title: DnaA couples DNA replication and the expression of two cell cycle master regulators.
abstract: Cell cycle progression in Caulobacter is driven by the master transcriptional regulators CtrA and GcrA. The cellular levels of CtrA and GcrA are temporally and spatially out-of-phase during the cell cycle, with CtrA repressing gcrA transcription and GcrA activating ctrA transcription. Here, we show that DnaA, a protein required for the initiation of DNA replication, also functions as a transcriptional activator of gcrA, which in turn activates multiple genes, notably those involved in chromosome replication and segregation. The cellular concentration of DnaA is cell cycle-controlled, peaking at the time of replication initiation and gcrA induction. Regulated proteolysis of GcrA contributes to the cell cycle variations in GcrA abundance. We propose that DnaA couples DNA replication initiation with the expression of the two oscillating regulators GcrA and CtrA and that the DnaA/GcrA/CtrA regulatory cascade drives the forward progression of the Caulobacter cell cycle.
authors.affiliation: Department of Developmental Biology, School of Medicine, Stanford University Medical Center, Beckman Center, Stanford, CA 94305, USA.
authors.forename: Justine
authors.initials: J
authors.lastname: Collier
authors.forename: Sean Richard
authors.initials: SR
authors.lastname: Murray
authors.forename: Lucy
authors.initials: L
authors.lastname: Shapiro
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D001483:Base Sequence; D016935:Caulobacter crescentus / Q000378:metabolism / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology*; D004261:DNA Replication / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006207:Half-Life; D015151:Immunoblotting; D008954:Models, Biological; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; C097706:CtrA protein, Caulobacter; D004268:DNA-Binding Proteins; C066312:DnaA protein, Bacteria; D014157:Transcription Factors