MECHANISMS OF ESCHERICHIA COLI CHROMOSOMAL REPLICATION

染色体复制是一种与细胞分裂密切相关的事件，是一种 每一个生物体的基本生物过程。就像许多生物化学一样 途径，这一事件在第一步，即启动 染色体复制周期。这样做的长期目标是 建议的研究是从生物化学的角度来理解 大肠埃希氏菌染色体复制的启动及其调控 这些事件是如何与其他细胞过程耦合的。具体的 建议研究的目的是集中在抑制机制上。 有条件性缺陷的DNAA基因产物，一种需要 基因外抑制物启动大肠杆菌染色体复制的研究 DNAA，采用分子生物学和酶学相结合的方法。 这项研究将提供对1)的洞察。其他可复制的酶 在启动染色体复制时与DNAA蛋白相互作用， 2)。这一过程中涉及的一系列事件；3)。替代方案 通过启动复制而发生的染色体复制机制 位于染色体起始处以外的位置。 对如此紧密的引发过程的生物化学理解 与细胞分裂有关，它是如何调节的，以及 染色体复制将进一步加深我们对这些 可能发生在高等生物体中的过程，可能会导致恶性生长 正常静止的细胞，以及最终这种异常过程是如何发生的 被控制的或被阻止的

Chromosomal duplication, an event tightly coupled to cell division, is a fundamental biological process of every organism. Like many biochemical pathways, this event is regulated at the first step, the initiation of a cycle of chromosomal replication. The long range objective of this proposed research is to understand in biochemical terms, the mechanism of initiation of Escherichia coli chromosomal replication, its regulation, and how these events are coupled to other cellular processes. The specific aims of the proposed research are to focus on the mechanism of suppression of conditionally defective dnaA gene product, a protein required for initiation of E. coli chromosomal replication, by extragenic suppressors of dnaA by using a combined approach of molecular biology and enzymology. This study will provide insight into 1). other replication enzymes which interact with dnaA protein in the initiation of chromosomal replication, 2). the series of events involved in this process, and 3). alternative mechanisms of chromosomal duplication which occur by initiating replication at sites other than at the chromosomal origin. A biochemical understanding of the initiation process which is so tightly coupled to cell division, how it is regulated, and alternative pathways of chromosomal duplication will further our understanding of how these processes may occur in higher organisms, what may cause malignant growth of normally quiescent cells, and eventually how this aberrant process can be controlled or prevented.