title: Modularity of the bacterial cell cycle enables independent spatial and temporal control of DNA replication.
abstract: BACKGROUND
  Complex regulatory circuits in biology are often built of simpler subcircuits or modules. In most cases, the functional consequences and evolutionary origins of modularity remain poorly defined.
  
  
  RESULTS
  Here, by combining single-cell microscopy with genetic approaches, we demonstrate that two separable modules independently govern the temporal and spatial control of DNA replication in the asymmetrically dividing bacterium Caulobacter crescentus. DNA replication control involves DnaA, which promotes initiation, and CtrA, which silences initiation. We show that oscillations in DnaA activity dictate the periodicity of replication while CtrA governs the asymmetric replicative fates of daughter cells. Importantly, we demonstrate that DnaA activity oscillates independently of CtrA.
  
  
  CONCLUSIONS
  The genetic separability of spatial and temporal control modules in Caulobacter reflects their evolutionary history. DnaA is the central component of an ancient and phylogenetically widespread circuit that governs replication periodicity in Caulobacter and most other bacteria. By contrast, CtrA, which is found only in the asymmetrically dividing α-proteobacteria, was integrated later in evolution to enforce replicative asymmetry on daughter cells.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Jonas
authors.forename: Y Erin
authors.initials: YE
authors.lastname: Chen
authors.forename: Michael T
authors.initials: MT
authors.lastname: Laub
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism / Q000502:physiology; D005075:Biological Evolution; D016935:Caulobacter crescentus / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D010507:Periodicity; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; C097706:CtrA protein, Caulobacter; D004268:DNA-Binding Proteins; C066312:DnaA protein, Bacteria; D014157:Transcription Factors