by Christoph Weigel
Figure 1. 'Circles in the Sand'. Source.
Sixty years ago Jacob, Brenner and Cuzin devised their 'Replicon Model', inspiring and useful guideline for replication research ever since. According to the model, a 'Replicon' is a genetic element replicated from a single 'Replicator'—replication origin, in modern terms—and replication is triggered by a positive trans-acting factor, the 'Initiator' (see the sketch). One hallmark of the 'Replicon Model' was the postulation of a positive regulator: at the time of its publication gene regulation was mostly thought about in terms of negative regulation or repression, inspired by the seminal Lac operon paradigm.
A Matter of Language
Many bacteria have a single chromosomal replication origin, oriC, which has been identified and studied in E. coli (Gammaproteobacteria), Bacillus subtilis (Firmicutes), Caulobactder crescentus (Alphaproteobacteria), Helicobacter pylori (Epsilonproteobateria), Mycobacterium tuberculosis and Streptomyces coelicolor (Actinomycetes), to name just some favored model organisms. The 'Initiator' in bacteria is the DnaA protein. All sequenced bacterial genomes have dnaA genes and all DnaA proteins are homologs that belong to a distinct subclass of the AAA+ ATPases. All bacteria employ a set of conserved replication factors for initiation, strand separation, priming, clamping, and discontinuous DNA synthesis. Despite this relative simplicity, the pre- and post-initiation mechanisms that ensure the 'once and only once' chromosome replication per cell cycle turned out to be not only intricate but astonishingly variable among the cases studied. Using a metaphor one might say that with respect to replication, all bacteria speak English, using the same grammar and syntax but each branch with a rather unique local dialect in their vocabulary. Just like a guy from Inverness, Florida would face problems getting along in Inverness, Scotland.