scholarly journals Role of the CtrA cell cycle regulator in the bloodborne bacterial pathogen, Bartonella quintana.

2021 ◽  
Author(s):  
◽  
Robert Haydn Thomson
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Dna Replication ◽  
Binding Sites ◽  
Caulobacter Crescentus ◽  
Regulatory Regions ◽  
Bartonella Quintana ◽  
Cell Cycle Regulator ◽  
Wide Range

<p>Bartonella quintana is an important re-emerging human pathogen and the causative agent of trench fever. It utilizes a stealth invasion strategy to infect hosts and is transmitted by lice. Throughout infection it is crucial for the bacteria to maintain a tight regulation of cell division, to prevent immune detection and allow for transmission to new hosts. CtrA is an essential master cell cycle regulatory protein found in the alpha-proteobacteria. It regulates many genes, ensuring the appropriate timing of gene expression and DNA replication. In the model organism Caulobacter crescentus, it regulates 26% of cell cycle-regulated genes. CtrA has been reported to bind two specific DNA motifs in gene promoter regions, TTAAN7TTAAC, and TTAACCAT. Genes regulated by CtrA encode proteins with a wide range of activities, including initiation of DNA replication, cell division, DNA methylation, polar morphogenesis, flagellar biosynthesis, and cell wall metabolism. However, the role of the CtrA homologue in Bartonella spp. has not been investigated. In this project we aimed to make an initial characterisation of the master cell cycle regulator CtrA. This was done by identifying gene regulatory regions containing putative CtrA binding sites and testing for direct interactions via a -galactosidase assay. It was found B. quintana CtrA shared 81 % amino acid identity with its C. crescentus homologue. Within the genome of B. quintana str. Toulouse we discovered 21 genes containing putative CtrA binding sites in their regulatory regions. Of these genes we demonstrated interactions between CtrA and the promoter region of ftsE a cell division gene [1], hemS, and hbpC, two heme regulatory genes. We also found no evidence of CtrA regulating its own expression, which was unexpected because CtrA autoregulation has been demonstrated in C. crescentus.</p>

scholarly journals Role of the CtrA cell cycle regulator in the bloodborne bacterial pathogen, Bartonella quintana.

2021 ◽  
Author(s):  
◽  
Robert Haydn Thomson
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Dna Replication ◽  
Binding Sites ◽  
Caulobacter Crescentus ◽  
Regulatory Regions ◽  
Bartonella Quintana ◽  
Cell Cycle Regulator ◽  
Wide Range

<p>Bartonella quintana is an important re-emerging human pathogen and the causative agent of trench fever. It utilizes a stealth invasion strategy to infect hosts and is transmitted by lice. Throughout infection it is crucial for the bacteria to maintain a tight regulation of cell division, to prevent immune detection and allow for transmission to new hosts. CtrA is an essential master cell cycle regulatory protein found in the alpha-proteobacteria. It regulates many genes, ensuring the appropriate timing of gene expression and DNA replication. In the model organism Caulobacter crescentus, it regulates 26% of cell cycle-regulated genes. CtrA has been reported to bind two specific DNA motifs in gene promoter regions, TTAAN7TTAAC, and TTAACCAT. Genes regulated by CtrA encode proteins with a wide range of activities, including initiation of DNA replication, cell division, DNA methylation, polar morphogenesis, flagellar biosynthesis, and cell wall metabolism. However, the role of the CtrA homologue in Bartonella spp. has not been investigated. In this project we aimed to make an initial characterisation of the master cell cycle regulator CtrA. This was done by identifying gene regulatory regions containing putative CtrA binding sites and testing for direct interactions via a -galactosidase assay. It was found B. quintana CtrA shared 81 % amino acid identity with its C. crescentus homologue. Within the genome of B. quintana str. Toulouse we discovered 21 genes containing putative CtrA binding sites in their regulatory regions. Of these genes we demonstrated interactions between CtrA and the promoter region of ftsE a cell division gene [1], hemS, and hbpC, two heme regulatory genes. We also found no evidence of CtrA regulating its own expression, which was unexpected because CtrA autoregulation has been demonstrated in C. crescentus.</p>

Free, Conjugated and Bound Polyamines during the Ceil Cycle in Synchronized Cultures of Scenedesmus obliquus

