MECHANISMS OF ESCHERICHIA COLI CHROMOSOMAL REPLICATION

大肠杆菌中的染色体复制是 与细菌的生长速度严格协调。 这 协调是通过事件来控制的， 每个复制周期开始的频率。 长 这项研究的目的是了解 从生物化学上讲，染色体复制是如何开始的， 以及它是如何被调节并与其他细胞过程相结合的。 一种研究方法涉及生物化学 表征dnaA蛋白的突变形式以鉴定 生物化学的改变， 不能在复制起始中起作用的蛋白质。 的 第二个相互关联的方法涉及生物化学 基因外编码的基因产物的表征 dnaA突变体的抑制子，以了解 抑制机制。 这些研究将有助于深入了解 DNA复制起始机制，dnaA的功能 起始蛋白以及其他与dnaA相互作用的因子 蛋白质，并有助于复制的启动。 从生物化学的角度理解启动过程及其 监管将提供一个框架，说明这些过程如何 发生在高等生物中，什么事件可能会诱发恶性肿瘤？ 正常静止细胞的生长，以及这些异常的 可以控制或阻止这些过程。

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.