scholarly journals Control of DNA Replication Initiation by Ubiquitin

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 146 ◽  
Author(s):  
Esperanza Hernández-Carralero ◽  
Elisa Cabrera ◽  
Ignacio Alonso-de Vega ◽  
Santiago Hernández-Pérez ◽  
Veronique Smits ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Replication Initiation ◽  
Post Translational Modifications ◽  
Precise Control ◽  
Dna Replication Initiation ◽  
Fundamental Part ◽  
Initiation Of Dna Replication ◽  
The Right ◽  
Hydrolysis Of

Eukaryotic cells divide by accomplishing a program of events in which the replication of the genome is a fundamental part. To ensure all cells have an accurate copy of the genome, DNA replication occurs only once per cell cycle and is controlled by numerous pathways. A key step in this process is the initiation of DNA replication in which certain regions of DNA are marked as competent to replicate. Moreover, initiation of DNA replication needs to be coordinated with other cell cycle processes. At the molecular level, initiation of DNA replication relies, among other mechanisms, upon post-translational modifications, including the conjugation and hydrolysis of ubiquitin. An example is the precise control of the levels of the DNA replication initiation protein Cdt1 and its inhibitor Geminin by ubiquitin-mediated proteasomal degradation. This control ensures that DNA replication occurs with the right timing during the cell cycle, thereby avoiding re-replication events. Here, we review the events that involve ubiquitin signalling during DNA replication initiation, and how they are linked to human disease.

scholarly journals Polar Remodeling and Histidine Kinase Activation, Which Is Essential for Caulobacter Cell Cycle Progression, Are Dependent on DNA Replication Initiation

2010 ◽  
Vol 192 (15) ◽  
pp. 3893-3902 ◽  
Author(s):  
Antonio A. Iniesta ◽  
Nathan J. Hillson ◽  
Lucy Shapiro
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Histidine Kinase ◽  
Cell Cycle Progression ◽  
Caulobacter Crescentus ◽  
Replication Initiation ◽  
Cycle Progression ◽  
Dna Replication Initiation ◽  
Flagellar Biosynthesis ◽  
Initiation 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.

scholarly journals Activation of a signaling pathway by the physical translocation of a chromosome

2021 ◽  
Author(s):  
Mathilde Guzzo ◽  
Allen G. Sanderlin ◽  
Lennice K. Castro ◽  
Michael T. Laub
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Dna Replication ◽  
Signaling Pathway ◽  
Chromosome Segregation ◽  
Caulobacter Crescentus ◽  
Replication Initiation ◽  
Dna Replication Initiation ◽  
Cellular Processes ◽  
Initiation Of Dna Replication

AbstractIn every organism, the cell cycle requires the execution of multiple cellular processes in a strictly defined order. However, the mechanisms used to ensure such order remain poorly understood, particularly in bacteria. Here, we show that the activation of the essential CtrA signaling pathway that triggers cell division in Caulobacter crescentus is intrinsically coupled to the successful initiation of DNA replication via the physical translocation of a newly-replicated chromosome, powered by the ParABS system. We demonstrate that ParA accumulation at the new cell pole during chromosome segregation recruits ChpT, an intermediate component of the CtrA signaling pathway. ChpT is normally restricted from accessing the selective PopZ polar microdomain until the new chromosome and ParA arrive. Consequently, any disruption to DNA replication initiation prevents the recruitment of ChpT and, in turn, cell division. Collectively, our findings reveal how major cell-cycle events are coordinated in Caulobacter and, importantly, how the physical translocation of a chromosome triggers an essential signaling pathway.

A Novel Fluorescence-Based Screen for Inhibitors of the Initiation of DNA Replication in Bacteria

2019 ◽  
Vol 16 (3) ◽  
pp. 272-277 ◽  
Author(s):  
Rasmus N. Klitgaard ◽  
Anders Løbner-Olesen
Keyword(s):  
Dna Replication ◽  
High Throughput ◽  
Cyclic Peptide ◽  
Replication Initiation ◽  
False Positive Result ◽  
Over Expression ◽  
Initiator Protein ◽  
Dna Replication Initiation ◽  
Cellular Processes ◽  
Initiation Of Dna Replication

Background:One of many strategies to overcome antibiotic resistance is the discovery of compounds targeting cellular processes, which have not yet been exploited.Materials and Methods:Using various genetic tools, we constructed a novel high throughput, cellbased, fluorescence screen for inhibitors of chromosome replication initiation in bacteria.Results:The screen was validated by expression of an intra-cellular cyclic peptide interfering with the initiator protein DnaA and by over-expression of the negative initiation regulator SeqA. We also demonstrated that neither tetracycline nor ciprofloxacin triggers a false positive result. Finally, 400 extracts isolated mainly from filamentous actinomycetes were subjected to the screen.Conclusion:We concluded that the presented screen is applicable for identifying putative inhibitors of DNA replication initiation in a high throughput setup.

scholarly journals Archaeal Orc1 protein interacts with T-rich single-stranded DNA

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Katarzyna Wegrzyn ◽  
Igor Konieczny
Keyword(s):  
Dna Replication ◽  
Replication Initiation ◽  
Single Stranded Dna ◽  
Dna Replication Initiation ◽  
Double Stranded Dna ◽  
Nucleoprotein Complexes ◽  
Eukaryotic Organisms ◽  
Replication Initiation Proteins ◽  
Hydrolysis Of ◽  
Replication Activity

