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 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.

Periodic sensitivity of mechanisms of cytodifferentiation in cleaving eggs of Limnaea stagnalis

Development ◽  
1964 ◽  
Vol 12 (2) ◽  
pp. 183-195
Author(s):  
W. L. M. Geilenkirchen
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
Cell Division ◽  
Dna Replication ◽  
Time Course ◽  
Chromosome Doubling ◽  
Daughter Cells ◽  
Morphogenetic Factors ◽  
Limnaea Stagnalis

Investigations on cellular reproduction have led to a highly resolved and integrated picture of the cell cycle in a morphological and physiological sense. The various preparations for division, doubling of components or syntheses, follow their own time course parallel to one another. It has become evident that the various factors involved in cell division are dissociable, for example chromosome doubling and reproduction of centrioles (Bucher & Mazia, 1960), DNA replication and protein synthesis (Zeuthen, 1961). The conditions for cell division in general are applicable to division of egg cells. However, in addition in egg cells there is a complicating system of morphogenetic factors acting, as must be postulated from the observation that in ‘mosaic’ eggs the fate of the blastomeres is fixed. In dividing eggs differences between daughter cells may be due to local differences established during oögenesis in the mother which are parcelled out during cleavages.

Increase in macromolecular amounts during the cell cycle of Tetrahymena: a contribution to cell cycle control

1979 ◽  
Vol 37 (1) ◽  
pp. 117-124
Author(s):  
G. Cleffmann ◽  
W.O. Reuter ◽  
H.M. Seyfert
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Dna Replication ◽  
Protein Content ◽  
Cell Size ◽  
Cell Cycle Control ◽  
Negative Control ◽  
Dna Amount ◽  
Protein Ratio ◽  
Initiation Of Dna Replication

Increases in RNA, protein and cell size were determined cytophotometrically during the cell division cycle of Tetrahymena. For these parameters different patterns were found. RNA accumulates slowly during G1 period and faster during macronuclear S. This agrees with the changing uridine incorporation rate which is at least partly related to the varying macronuclear DNA amount. Increases in protein content and cell size occur mainly during G1 and G2. This pattern was confirmed by determining the RNA: protein ratio in individual cells. It is minimal at the end of the G1 period. These findings and evidence from the literature suggest that initiation of DNA replication is under negative control by the relative RNA content of the cell.

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 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 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 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>

scholarly journals The cell cycle regulator p27Kip1interacts with MCM7, a DNA replication licensing factor, to inhibit initiation of DNA replication

FEBS Letters ◽  
2005 ◽  
Vol 579 (29) ◽  
pp. 6529-6536 ◽  
Author(s):  
Shriram Nallamshetty ◽  
Martin Crook ◽  
Manfred Boehm ◽  
Takanobu Yoshimoto ◽  
Michelle Olive ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Cell Cycle Regulator ◽  
Licensing Factor ◽  
Initiation Of Dna Replication

scholarly journals DNA replication and mitotic entry: A brake model for cell cycle progression

2019 ◽  
Vol 218 (12) ◽  
pp. 3892-3902 ◽  
Author(s):  
Bennie Lemmens ◽  
Arne Lindqvist
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Dna Replication ◽  
Cell Cycle Progression ◽  
Genome Instability ◽  
Cycle Model ◽  
Cycle Progression ◽  
Daughter Cells ◽  
Core Function ◽  
A Cell

The core function of the cell cycle is to duplicate the genome and divide the duplicated DNA into two daughter cells. These processes need to be carefully coordinated, as cell division before DNA replication is complete leads to genome instability and cell death. Recent observations show that DNA replication, far from being only a consequence of cell cycle progression, plays a key role in coordinating cell cycle activities. DNA replication, through checkpoint kinase signaling, restricts the activity of cyclin-dependent kinases (CDKs) that promote cell division. The S/G2 transition is therefore emerging as a crucial regulatory step to determine the timing of mitosis. Here we discuss recent observations that redefine the coupling between DNA replication and cell division and incorporate these insights into an updated cell cycle model for human cells. We propose a cell cycle model based on a single trigger and sequential releases of three molecular brakes that determine the kinetics of CDK activation.

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