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 ◽  
...  

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.

Author(s):  
Clement Gallay ◽  
Stefano Sanselicio ◽  
Mary E. Anderson ◽  
Young Min Soh ◽  
Xue Liu ◽  
...  

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.


1979 ◽  
Vol 37 (1) ◽  
pp. 117-124
Author(s):  
G. Cleffmann ◽  
W.O. Reuter ◽  
H.M. Seyfert

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.


Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 146 ◽  
Author(s):  
Esperanza Hernández-Carralero ◽  
Elisa Cabrera ◽  
Ignacio Alonso-de Vega ◽  
Santiago Hernández-Pérez ◽  
Veronique Smits ◽  
...  

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.


2006 ◽  
Vol 188 (6) ◽  
pp. 2244-2253 ◽  
Author(s):  
Rasmus B. Jensen

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.


2021 ◽  
Author(s):  
Mathilde Guzzo ◽  
Allen G. Sanderlin ◽  
Lennice K. Castro ◽  
Michael T. Laub

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.


2021 ◽  
Author(s):  
◽  
Robert Haydn Thomson

<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>


2021 ◽  
Author(s):  
◽  
Robert Haydn Thomson

<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>


FEBS Letters ◽  
2005 ◽  
Vol 579 (29) ◽  
pp. 6529-6536 ◽  
Author(s):  
Shriram Nallamshetty ◽  
Martin Crook ◽  
Manfred Boehm ◽  
Takanobu Yoshimoto ◽  
Michelle Olive ◽  
...  

2019 ◽  
Vol 202 (2) ◽  
Author(s):  
Peter E. Burby ◽  
Lyle A. Simmons

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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