for biochemical and structural approaches designed to deduce molecular mechanisms. Genetic approaches in S. cerevisiae, which include the extensive use of microarray technologies will be used to test models derived from biochemical experiments and as exploratory tools. The second long-term goal is a description of the entire Ssn6-Tupl regulatory network in S. cerevisiae and several related yeasts, including all the DNA-binding proteins that utilize Ssn6-Tupl and the complete sets of genes controlled by each DNA-binding protein. The ultimate goal of this work is an understanding of how regulatory circuits that are composed of highly conserved components become specialized over evolutionary time scales. Given the high degree of conservation of gene regulatory proteins and general transcription factors among eucaryotes, it seems likely that many of the principles developed for the yeast proteins covered in this proposal will apply in other settings. A basic understanding of the molecular events underlying cell specialization provides not only a framework for understanding how the process can fail, but also provides the substrates and knowledge to design therapeutic strategies based on intervention. PERFORMANCE SITE ========================================Section End===========================================