1994 ◽  
Vol 49 (3-4) ◽  
pp. 181-185 ◽  
Author(s):  
Kiriakos Kotzabasis ◽  
Horst Senger
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Dna Replication ◽  
Scenedesmus Obliquus ◽  
Photosynthetic Apparatus ◽  
Membrane Systems ◽  
Additional Peak ◽  
Unicellular Green Alga ◽  
Synchronized Cultures

The levels of free, conjugated and bound polyamines (PA) were analyzed during the cell cycle of the synchronized unicellular green alga Scenedesmus obliquus. The polyamines putrescine (PUT) and spermidine (SPD) in their free and conjugated forms accumulated per cell to a maximum in the cell cycle at about the 16 th hour after onset of illumination. The polyamines bound to macromolecules and membrane systems showed an additional peak around the 8-10 th hour of the cell cycle. The possible role of the different forms of polyamines in DNA replication, mitosis, cell division and development of the photosynthetic apparatus is discussed

scholarly journals Coordination between Chromosome Replication, Segregation, and Cell Division in Caulobacter crescentus

2006 ◽  
Vol 188 (6) ◽  
pp. 2244-2253 ◽  
Author(s):  
Rasmus B. Jensen
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Dna Replication ◽  
Cytoplasmic Membrane ◽  
Caulobacter Crescentus ◽  
Chromosome Replication ◽  
Short Delay ◽  
Swarmer Cell ◽  
Initiation Of Dna Replication ◽  
Cell Transition

ABSTRACT Progression through the Caulobacter crescentus cell cycle is coupled to a cellular differentiation program. The swarmer cell is replicationally quiescent, and DNA replication initiates at the swarmer-to-stalked cell transition. There is a very short delay between initiation of DNA replication and movement of one of the newly replicated origins to the opposite pole of the cell, indicating the absence of cohesion between the newly replicated origin-proximal parts of the Caulobacter chromosome. The terminus region of the chromosome becomes located at the invaginating septum in predivisional cells, and the completely replicated terminus regions stay associated with each other after chromosome replication is completed, disassociating very late in the cell cycle shortly before the final cell division event. Invagination of the cytoplasmic membrane occurs earlier than separation of the replicated terminus regions and formation of separate nucleoids, which results in trapping of a chromosome on either side of the cell division septum, indicating that there is not a nucleoid exclusion phenotype.

scholarly journals Loss of PopZAtactivity inAgrobacterium tumefaciensby Deletion or Depletion Leads to Multiple Growth Poles, Minicells, and Growth Defects

mBio ◽  
2017 ◽  
Vol 8 (6) ◽  
Author(s):  
Romain Grangeon ◽  
John Zupan ◽  
Yeonji Jeon ◽  
Patricia C. Zambryski
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Agrobacterium Tumefaciens ◽  
Caulobacter Crescentus ◽  
Polar Growth ◽  
Growth Pole ◽  
Growth Defects ◽  
Animal Pathogens ◽  
Cell Asymmetry

ABSTRACTAgrobacterium tumefaciensgrows by addition of peptidoglycan (PG) at one pole of the bacterium. During the cell cycle, the cell needs to maintain two different developmental programs, one at the growth pole and another at the inert old pole. Proteins involved in this process are not yet well characterized. To further characterize the role of pole-organizing proteinA. tumefaciensPopZ (PopZAt), we created deletions of the five PopZAtdomains and assayed their localization. In addition, we created apopZAtdeletion strain (ΔpopZAt) that exhibited growth and cell division defects with ectopic growth poles and minicells, but the strain is unstable. To overcome the genetic instability, we created an inducible PopZAtstrain by replacing the native ribosome binding site with a riboswitch. Cultivated in a medium without the inducer theophylline, the cells look like ΔpopZAtcells, with a branching and minicell phenotype. Adding theophylline restores the wild-type (WT) cell shape. Localization experiments in the depleted strain showed that the domain enriched in proline, aspartate, and glutamate likely functions in growth pole targeting. Helical domains H3 and H4 together also mediate polar localization, but only in the presence of the WT protein, suggesting that the H3 and H4 domains multimerize with WT PopZAt, to stabilize growth pole accumulation of PopZAt.IMPORTANCEAgrobacterium tumefaciensis a rod-shaped bacterium that grows by addition of PG at only one pole. The factors involved in maintaining cell asymmetry during the cell cycle with an inert old pole and a growing new pole are not well understood. Here we investigate the role of PopZAt, a homologue ofCaulobacter crescentusPopZ (PopZCc), a protein essential in many aspects of pole identity inC. crescentus. We report that the loss of PopZAtleads to the appearance of branching cells, minicells, and overall growth defects. As many plant and animal pathogens also employ polar growth, understanding this process inA. tumefaciensmay lead to the development of new strategies to prevent the proliferation of these pathogens. In addition, studies ofA. tumefacienswill provide new insights into the evolution of the genetic networks that regulate bacterial polar growth and cell division.

