GENETIC AND CHEMICAL STUDIES OF PHAGE LAMBDA DEVELOPMENT

长期目标是生命周期的分子图景 噬菌体2和利用这些信息来帮助理解 原核生物和真核生物DNA交易的一般特征。这个 本赠款期间的主要具体目标侧重于理解两个 病毒生长的几个方面：(1)裂解和溶源之间的转换 噬菌体发育途径；(2)DNA的启动和调控 复制。此外，在 Lambda工作将被用来学习一些关于复杂的东西 大肠杆菌中的转录调控、热休克和蛋白质周转 以及关于在大肠杆菌中复制叉处的相互作用 真核病毒SV40。关于在时间和时间之间切换的知识 通路很可能有助于理解正常和异常 人类的发展。对DNA复制的调控与 了解恶性细胞的不受控制的生长。 关于裂解和溶源之间的转换的工作将集中在 调控Lambda周转的生化机制 CII蛋白，这似乎是控制的主要特征 路径的选择。蛋白质分解反应及其调控将是 用纯化的蛋白质进行研究。对于DNA复制，实验 将重点放在核蛋白的组装和拆解反应上 控制双向复制路线的波长起始点 在复制分叉处的链生长复合体上。这个 拆解反应由热休克蛋白DNAJ和 DNAK等复制分叉。进行拆卸反应 通过热休克蛋白DNAJ和DNAK等进行复制 系统提供了一种了解热休克的细胞作用的方法 回应。其他实验将试图详细了解两个 可能涉及DNA损伤的转录调控系统 核蛋白复合体：半乳糖和氨同化(GlnA)。

The long-term objectives are a molecular picture of the life-cycle of bacteriophage 2 and the use of this information to help understand general features of DNA transactions in prokaryotes and eukaryotes. The major specific aims for this grant period focus on understanding two aspects of viral growth: (1) The switch between the lytic and lysogenic pathways of phage development; (2) initiation and regulation of DNA replication. In addition, the insights and techniques developed in the lambda work will be used to learn something about complex transcriptional regulation, heat shock, and protein turnover in E. coli and about interactions at replication forks in E. coli and the eukaryotic virus SV40. Knowledge about a switch between temporal pathways is likely to be useful in understanding normal and abnormal development in humans. Regulation of DNA replication has relevance to understanding the uncontrolled growth of malignant cells. The work on the switch between lysis and lysogeny will concentrate on biochemical mechanisms responsible for the regulated turnover of lambda cII protein, which appears to be the major feature controlling the choice of pathways. The proteolytic reaction and its regulation will be investigated with purified proteins. For DNA replication, experiments will focus on the nucleoprotein assembly and disassembly reactions at the lambda origin that control the route to bidirectional replication and on the chain growth complex at the replication fork. The disassembly reaction is carried out by the heat shock proteins DnaJ and DnaK, and so the replication fork. The disassembly reaction is carried out by the heat shock proteins DnaJ and DnaK, and so the replication system provides a way to learn about the cellular role of the heat shock response. Other experiments will seek to understand in detail two transcriptional regulatory systems that may involve DNA-wound nucleoprotein complexes: galactose and ammonia assimilation (glnA).