General Features of Eukaryotic DNA Replication

Unlike the genomes in bacteria and plasmids (as well as in mitochondria and chloroplasts) which consist of a circular duplex DNA, with a single ori sequence, the genomes of eukaryotes are not only much larger and linear, but also contain multiple ori sequences for DNA replication and thus multiple replicons. Thousands of replicons are simultaneously fired in mammalian genomes, as is needed to complete replication of the genome in a few hours. Mammalian genomes are three orders of magnitudes larger than the E. coli genome for which one round of replication requires about 40 min at 37°C. Replication of a mammalian genome, initiated at a single ori,would thus take more than 1 week with the same rate of synthesis. In fact, it would be even longer because the rate of DNA chain elongation is slower in eukaryotes than in E. coli, possibly because of the increased complexity of eukaryotic chromatin.

As mentioned earlier, DNA replication in eukaryotes occurs only during the S phase, which can last for several hours but whose duration varies with the organism, the cell type, and also the developmental stage. For example, in a rapidly growing early embryo of the fruitfly D. melanogaster, cellular multiplication with duplication of the complete genome occurs in less than 15 min. The details of temporal regulation of firing of different replicons are not known. However, euchromatin regions are replicated earlier than the heterochromatin regions.

The details of initiation of replication at individual replicons have not been elucidated in eukaryotes. Some ori sequences of the yeast genome, known as autonomous replication sequences (ARS), have been determined. Although such sequences in the mammalian genomes have not been isolated, the ori regions of certain genes which could be selectively amplified have been localized by twodimensional electrophoretic separation. Nevertheless, a significant amount of information has been gathered regarding regulation of DNA replication at the global level.