The replicon model and eukaryotic chromosomes

Thirty years ago, Jacob, Cuzin, and Brenner proposed the replicon model of DNA replication to describe the regulation of Escherichia coli chromosomal duplication (Jacob et al. 1964). This model predicted that a positive trans-acting protein, called the initiator, would activate DNA replication through a cis-acting sequence called the replicator. Subsequent studies demonstrated the validity of this model and identified the dnaA protein as the initiator and oriC as the replicator for replication of the E. coli chromosome (Kornberg and Baker 1991). The finding that a number of bacteriophage and eukaryotic viruses use a similar mechanism to replicate their genomes supports the generality of this model (Challberg and Kelly 1989; Stillman 1989). In eukaryotic cells, the problem of chromosomal replication is much more complex. Instead of a single origin of replication, hundreds of origins must be coordinately regulated. In addition, the timing and extent of replication are precisely controlled during the..