Regulated degradation of chromosome replication proteins DnaA and CtrA in <i>Caulobacter crescentus</i>

Gorbatyuk, Boris; Marczynski, Gregory T.

doi:10.1111/j.1365-2958.2004.04459.x

Cited by 135 publications

(196 citation statements)

References 34 publications

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“…In Caulobacter crescentus, the DnaA-dependent initiation of replication is regulated through the temporal and spatial localization of the master regulatory protein CtrA, which prevents initiation in swarmer cells by binding to conserved sites within the origin, and coordinates DNA replication with the cell cycle progression (12,13). In Bacillus subtilis, a model of Gram-positive bacteria including many human pathogens, the initiation is mediated by DnaA and involves an oriC sequence related to that of E. coli (14,15).…”

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confidence: 99%

Functional dissection of YabA, a negative regulator of DNA replication initiation in Bacillus subtilis

Noirot‐Gros

Velten

Yoshimura

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

137

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The regulation of initiation of DNA replication is crucial to ensure that the genome is replicated only once per cell cycle. In the Gram-positive bacterium Bacillus subtilis, the function of the YabA protein in initiation control was assigned based on its interaction with the DnaA initiator and the DnaN sliding clamp in the yeast two-hybrid and on the overinitiation phenotype observed in a yabA null strain. However, YabA is unrelated to known regulators of initiation and interacts with several additional proteins that could also be involved directly or not in initiation control. Here, we investigated the specific role of YabA interactions with DnaA and DnaN in initiation control by identifying single amino acid changes in YabA that disrupted solely the interaction with DnaA or DnaN. These disruptive mutations delineated specific interacting surfaces involving a Zn 2؉ -cluster structure in YabA. In B. subtilis, these YabA interaction mutations abolished both initiation control and the formation of YabA foci at the replication factory. Upon coexpression of deficient YabA mutants, mixed oligomers formed foci at the replisome and restored initiation control, indicating that YabA acts within a heterocomplex with DnaA and DnaN. In agreement, purified YabA oligomerized and formed complexes with DnaA and DnaN. These findings underscore the functional association of YabA with the replication machinery, indicating that YabA regulates initiation through coupling with the elongation of replication.DnaA ͉ DnaN ͉ Gram-positive bacteria ͉ initiation control

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mentioning

confidence: 99%

Functional dissection of YabA, a negative regulator of DNA replication initiation in Bacillus subtilis

Noirot‐Gros

Velten

Yoshimura

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

137

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“…Chez l'α-protéobactérie Caulobacter crescentus, c'est la stabilité de la protéine DnaA qui est placée sous contrôle du (p)ppGpp (Figure 2). En effet, une carence nutritive active la synthèse de l'alarmone par l'unique (p)ppGpp synthétase SpoT [7][8][9], ce qui stimule, entre autres, la dégradation protéolytique de DnaA par une protéase et, de ce fait, empêche d'initier la réplication d'ADN [8,10]. À ce jour, nous ne savons pas comment le (p)ppGpp module la protéolyse de DnaA.…”

Section: Contrôle Métabolique De La Réplication D'adn Initiation De Lunclassified

Métabolisme et cycle cellulaire, deux processus interconnectés chez les bactéries

Hallez

2016

Med Sci (Paris)

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Afin d’optimiser les chances de survie d’une cellule dans son environnement, le métabolisme et le cycle cellulaire doivent nécessairement être interconnectés. En effet, les cellules possèdent des mécanismes leur permettant, d’une part, de vérifier leur état métabolique avant d’initier l’une ou l’autre étape du cycle cellulaire souvent énergivore et, d’autre part, d’achever certaines étapes du cycle cellulaire avant d’éventuellement modifier leur métabolisme. Parce que les bactéries ne dérogent pas à cette règle, un nombre croissant d’exemples de connexions entre le métabolisme et le cycle cellulaire a émergé ces dernières années. L’identification d’enzymes métaboliques comme messagers coordonnant métabolisme et cycle cellulaire, permet d’ajouter une nouvelle dimension aux cartes métaboliques. La très grande conservation de ces mêmes cartes métaboliques, des bactéries jusqu’à l’homme, permet également d’imaginer des recherches sur les cellules tumorales qui ont un cycle cellulaire débridé et un appétit vorace.