scholarly journals LMO2 Regulates DNA Replication in Hematopoietic Cells

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 553-553
Author(s):  
Marie-Claude Sincennes ◽  
Magali Humbert ◽  
Benoit Grondin ◽  
Christophe Cazaux ◽  
Veronique Lisi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Cell Differentiation ◽  
Dna Replication ◽  
Cell Fate ◽  
Binding Sites ◽  
Erythroid Differentiation ◽  
S Phase

Abstract Oncogenic transcription factors are major drivers in acute leukemias. These oncogenes are believed to subvert normal cell identity via the establishment of gene expression programs that dictate cell differentiation and growth. The LMO2 oncogene, which is commonly activated in T-cell acute lymphoblastic leukemia (T-ALL), has a well-established function in transcription regulation. We and others previously demonstrated that LMO1 or LMO2 collaborate with the SCL transcription factor to activate a self-renewal program that converts non self-renewing progenitors into pre-leukemic stem cells. Here we demonstrate a non-transcriptional role of LMO2 in controlling cell fate by directly promoting DNA replication, a hitherto unrecognized mechanism that might also account for its oncogenic properties. To address the question whether LMO2 controls other functions via protein-protein interactions, we performed a proteome-wide screen for LMO2 interaction partners in Kit+ Lin- cells. In addition to known LMO2-interacting proteins such as LDB1 and to proteins associated with transcription, we unexpectedly identified new interactions with three essential DNA replication enzymes, namely minichromosome 6 (MCM6), DNA polymerase delta (POLD1) and DNA primase (PRIM1). First, we show that in Kit+ hematopoietic cells (TF-1), all components of the pre-replication complex co-immunoprecipitate with LMO2 but not with SCL, suggesting a novel SCL-independent function. Second, LMO2 is recruited to DNA replication origins in these cells together with MCM5. Third, tethering LMO2 to synthetic DNA sequences is sufficient to transform these into origins of replication. Indeed, we show by DNA capture that LMO2 fused to the DNA binding domain of GAL4 is sufficient to recruit DNA replication proteins to GAL4 binding sites on DNA. In vivo, this recruitment is sufficient to drive DNA replication in a manner which is dependent on the integrity of the GAL4 binding sites. These results provide unambiguous evidence for a role of LMO2 in directly controlling DNA replication. Cell cycle and cell differentiation are tightly coordinated during normal hematopoiesis, both during erythroid differentiation and during thymocyte development. We next addressed the functional importance of LMO2 in these two lineages. Erythroid cell differentiation proceeds through different stages from the CD71+Ter119- to the CD71-Ter119+. These stages are also distinguishable by morphological criteria. We observe that LMO2 protein levels directly correlate with the proportion of cells in S phase, i.e. both LMO2 levels and the proportions of cycling cells decrease with terminal erythroid differentiation. Strikingly, lowering LMO2 levels in fetal liver erythroid progenitors via shRNAs decreases the proportion of cells in S phase and arrests Epo-dependent cell growth. Despite a drastic decrease in the numbers of erythroid precursors, these cells differentiate readily to the CD71-Ter119+ stage. Therefore, LMO2 levels dictate cell fate in the erythroid lineage, by favoring DNA replication at the expense of terminal maturation. Conversely, ectopic expression in thymocytes induces DNA replication and drives cells into cell cycle, causing differentiation blockade. Our results define a novel role for the oncogenic transcription factor LMO2 in directly promoting DNA synthesis. To our knowledge, this is the first evidence for a non-transcriptional function of the LMO2 oncogene that drives cell cycle at the expense of differentiation, favouring progenitor cell expansion in the thymus, and causing T-ALL when ectopically expressed in the T lineage. We propose that the non-transcriptional control of DNA replication uncovered here for LMO2 may be a more common function of oncogenic transcription factors than previously appreciated. Disclosures No relevant conflicts of interest to declare.

