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Journal of Bacteriology, September 2009, p. 5706-5716, Vol. 191, No. 18
0021-9193/09/$08.00+0     doi:10.1128/JB.00525-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Feedback Control of DnaA-Mediated Replication Initiation by Replisome-Associated HdaA Protein in Caulobacter{triangledown}

Justine Collier1* and Lucy Shapiro2

Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Quartier UNIL/Sorge, Lausanne, CH 1015, Switzerland,1 Department of Developmental Biology, School of Medicine, Beckman Center, Stanford University, Stanford, California 943052

Received 20 April 2009/ Accepted 14 July 2009

Chromosome replication in Caulobacter crescentus is tightly regulated to ensure that initiation occurs at the right time and only once during the cell cycle. The timing of replication initiation is controlled by both CtrA and DnaA. CtrA binds to and silences the origin. Upon the clearance of CtrA from the cell, the DnaA protein accumulates and allows loading of the replisome at the origin. Here, we identify an additional layer of replication initiation control that is mediated by the HdaA protein. In Escherichia coli, the Hda protein inactivates DnaA after replication initiation. We show that the Caulobacter HdaA homologue is necessary to restrict the initiation of DNA replication to only once per cell cycle and that it dynamically colocalizes with the replisome throughout the cell cycle. Moreover, the transcription of hdaA is directly activated by DnaA, providing a robust feedback regulatory mechanism that adjusts the levels of HdaA to inactivate DnaA.

* Corresponding author. Mailing address: Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Quartier UNIL/Sorge, Lausanne, CH 1015, Switzerland. Phone: 41 21 692 5610. Fax: 41 21 692 5605. E-mail: Justine.collier{at}unil.ch

{triangledown} Published ahead of print on 24 July 2009.

Journal of Bacteriology, September 2009, p. 5706-5716, Vol. 191, No. 18
0021-9193/09/$08.00+0     doi:10.1128/JB.00525-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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