Abstract Objective The ability to form nucleoprotein complexes is a fundamental activity of DNA replication initiation proteins. They bind within or nearby the region of replication origin what results in melting of a double-stranded DNA (dsDNA) and formation of single-stranded DNA (ssDNA) region where the replication machinery can assemble. For prokaryotic initiators it was shown that they interact with the formed ssDNA and that this interaction is required for the replication activity. The ability to interact with ssDNA was also shown for Saccharomyces cerevisiae replication initiation protein complex ORC. For Archaea, which combine features of both prokaryotic and eukaryotic organisms, there was no evidence whether DNA replication initiators can interact with ssDNA. We address this issue in this study. Results Using purified Orc1 protein from Aeropyrum pernix (ApOrc1) we analyzed its ability to interact with ssDNA containing sequence of an AT-rich region of the A. pernix origin Ori1 as well as with homopolymers of thymidine (polyT) and adenosine (polyA). The Bio-layer interferometry, surface plasmon resonance and microscale thermophoresis showed that the ApOrc1 can interact with ssDNA and it binds preferentially to T-rich ssDNA. The hydrolysis of ATP is not required for this interaction.

scholarly journals Feedback Control of DnaA-Mediated Replication Initiation by Replisome-Associated HdaA Protein in Caulobacter

2009 ◽  
Vol 191 (18) ◽  
pp. 5706-5716 ◽  
Author(s):  
Justine Collier ◽  
Lucy Shapiro
Keyword(s):  
Escherichia Coli ◽  
Cell Cycle ◽  
Regulatory Mechanism ◽  
Caulobacter Crescentus ◽  
Replication Initiation ◽  
Dnaa Protein ◽  
Additional Layer ◽  
Initiation Of Dna Replication ◽  
The Right ◽  
Feedback Regulatory Mechanism

ABSTRACT Chromosome replication in Caulobacter crescentus is tightly regulated to ensure that initiation occurs at the right time and only once during the cell cycle. The timing of replication initiation is controlled by both CtrA and DnaA. CtrA binds to and silences the origin. Upon the clearance of CtrA from the cell, the DnaA protein accumulates and allows loading of the replisome at the origin. Here, we identify an additional layer of replication initiation control that is mediated by the HdaA protein. In Escherichia coli, the Hda protein inactivates DnaA after replication initiation. We show that the Caulobacter HdaA homologue is necessary to restrict the initiation of DNA replication to only once per cell cycle and that it dynamically colocalizes with the replisome throughout the cell cycle. Moreover, the transcription of hdaA is directly activated by DnaA, providing a robust feedback regulatory mechanism that adjusts the levels of HdaA to inactivate DnaA.

scholarly journals Cell Cycle-Dependent Switch of TopBP1 Functions by Cdk2 and Akt

2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Kang Liu ◽  
Joshua D. Graves ◽  
Yu-Ju Lee ◽  
Fang-Tsyr Lin ◽  
Weei-Chin Lin
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Cancer Cells ◽  
Cyclin A ◽  
Replication Initiation ◽  
Dna Replication Initiation ◽  
Cycle Dependent

ABSTRACT Cdk2-dependent TopBP1-treslin interaction is critical for DNA replication initiation. However, it remains unclear how this association is terminated after replication initiation is finished. Here, we demonstrate that phosphorylation of TopBP1 by Akt coincides with cyclin A activation during S and G2 phases and switches the TopBP1-interacting partner from treslin to E2F1, which results in the termination of replication initiation. Premature activation of Akt in G1 phase causes an early switch and inhibits DNA replication. TopBP1 is often overexpressed in cancer and can bypass control by Cdk2 to interact with treslin, leading to enhanced DNA replication. Consistent with this notion, reducing the levels of TopBP1 in cancer cells restores sensitivity to a Cdk2 inhibitor. Together, our study links Cdk2 and Akt pathways to the control of DNA replication through the regulation of TopBP1-treslin interaction. These data also suggest an important role for TopBP1 in driving abnormal DNA replication in cancer.

scholarly journals Spatio-temporal control of DNA replication by the pneumococcal cell cycle regulator CcrZ

2019 ◽  
Author(s):  
Clement Gallay ◽  
Stefano Sanselicio ◽  
Mary E. Anderson ◽  
Young Min Soh ◽  
Xue Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Dna Replication ◽  
Cell Cycle Regulator ◽  
Regulator Protein ◽  
Cytoskeleton Protein ◽  
Initiation Of Dna Replication ◽  
Spatio Temporal ◽  
Bacterial Cell Cycle ◽  
The Right

SummaryMost bacteria replicate and segregate their DNA concomitantly while growing, before cell division takes place. How bacteria synchronize these different cell cycle events to ensure faithful chromosome inheritance is poorly understood. Here, we identified a conserved and essential protein in pneumococci and related Firmicutes named CcrZ (for Cell Cycle Regulator protein interacting with FtsZ) that couples cell division with DNA replication by controlling the activity of the master initiator of DNA replication, DnaA. The absence of CcrZ causes mis-timed and reduced initiation of DNA replication, which subsequently results in aberrant cell division. We show that CcrZ from Streptococcus pneumoniae directly interacts with the cytoskeleton protein FtsZ to place it in the middle of the newborn cell where the DnaA-bound origin is positioned. Together, this work uncovers a new mechanism for the control of the bacterial cell cycle in which CcrZ controls DnaA activity to ensure that the chromosome is replicated at the right time during the cell cycle.

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