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Journal of Bacteriology, October 2008, p. 6867-6880, Vol. 190, No. 20
0021-9193/08/$08.00+0     doi:10.1128/JB.00700-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

SpoT Regulates DnaA Stability and Initiation of DNA Replication in Carbon-Starved Caulobacter crescentus{triangledown}

Joseph A. Lesley and Lucy Shapiro*

Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305

Received 17 May 2008/ Accepted 8 August 2008

Cell cycle progression and polar differentiation are temporally coordinated in Caulobacter crescentus. This oligotrophic bacterium divides asymmetrically to produce a motile swarmer cell that represses DNA replication and a sessile stalked cell that replicates its DNA. The initiation of DNA replication coincides with the proteolysis of the CtrA replication inhibitor and the accumulation of DnaA, the replication initiator, upon differentiation of the swarmer cell into a stalked cell. We analyzed the adaptive response of C. crescentus swarmer cells to carbon starvation and found that there was a block in both the swarmer-to-stalked cell polar differentiation program and the initiation of DNA replication. SpoT is a bifunctional synthase/hydrolase that controls the steady-state level of the stress-signaling nucleotide (p)ppGpp, and carbon starvation caused a SpoT-dependent increase in (p)ppGpp concentration. Carbon starvation activates DnaA proteolysis (B. Gorbatyuk and G. T. Marczynski, Mol. Microbiol. 55:1233-1245, 2005). We observed that SpoT is required for this phenomenon in swarmer cells, and in the absence of SpoT, carbon-starved swarmer cells inappropriately initiated DNA replication. Since SpoT controls (p)ppGpp abundance, we propose that this nucleotide relays carbon starvation signals to the cellular factors responsible for activating DnaA proteolysis, thereby inhibiting the initiation of DNA replication. SpoT, however, was not required for the carbon starvation block of the swarmer-to-stalked cell polar differentiation program. Thus, swarmer cells utilize at least two independent signaling pathways to relay carbon starvation signals: a SpoT-dependent pathway mediating the inhibition of DNA replication initiation, and a SpoT-independent pathway(s) that blocks morphological differentiation.

* Corresponding author. Mailing address: Beckman B300, Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305. Phone: (650) 725-7678. Fax: (650) 725-7739. E-mail: shapiro{at}stanford.edu

{triangledown} Published ahead of print on 22 August 2008.

Journal of Bacteriology, October 2008, p. 6867-6880, Vol. 190, No. 20
0021-9193/08/$08.00+0     doi:10.1128/JB.00700-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Collier, J., Shapiro, L. (2009). Feedback Control of DnaA-Mediated Replication Initiation by Replisome-Associated HdaA Protein in Caulobacter. J. Bacteriol. 191: 5706-5716 [Abstract] [Full Text]  
  • Rahn-Lee, L., Gorbatyuk, B., Skovgaard, O., Losick, R. (2009). The Conserved Sporulation Protein YneE Inhibits DNA Replication in Bacillus subtilis. J. Bacteriol. 191: 3736-3739 [Abstract] [Full Text]  


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