Abstract
Chromosome replication in Escherichia coli is initiated from a single origin, oriC. Initiation involves a number of DNA binding proteins, but only DnaA is essential and specific for the initiation process. DnaA is an AAA+ protein that binds both ATP and ADP with similar high affinities. DnaA associated with either ATP or ADP binds to a set of strong DnaA binding sites in oriC, whereas only DnaAATP is capable of binding additional and weaker sites to promote initiation. Additional DNA binding proteins act to ensure that initiation occurs timely by affecting either the cellular mass at which DNA replication is initiated, or the time window in which all origins present in a single cell are initiated, i.e. initiation synchrony, or both. Overall, these DNA binding proteins modulate the initiation frequency from oriC by: (i) binding directly to oriC to affect DnaA binding, (ii) altering the DNA topology in or around oriC, (iii) altering the nucleotide bound status of DnaA by interacting with non-coding chromosomal sequences, distant from oriC, that are important for DnaA activity. Thus, although DnaA is the key protein for initiation of replication, other DNA-binding proteins act not only on oriC for modulation of its activity but also at additional regulatory sites to control the nucleotide bound status of DnaA. Here we review the contribution of key DNA binding proteins to the tight regulation of chromosome replication in E. coli cells.
Highlights
Section for Functional Genomics and Center for Bacterial Stress Response and Persistence, Department of Biology, University of Copenhagen, Copenhagen, Denmark
DnaAATP is converted to DnaAADP primarily by a process called regulatory inactivation of DnaA (RIDA), which is dependent on the Hda protein bound to ADP and the DNA-loaded β-clamp of the polymerase III holoenzyme (Kato and Katayama, 2001), and by the less efficient datA-dependent DnaAATP hydrolysis (DDAH)
Loss of DARS2 increases the relative duration of the initiation period, leading to initiation asynchrony (Figure 2F; Fujimitsu et al, 2009; Frimodt-Moller et al, 2015). This suggests that both DARS1 and DARS2 are important for coupling initiation to cell mass increase, whereas only the cell-cycle regulated DARS2 is crucial for maintaining initiation synchrony
Summary
Chromosome replication in Escherichia coli is initiated from a single origin, oriC. Initiation involves a number of DNA binding proteins, but only DnaA is essential and specific for the initiation process. DnaA is the key protein for initiation of replication, other DNA-binding proteins act on oriC for modulation of its activity and at additional regulatory sites to control the nucleotide bound status of DnaA. DnaAATP is converted to DnaAADP primarily by a process called regulatory inactivation of DnaA (RIDA), which is dependent on the Hda protein bound to ADP and the DNA-loaded β-clamp of the polymerase III holoenzyme (Kato and Katayama, 2001), and by the less efficient datA-dependent DnaAATP hydrolysis (DDAH). DDAH takes place at datA and is dependent on IHF (Figure 1; Kasho and Katayama, 2013)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
