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Regulation of the bacterial cell cycle by an integrated genetic circuit

Author

Listed:
  • Emanuele G. Biondi

    (Harvard University
    Massachusetts Institute of Technology)

  • Sarah J. Reisinger

    (University of California)

  • Jeffrey M. Skerker

    (Harvard University
    Massachusetts Institute of Technology)

  • Muhammad Arif

    (Harvard University)

  • Barrett S. Perchuk

    (Harvard University
    Massachusetts Institute of Technology)

  • Kathleen R. Ryan

    (University of California)

  • Michael T. Laub

    (Harvard University
    Massachusetts Institute of Technology)

Abstract

How bacteria regulate cell cycle progression at a molecular level is a fundamental but poorly understood problem. In Caulobacter crescentus, two-component signal transduction proteins are crucial for cell cycle regulation, but the connectivity of regulators involved has remained elusive and key factors are unidentified. Here we identify ChpT, an essential histidine phosphotransferase that controls the activity of CtrA, the master cell cycle regulator. We show that the essential histidine kinase CckA initiates two phosphorelays, each requiring ChpT, which lead to the phosphorylation and stabilization of CtrA. Downregulation of CckA activity therefore results in the dephosphorylation and degradation of CtrA, which in turn allow the initiation of DNA replication. Furthermore, we show that CtrA triggers its own destruction by promoting cell division and inducing synthesis of the essential regulator DivK, which feeds back to downregulate CckA immediately before S phase. Our results define a single integrated circuit whose components and connectivity can account for the cell cycle oscillations of CtrA in Caulobacter.

Suggested Citation

  • Emanuele G. Biondi & Sarah J. Reisinger & Jeffrey M. Skerker & Muhammad Arif & Barrett S. Perchuk & Kathleen R. Ryan & Michael T. Laub, 2006. "Regulation of the bacterial cell cycle by an integrated genetic circuit," Nature, Nature, vol. 444(7121), pages 899-904, December.
  • Handle: RePEc:nat:nature:v:444:y:2006:i:7121:d:10.1038_nature05321
    DOI: 10.1038/nature05321
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    Cited by:

    1. Andrea Procaccini & Bryan Lunt & Hendrik Szurmant & Terence Hwa & Martin Weigt, 2011. "Dissecting the Specificity of Protein-Protein Interaction in Bacterial Two-Component Signaling: Orphans and Crosstalks," PLOS ONE, Public Library of Science, vol. 6(5), pages 1-9, May.
    2. Mitchell Brüderlin & Raphael Böhm & Firas Fadel & Sebastian Hiller & Tilman Schirmer & Badri N. Dubey, 2023. "Structural features discriminating hybrid histidine kinase Rec domains from response regulator homologs," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Keren Lasker & Steven Boeynaems & Vinson Lam & Daniel Scholl & Emma Stainton & Adam Briner & Maarten Jacquemyn & Dirk Daelemans & Ashok Deniz & Elizabeth Villa & Alex S. Holehouse & Aaron D. Gitler & , 2022. "The material properties of a bacterial-derived biomolecular condensate tune biological function in natural and synthetic systems," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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