The DnaA Tale.

Flemming G Hansen,Tove Atlung

doi:10.3389/fmicb.2018.00319

The DnaA Tale.

Flemming G Hansen, Tove Atlung

Open Access

https://doi.org/10.3389/fmicb.2018.00319

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Abstract

More than 50 years have passed since the presentation of the Replicon Model which states that a positively acting initiator interacts with a specific site on a circular chromosome molecule to initiate DNA replication. Since then, the origin of chromosome replication, oriC, has been determined as a specific region that carries sequences required for binding of positively acting initiator proteins, DnaA-boxes and DnaA proteins, respectively. In this review we will give a historical overview of significant findings which have led to the very detailed knowledge we now possess about the initiation process in bacteria using Escherichia coli as the model organism, but emphasizing that virtually all bacteria have DnaA proteins that interacts with DnaA boxes to initiate chromosome replication. We will discuss the dnaA gene regulation, the special features of the dnaA gene expression, promoter strength, and translation efficiency, as well as, the DnaA protein, its concentration, its binding to DnaA-boxes, and its binding of ATP or ADP. Furthermore, we will discuss the different models for regulation of initiation which have been proposed over the years, with particular emphasis on the Initiator Titration Model.

Highlights

The Replicon Model hypothesizes that to initiate DNA replication a positively acting initiator molecule interacts with a specific site, the replicator, on a circular chromosome (Figure 1; Jacob et al, 1963)
From a comparison of the dnaA2p promoter region with the mioC promoter region as well as from a closer look at the in vitro binding data (Speck et al, 1999) we suggest that the region act as having four closely spaced DnaA boxes upstream of the dnaA2p promoter region one of which requires DnaA-ATP for binding (Figure 6) and two sites, box b and box c with no homology to DnaA boxes, which requires DnaA-ATP
This study demonstrated that sequences ∼100 bp upstream of the promoter contributed to efficient titration and derepression of the dnaA-lacZ promoter

Summary

Introduction

The Replicon Model hypothesizes that to initiate DNA replication a positively acting initiator molecule interacts with a specific site, the replicator, on a circular chromosome (Figure 1; Jacob et al, 1963). The other study, using a fishing method to isolate high affinity DNA fragments, identified five loci (in addition to oriC) including datA and the mutH promoter (Roth and Messer, 1998) that was later found in the search for DARSs (DnaA Reactivating Sequences, see below; Fujimitsu and Katayama, 2004).

Results

Conclusion