GENE CONTROL IN INFECTION AND LYSOGENY BY PHAGE LAMBDA

正常和病理条件下的基因表达由 RNA 聚合酶介导 酶是一类复杂的多亚基分子机器，具有高度的 进化中保守的。 RNA聚合酶的功能不仅在水平上受到控制 获取基因（转录起始），而且还可以在 RNAP 的酶进展过程中进行 执行基因信息的顺序读出。此类的一个重要例子是 控制发生在 HIV 病毒中，并由其主要调节因子 TAT 基因介导。的 用于理解转录中涉及的酶机制的中心模型 调节是大肠杆菌噬菌体 lambda 的抗终止蛋白， 其基因Q和N的产物。该项目研究该基因的作用机制 Q 蛋白，它修饰 RNA 聚合酶的起始位点附近，但随后变成 酶的亚基，使其能够更有效地延长并通过 转录终止信号。我们将发现 Q 的重要元素 多肽和 RNA 聚合酶亚基，其物理和功能所需 功能相互作用，特别是介导初始作用的西格玛起始因子 Q 蛋白与 RNA 聚合酶的结合，我们将研究改变的酶促 Q-修饰的RNA聚合酶的特性。我们将研究其机制 转录终止和调节蛋白干扰的方式 这个过程。

Gene expression in normal and pathological conditions is mediated by RNA polymerase enzymes, a family of complex, multisubunit molecular machines that is highly conserved in evolution. RNA polymerase function is controlled not only at the level of access to genes (transcription initiation), but also during enzyme progression as RNAP carries out its sequential readout of the gene message. An important example of such control occurs in HIV virus and is mediated by its major regulator, the TAT gene. The central models for understanding enzymatic mechanisms involved in transcriptional regulation are the antitermination proteins of the E. coli bacteriophage lambda, the products of its genes Q and N. This project studies the mechanism of action of the gene Q protein, which modifies RNA polymerase near its initiation site, but then becomes a subunit of the enzyme, allowing it to elongate more efficiently and to progress through transcription termination signals. We will discover important elements of both the Q polypeptide and the subunits of RNA polymerase that are required for their physical and functional interaction, particularly the sigma initiation factor which mediates the initial engagement of Q protein with RNA polymerase, and we will study the altered enzymatic properties of Q-modified RNA polymerase. We will investigate the mechanism of transcription termination and the manner in which regulatory proteins interfere with this process.