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Review
. 2009:74:55-64.
doi: 10.1101/sqb.2009.74.005. Epub 2009 Aug 17.

Dynamic chromosome organization and protein localization coordinate the regulatory circuitry that drives the bacterial cell cycle

Affiliations
Review

Dynamic chromosome organization and protein localization coordinate the regulatory circuitry that drives the bacterial cell cycle

E D Goley et al. Cold Spring Harb Symp Quant Biol. 2009.

Abstract

The bacterial cell has less internal structure and genetic complexity than cells of eukaryotic organisms, yet it is a highly organized system that uses both temporal and spatial cues to drive its cell cycle. Key insights into bacterial regulatory programs that orchestrate cell cycle progression have come from studies of Caulobacter crescentus, a bacterium that divides asymmetrically. Three global regulatory proteins cycle out of phase with one another and drive cell cycle progression by directly controlling the expression of 200 cell-cycle-regulated genes. Exploration of this system provided insights into the evolution of regulatory circuits and the plasticity of circuit structure. The temporal expression of the modular subsystems that implement the cell cycle and asymmetric cell division is also coordinated by differential DNA methylation, regulated proteolysis, and phosphorylation signaling cascades. This control system structure has parallels to eukaryotic cell cycle control architecture. Remarkably, the transcriptional circuitry is dependent on three-dimensional dynamic deployment of key regulatory and signaling proteins. In addition, dynamically localized DNA-binding proteins ensure that DNA segregation is coupled to the timing and cellular position of the cytokinetic ring. Comparison to other organisms reveals conservation of cell cycle regulatory logic, even if regulatory proteins, themselves, are not conserved.

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Figures

Figure 1.
Figure 1.
Replication initiation is limited to once per cell cycle by oscillating master regulators in both prokaryotes and eukaryotes. (A) Caulobacter cell cycle. The swarmer cell sheds its polar flagellum, and in the presence of low CtrA (red) and high DnaA (purple), DNA replication can initiate in the new stalked cell. (Colored arcs) Presence of the indicated master regulator protein, (curved ellipses) circular chromosome. (B) Generalized eukaryotic cell cycle. The APC is active from the metaphase-to-anaphase transition in late mitosis through most of G1 phase, keeping CDK–cyclin activity low and allowing loading of pre-RC complexes and origin licensing. When S-phase CDK cyclins are activated at the onset of S phase, licensed origins fire simultaneously.
Figure 2.
Figure 2.
The Caulobacter core cell cycle transcriptional control circuit includes posttranslational regulation of master regulators. Each master regulator activates transcription of the next and, in the case of CtrA and CcrM, inhibits transcription of the previous master regulator in the cascade. Promoters and genes encoding the master regulators are depicted with regulatory and/or binding motifs (small boxes) indicated. The color of the regulatory motif correlates with the master regulator that governs it (i.e., small red boxes represent CtrA-binding sites, etc.). (Asterisks) CcrM methylation sites, (bubbles) posttranslational regulation of DnaA and CtrA. (1) DnaA is inactivated after HdaA joins the replisome upon initiation of replication. (2) CtrA is localized to the stalked pole, by the concerted action of RcdA, PopA, ClpXP, and CpdR, where it is subjected to ClpXP-mediated proteolysis. (3) CtrA is phosphorylated and activated by the same CckA-ChpT phosphorelay that phosphorylates and inactivates CpdR.
Figure 3.
Figure 3.
Placement of the division site integrates positional information from the poles and the chromosomes. (A) In Caulobacter, the MipZ complex is localized at the old pole and FtsZ is observed at the new pole. Upon segregation of parS, MipZ becomes bipolar, displacing FtsZ from the pole and targeting it to mid cell. (B) In E. coli, MinCD oscillates from pole to pole driven by MinE (which moves in the direction of the purple arrows). Additionally, SlmA on the segregated chromosomes inhibits FtsZ assembly over the bulk of the nucleoid. (C) B. subtilis also uses MinCD to inhibit polymerization of FtsZ next to newly formed poles but is localized by DivIVA. The activities of the Min system are complemented by Noc, which prevents Z-ring assembly over the chromosome(s).

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