GENE CONTROL IN INFECTION AND LYSOGENY BY PHAGE LAMBDA

正常和病理条件下的基因表达是由RNA聚合酶介导的 酶，一系列复杂的，多亚单位分子机器，高度 在进化中保守。RNA聚合酶的功能不仅在水平上被控制 获得基因(转录启动)，但也在酶的进程中作为RNAP 对基因信息进行顺序读出。这是一个重要的例子 控制发生在HIV病毒中，并由其主要调节因子Tat基因介导。这个 理解转录相关酶机制的中心模型 调节的是大肠杆菌噬菌体lambda的抗终止蛋白， 其基因Q和N的产物。本项目研究该基因的作用机制 Q蛋白，它在其起始点附近修饰RNA聚合酶，但随后成为一种 酶的亚基，使其能够更有效地伸长并通过 转录终止信号。我们将发现这两个问题的重要元素 多肽和RNA聚合酶的亚单位，是它们的物理和 功能相互作用，特别是调节初始的西格玛启动因子 Q蛋白与RNA聚合酶的结合，我们将研究改变的酶 Q修饰的RNA聚合酶的性质。我们将研究其发生机制。 转录终止和调控蛋白干扰的方式 这一过程。

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.