12 Temporal Order of DNA Replication

Abstract

THE REPLICATION CLOCK
In every organism, DNA replication takes place in an ordered physical and temporal fashion. Although this process is primarily necessary to carry out the task of copying the genome, it may also indirectly play a role in the regulation of gene expression. In Escherichia coli, for example, the entire 4-Mb circular chromosome undergoes bidirectional DNA synthesis that is initiated from a single origin. It takes at least 40 minutes to copy the complete bacterial genome, and as a result, genes located near the origin are replicated early in the cell cycle whereas those positioned at the opposite end of the chromosome are synthesized late in the cycle. One direct consequence of this temporal organization is that in rapidly dividing cells, the early-replicating genes themselves accumulate differentially in high copy number (von Meyenburg and Hansen 1987), and this most certainly has profound effects on the overall expression pattern of the organism.

Compared to prokaryotes, eukaryotic organisms contain a much larger genome. Although the total DNA is divided into separate chromosome molecules, each of these entities in itself carries a considerable amount of genetic information, and DNA synthesis is accomplished through the action of multiple bidirectional origins. If all of these replication units were activated simultaneously, the entire process of replication could be completed very quickly. However, replication starts are actually distributed in a programmed manner throughout the length of S phase, and, as a consequence, each origin is turned on at a specific time. In the yeast Saccharomyces...