MECHANISMS OF ESCHERICHIA COLI CHROMOSOMAL REPLICATION

在大肠杆菌中的染色体复制是 严格配合细菌的生长速度。这 协调通过事件来控制，这些事件调节 每个复制周期的启动频率。《长河》 这项拟议研究的范围目标是了解 从生物化学角度看，染色体复制是如何发生的， 以及它是如何被调节的，以及如何与其他细胞过程相耦合。 拟议研究的一种方法涉及生化 DNAA蛋白突变形式的鉴定 使这些基因发生突变的生化变化 不能在复制启动中起作用的蛋白质。这个 第二个相互关联的方法涉及生化 外源基因编码的基因产物的特性 Dna A突变体的抑制子以了解 抑制机制。这些研究将使我们深入了解 DNA复制的启动机制，DNAA的作用 启动中的蛋白质以及其他与DNAA相互作用的因素 蛋白质，并有助于启动复制。 对引发过程及其影响因素的生物化学认识 监管将提供一个框架，说明这些过程如何 发生在高等生物体中，哪些事件可能会诱发恶性 正常静止的细胞的生长，以及这些异常 过程可以被控制或阻止。

Chromosomal replication in the bacterium Escherichia coli is strictly coordinated to the growth rate of the bacterium. This coordination is controlled through events which regulate the frequency of initiation of each cycle of replication. The long range objective of this proposed research is to understand biochemically how initiation of chromosomal replication occurs, and how it is regulated and coupled to other cellular processes. One approach of the proposed research involves biochemical characterization of mutant forms of dnaA protein to identify the biochemical alterations which make these mutationally altered proteins unable to function in initiation of replication. The second interelated approach involves biochemical characterization of gene products encoded by extragenic suppressors of dnaA mutants in order to understand the mechanism of suppression. These studies will lend insight into the mechanism of initiation of DNA replication, the function of dnaA protein in initiation, and other factors which interact with dnaA protein and contribute to the initiation of replication. A biochemical understanding of the initiation process and its regulation will provide a framework for how these processes may occur in higher organisms, what events may induce the malignant growth of normally quiescent cells, and how these abnormal processes may be controlled or prevented.