DciA directs bidirectional replication initiation – 4Ds

Replication is initiated bidirectionally in all living organisms, although some replications continue unidirectionally. This implicitly raises the question of why replication must be initiated bidirectionally. Bidirectional replication initiation depends on the loading in opposite orientation of two replicative helicases at an origin of replication, onto which two replication machineries will be assembled. In bacteria, it has been proposed that the loading of replicative helicases is absolutely dependent on a co-helicase. However, in vivo data from the 4Ds consortium show that the Vibrio cholerae replicative helicase can load itself at the origin of replication of the two chromosomes of the bacterium in the absence of its co-helicase, DciA, a representative of the ancestral and major co-helicase of bacteria. We further found that in absence of DciA, replication is initiated unidirectionally and specifically on the left side of the origin of replication of chromosome 1, causing a cascade of pathological events that ultimately results in the complete degradation of chromosome 1. These observations suggest that DciA is crucial for bidirectional replication initiation.

4Ds is divided into two main tasks. Task 1 aims to describe and understand the consequences of unidirectional replication initiation on the replication program by dissecting step by step the chaos caused by the absence of DciA, from replication initiation to the complete degradation of chromosome 1. The goal of Task 2 is to decipher how and with which factors replicative co-helicases ensure bidirectional replication initiation in bacteria.
4Ds will bring together 4 partners who will combine their expertise in single molecule assays, molecular genetics, evolutionary and genomic approaches and methodologies to address these questions.