Caulobacter crescentus
            β sliding clamp employs a noncanonical regulatory model of DNA replication

ABSTRACT Caulobacter crescentus initiates a single round of DNA replication during each cell cycle. Following the initiation of DNA replication, the essential CckA histidine kinase is activated by phosphorylation, which (via the ChpT phosphotransferase) enables the phosphorylation and activation of the CtrA global regulator. CtrA∼P then blocks the reinitiation of replication while regulating the transcription of a large number of cell cycle-controlled genes. It has been shown that DNA replication serves as a checkpoint for flagellar biosynthesis and cell division and that this checkpoint is mediated by the availability of active CtrA. Because CckA∼P promotes the activation of CtrA, we addressed the question of what controls the temporal activation of CckA. We found that the initiation of DNA replication is a prerequisite for remodeling the new cell pole, which includes the localization of the DivL protein kinase to that pole and, consequently, the localization, autophosphorylation, and activation of CckA at that pole. Thus, CckA activation is dependent on polar remodeling and a DNA replication initiation checkpoint that is tightly integrated with the polar phospho-signaling cascade governing cell cycle progression.

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Competition of bacteriophage polypeptides with native replicase proteins for binding to the DNA sliding clamp reveals a novel mechanism for DNA replication arrest in Staphylococcus aureus

Molecular Microbiology ◽

10.1111/j.1365-2958.2006.05427.x ◽

2006 ◽

Vol 62 (4) ◽

pp. 1132-1143 ◽

Cited By ~ 14

Author(s):

Adam Belley ◽

Mario Callejo ◽

Francis Arhin ◽

Mohammed Dehbi ◽

Ibtihal Fadhil ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Dna Replication ◽

Sliding Clamp ◽

Replication Arrest ◽

Replicase Proteins

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The β-sliding clamp directs the localization of HdaA to the replisome in Caulobacter crescentus

Microbiology ◽

10.1099/mic.0.068577-0 ◽

2013 ◽

Vol 159 (Pt_11) ◽

pp. 2237-2248 ◽

Cited By ~ 17

Author(s):

Carmen Fernandez-Fernandez ◽

Karin Grosse ◽

Victor Sourjik ◽

Justine Collier

Keyword(s):

Caulobacter Crescentus ◽

Sliding Clamp

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A nascent polypeptide sequence modulates DnaA translation elongation in response to nutrient availability

10.1101/2021.03.31.437742 ◽

2021 ◽

Author(s):

Michele Felletti ◽

Cedric Romilly ◽

E. Gerhart H. Wagner ◽

Kristina Jonas

Keyword(s):

Dna Replication ◽

Nutrient Availability ◽

Caulobacter Crescentus ◽

Replication Initiation ◽

Peptide Sequence ◽

Synthesis Rate ◽

Translational Efficiency ◽

General Strategy ◽

Translation Elongation ◽

Nascent Chain

ABSTRACTThe ability to regulate DNA replication initiation in response to changing nutrient conditions is an important feature of most cell types. In bacteria, DNA replication is triggered by the initiator protein DnaA, which has long been suggested to respond to nutritional changes, nevertheless the underlying mechanisms remain poorly understood. Here, we report a novel mechanism that adjusts DnaA synthesis in response to nutrient availability in Caulobacter crescentus. By performing a detailed biochemical and genetic analysis of the dnaA mRNA we identified a sequence downstream of the dnaA start codon that inhibits DnaA translation elongation upon carbon exhaustion. Our data show that the corresponding peptide sequence, but not the mRNA secondary structure or the codon choice, are critical for this response, suggesting that specific amino acids in the growing DnaA nascent chain tune translational efficiency. Our study provides new insights into DnaA regulation and highlights the importance of translation elongation as a regulatory target. We propose that nascent chain sequences, like the one described, might constitute a general strategy for modulating the synthesis rate of specific proteins under changing conditions.

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