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“…Purple: DNA methylation-state based control of DnaA synthesis that creates a logical component functionally similar to a electrical set-reset flipflop (srFF) circuit (8). Carbon or nitrogen starvation halts cell-cycle progression by accelerating DnaA proteolysis (27).…”

mentioning

confidence: 99%

“…S1) (16,25,26). Elimination of DnaA halts the cell cycle (25), and control of DnaA stability is a mechanism used to halt the C. crescentus cell cycle in response to stress (27). When C. crescentus cells are starved for carbon or nitrogen, DnaA is rapidly proteolyzed, and relief of the starvation rapidly restabilizes DnaA (27).…”

mentioning

confidence: 99%

“…Elimination of DnaA halts the cell cycle (25), and control of DnaA stability is a mechanism used to halt the C. crescentus cell cycle in response to stress (27). When C. crescentus cells are starved for carbon or nitrogen, DnaA is rapidly proteolyzed, and relief of the starvation rapidly restabilizes DnaA (27). We used model checking to assess whether this DnaA stability-dependent method of halting and restarting the cell cycle is robust by adding an additional switch in the model to modulate DnaA stability.…”

mentioning

confidence: 99%

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Architecture and inherent robustness of a bacterial cell-cycle control system

Shen

Collier

Dill

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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A closed-loop control system drives progression of the coupled stalked and swarmer cell cycles of the bacterium Caulobacter crescentus in a near-mechanical step-like fashion. The cell-cycle control has a cyclical genetic circuit composed of four regulatory proteins with tight coupling to processive chromosome replication and cell division subsystems. We report a hybrid simulation of the coupled cell-cycle control system, including asymmetric cell division and responses to external starvation signals, that replicates mRNA and protein concentration patterns and is consistent with observed mutant phenotypes. An asynchronous sequential digital circuit model equivalent to the validated simulation model was created. Formal model-checking analysis of the digital circuit showed that the cell-cycle control is robust to intrinsic stochastic variations in reaction rates and nutrient supply, and that it reliably stops and restarts to accommodate nutrient starvation. Model checking also showed that mechanisms involving methylationstate changes in regulatory promoter regions during DNA replication increase the robustness of the cell-cycle control. The hybrid cell-cycle simulation implementation is inherently extensible and provides a promising approach for development of whole-cell behavioral models that can replicate the observed functionality of the cell and its responses to changing environmental conditions. Caulobacter ͉ model ͉ regulatory circuit ͉ hybrid system ͉ symbolic model checking T he identification of regulatory pathways controlling the cell cycle of the bacterium Caulobacter crescentus has progressed to the point that an experimentally based system-level characterization of the cell-cycle control circuit is available. Aspects of the cyclical circuit that drives progression of the C. crescentus cell cycle are described in recent papers (1-5). Recent findings have identified novel mechanisms providing signals that tightly integrate the biochemical and genetic components of the core cell-cycle circuit with the 3D topology of the cell (4, 6, 7) and DNA replication (8).Many of the regulatory mechanisms and pathways in the C. crescentus cell-cycle circuit operate very rapidly so that they approximate discrete switching elements, whereas others, e.g., the transcriptional regulatory networks, operate relatively slowly. This suggested use of hybrid control analysis methods (9-13) to simulate this cell-cycle control system and formal analysis methods to analyze its properties. Hybrid control systems, by definition, include both continuous and discrete regulatory mechanisms (9). We constructed a hybrid control system simulation model and derived an equivalent asynchronous discrete circuit model from the simulation model. The analysis showed that the cell-cycle control is robust and that DNA methylation-based cell-cycle regulatory mechanisms (8) enhance robustness of the cell cycle.C. crescentus always divides asymmetrically, producing morphologically distinct daughters (Fig. 1A), so it is a model system not only for bacte...

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Regulated degradation of chromosome replication proteins DnaA and CtrA in Caulobacter crescentus

Cited by 135 publications

References 34 publications

Functional dissection of YabA, a negative regulator of DNA replication initiation in Bacillus subtilis

Functional dissection of YabA, a negative regulator of DNA replication initiation in Bacillus subtilis

Métabolisme et cycle cellulaire, deux processus interconnectés chez les bactéries

Architecture and inherent robustness of a bacterial cell-cycle control system

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