Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication

C. Lori, Shogo Ozaki, S. Steiner, R. Böhm, S. Abel, B. N. Dubey, T. Schirmer, S. Hiller, U. Jenal

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Fundamental to all living organisms is the capacity to coordinate cell division and cell differentiation to generate appropriate numbers of specialized cells. Whereas eukaryotes use cyclins and cyclin-dependent kinases to balance division with cell fate decisions, equivalent regulatory systems have not been described in bacteria. Moreover, the mechanisms used by bacteria to tune division in line with developmental programs are poorly understood. Here we show that Caulobacter crescentus, a bacterium with an asymmetric division cycle, uses oscillating levels of the second messenger cyclic diguanylate (c-di-GMP) to drive its cell cycle. We demonstrate that c-di-GMP directly binds to the essential cell cycle kinase CckA to inhibit kinase activity and stimulate phosphatase activity. An upshift of c-di-GMP during the G1-S transition switches CckA from the kinase to the phosphatase mode, thereby allowing replication initiation and cell cycle progression. Finally, we show that during division, c-di-GMP imposes spatial control on CckA to install the replication asymmetry of future daughter cells. These studies reveal c-di-GMP to be a cyclin-like molecule in bacteria that coordinates chromosome replication with cell morphogenesis in Caulobacter. The observation that c-di-GMP-mediated control is conserved in the plant pathogen Agrobacterium tumefaciens suggests a general mechanism through which this global regulator of bacterial virulence and persistence coordinates behaviour and cell proliferation.

Original languageEnglish
Pages (from-to)236-239
Number of pages4
JournalNature
Volume523
Issue number7559
DOIs
Publication statusPublished - Jul 9 2015

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Cell Cycle
Chromosomes
Bacteria
Cyclins
Phosphotransferases
Phosphoric Monoester Hydrolases
Cell Division
Caulobacter
Caulobacter crescentus
Agrobacterium tumefaciens
Cyclin-Dependent Kinases
Second Messenger Systems
Eukaryota
Morphogenesis
Virulence
bis(3',5')-cyclic diguanylic acid
Cell Differentiation
Cell Count
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • General

Cite this

Lori, C., Ozaki, S., Steiner, S., Böhm, R., Abel, S., Dubey, B. N., ... Jenal, U. (2015). Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication. Nature, 523(7559), 236-239. https://doi.org/10.1038/nature14473

Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication. / Lori, C.; Ozaki, Shogo; Steiner, S.; Böhm, R.; Abel, S.; Dubey, B. N.; Schirmer, T.; Hiller, S.; Jenal, U.

In: Nature, Vol. 523, No. 7559, 09.07.2015, p. 236-239.

Research output: Contribution to journalArticle

Lori, C, Ozaki, S, Steiner, S, Böhm, R, Abel, S, Dubey, BN, Schirmer, T, Hiller, S & Jenal, U 2015, 'Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication', Nature, vol. 523, no. 7559, pp. 236-239. https://doi.org/10.1038/nature14473
Lori C, Ozaki S, Steiner S, Böhm R, Abel S, Dubey BN et al. Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication. Nature. 2015 Jul 9;523(7559):236-239. https://doi.org/10.1038/nature14473
Lori, C. ; Ozaki, Shogo ; Steiner, S. ; Böhm, R. ; Abel, S. ; Dubey, B. N. ; Schirmer, T. ; Hiller, S. ; Jenal, U. / Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication. In: Nature. 2015 ; Vol. 523, No. 7559. pp. 236-239.
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