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.

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.

scholarly journals Cell cycle constraints on capsulation and bacteriophage susceptibility

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Silvia Ardissone ◽  
Coralie Fumeaux ◽  
Matthieu Bergé ◽  
Audrey Beaussart ◽  
Laurence Théraulaz ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Steric Hindrance ◽  
Crucial Role ◽  
Caulobacter Crescentus ◽  
G1 Phase ◽  
Restriction Factor ◽  
Flagellar Motility ◽  
Alpha Proteobacteria

Despite the crucial role of bacterial capsules in pathogenesis, it is still unknown if systemic cues such as the cell cycle can control capsule biogenesis. In this study, we show that the capsule of the synchronizable model bacterium Caulobacter crescentus is cell cycle regulated and we unearth a bacterial transglutaminase homolog, HvyA, as restriction factor that prevents capsulation in G1-phase cells. This capsule protects cells from infection by a generalized transducing Caulobacter phage (φCr30), and the loss of HvyA confers insensitivity towards φCr30. Control of capsulation during the cell cycle could serve as a simple means to prevent steric hindrance of flagellar motility or to ensure that phage-mediated genetic exchange happens before the onset of DNA replication. Moreover, the multi-layered regulatory circuitry directing HvyA expression to G1-phase is conserved during evolution, and HvyA orthologues from related Sinorhizobia can prevent capsulation in Caulobacter, indicating that alpha-proteobacteria have retained HvyA activity.

scholarly journals CcrZ is a pneumococcal spatiotemporal cell cycle regulator that interacts with FtsZ and controls DNA replication by modulating the activity of DnaA

2021 ◽  
Author(s):  
Clement Gallay ◽  
Stefano Sanselicio ◽  
Mary E. Anderson ◽  
Young Min Soh ◽  
Xue Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Dna Replication ◽  
Daughter Cells ◽  
Cell Cycle Regulator ◽  
Regulator Protein ◽  
Cytoskeleton Protein ◽  
Initiation Of Dna Replication ◽  
Bacterial Cell Cycle ◽  
The Right

AbstractMost 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 by daughter cells is poorly understood. Here, we identify Cell Cycle Regulator protein interacting with FtsZ (CcrZ) as a conserved and essential protein in pneumococci and related Firmicutes such as Bacillus subtilis and Staphylococcus aureus. CcrZ 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 interacts directly with the cytoskeleton protein FtsZ, which places CcrZ in the middle of the newborn cell where the DnaA-bound origin is positioned. This work uncovers a mechanism for 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.

scholarly journals Regulation of Cell Division in Bacteria by Monitoring Genome Integrity and DNA Replication Status

2019 ◽  
Vol 202 (2) ◽  
Author(s):  
Peter E. Burby ◽  
Lyle A. Simmons
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Division ◽  
Dna Replication ◽  
Cell Cycle Progression ◽  
Genome Instability ◽  
Sos Response ◽  
Bacterial Cells ◽  
Cycle Progression ◽  
Content Type

ABSTRACT All organisms regulate cell cycle progression by coordinating cell division with DNA replication status. In eukaryotes, DNA damage or problems with replication fork progression induce the DNA damage response (DDR), causing cyclin-dependent kinases to remain active, preventing further cell cycle progression until replication and repair are complete. In bacteria, cell division is coordinated with chromosome segregation, preventing cell division ring formation over the nucleoid in a process termed nucleoid occlusion. In addition to nucleoid occlusion, bacteria induce the SOS response after replication forks encounter DNA damage or impediments that slow or block their progression. During SOS induction, Escherichia coli expresses a cytoplasmic protein, SulA, that inhibits cell division by directly binding FtsZ. After the SOS response is turned off, SulA is degraded by Lon protease, allowing for cell division to resume. Recently, it has become clear that SulA is restricted to bacteria closely related to E. coli and that most bacteria enforce the DNA damage checkpoint by expressing a small integral membrane protein. Resumption of cell division is then mediated by membrane-bound proteases that cleave the cell division inhibitor. Further, many bacterial cells have mechanisms to inhibit cell division that are regulated independently from the canonical LexA-mediated SOS response. In this review, we discuss several pathways used by bacteria to prevent cell division from occurring when genome instability is detected or before the chromosome has been fully replicated and segregated.

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