A Genetic Oscillator and the Regulation of Cell Cycle Progression in Caulobacter crescentus

Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
Cell cycle (Georgetown, Tex.) (Impact Factor: 4.57). 11/2004; 3(10):1252-4. DOI: 10.4161/cc.3.10.1181
Source: PubMed


Analyses of cell polarity, division, and differentiation in prokaryotes have identified several regulatory proteins that exhibit dramatic changes in expression and spatial localization over the course of a cell cycle. The dynamic behavior of these proteins is often intrinsically linked to their function as polarity determinants.(1-3) In the alpha-proteobacterium, Caulobacter crescentus, the CtrA global transcriptional regulator exhibits a spatially and temporally dynamic expression pattern across the cell cycle. CtrA plays key roles in asymmetric cell division and in the timing of chromosome replication.(3,4) An additional global regulator, GcrA, has recently been discovered that both regulates and is regulated by CtrA.(5) Together, these regulatory proteins create a genetic circuit in which the cellular concentrations of CtrA and GcrA oscillate spatially and temporally to control daughter cell differentiation and cell cycle progression.

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    • "GcrA could interact directly with the promoter DNA or alternatively, could interact with a protein bound to the promoter DNA. Since GcrA lacks any detectable functional motifs, if an interaction with DNA occurs it is likely to be via a novel mechanism (Crosson et al., 2004). If GcrA does not interact directly with DNA, the mechanism of transcriptional regulation by this protein is likely to be novel. "
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    ABSTRACT: Caulobacter crescentus has become the predominant bacterial model system to study the regulation of cell-cycle progression. Stage-specific processes such as chromosome replication and segregation, and cell division are coordinated with the development of four polar structures: the flagellum, pili, stalk, and holdfast. The production, activation, localization, and proteolysis of specific regulatory proteins at precise times during the cell cycle culminate in the ability of the cell to produce two physiologically distinct daughter cells. We examine the recent advances that have enhanced our understanding of the mechanisms of temporal and spatial regulation that occur during cell-cycle progression.
    Advances in Microbial Physiology 02/2008; 54:1-101. DOI:10.1016/S0065-2911(08)00001-5 · 3.25 Impact Factor
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    ABSTRACT: Regulated proteolysis is essential for cell cycle progression in both prokaryotes and eukaryotes. We show here that the ClpXP protease, responsible for the degradation of multiple bacterial proteins, is dynamically localized to specific cellular positions in Caulobacter where it degrades colocalized proteins. The CtrA cell cycle master regulator, that must be cleared from the Caulobacter cell to allow the initiation of chromosome replication, interacts with the ClpXP protease at the cell pole where it is degraded. We have identified a novel, conserved protein, RcdA, that forms a complex with CtrA and ClpX in the cell. RcdA is required for CtrA polar localization and degradation by ClpXP. The localization pattern of RcdA is coincident with and dependent upon ClpX localization. Thus, a dynamically localized ClpXP proteolysis complex in concert with a cytoplasmic factor provides temporal and spatial specificity to protein degradation during a bacterial cell cycle.
    Cell 02/2006; 124(3):535-47. DOI:10.1016/j.cell.2005.12.033 · 32.24 Impact Factor
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    ABSTRACT: Flagellar gene networks are fascinating, owing to their complexity - they usually coordinate the expression of more than 40 genes - and particular wiring that elicits temporal expression coupled to organelle morphogenesis. Moreover, many of the lessons learned from flagellar regulation are generally applicable to type III secretion systems. Our understanding of flagellar networks is rapidly expanding to include diverse organisms, as well as deepening to enable the development of predictive wiring diagrams. Numerous regulators control the regulation of flagella, and one of the next challenges in the field is to integrate flagellar gene control into master blueprints of global gene expression.
    Current Opinion in Microbiology 05/2006; 9(2):180-6. DOI:10.1016/j.mib.2006.02.001 · 5.90 Impact Factor
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