scholarly journals The Ribbon-Helix-Helix Domain Protein CdrS Regulates the Tubulin Homolog ftsZ2 To Control Cell Division in Archaea

mBio ◽  
2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Cynthia L. Darnell ◽  
Jenny Zheng ◽  
Sean Wilson ◽  
Ryan M. Bertoli ◽  
Alexandre W. Bisson-Filho ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Growth ◽  
Transcriptional Control ◽  
Control Cell ◽  
Time Lapse ◽  
Live Cells ◽  
Central Function ◽  
Individual Organism ◽  
Healthy Cell

ABSTRACT Precise control of the cell cycle is central to the physiology of all cells. In prior work we demonstrated that archaeal cells maintain a constant size; however, the regulatory mechanisms underlying the cell cycle remain unexplored in this domain of life. Here, we use genetics, functional genomics, and quantitative imaging to identify and characterize the novel CdrSL gene regulatory network in a model species of archaea. We demonstrate the central role of these ribbon-helix-helix family transcription factors in the regulation of cell division through specific transcriptional control of the gene encoding FtsZ2, a putative tubulin homolog. Using time-lapse fluorescence microscopy in live cells cultivated in microfluidics devices, we further demonstrate that FtsZ2 is required for cell division but not elongation. The cdrS-ftsZ2 locus is highly conserved throughout the archaeal domain, and the central function of CdrS in regulating cell division is conserved across hypersaline adapted archaea. We propose that the CdrSL-FtsZ2 transcriptional network coordinates cell division timing with cell growth in archaea. IMPORTANCE Healthy cell growth and division are critical for individual organism survival and species long-term viability. However, it remains unknown how cells of the domain Archaea maintain a healthy cell cycle. Understanding the archaeal cell cycle is of paramount evolutionary importance given that an archaeal cell was the host of the endosymbiotic event that gave rise to eukaryotes. Here, we identify and characterize novel molecular players needed for regulating cell division in archaea. These molecules dictate the timing of cell septation but are dispensable for growth between divisions. Timing is accomplished through transcriptional control of the cell division ring. Our results shed light on mechanisms underlying the archaeal cell cycle, which has thus far remained elusive.

scholarly journals The ribbon-helix-helix domain proteins CdrS and CdrL regulate cell division in archaea

2020 ◽  
Author(s):  
Cynthia L. Darnell ◽  
Jenny Zheng ◽  
Sean Wilson ◽  
Ryan M. Bertoli ◽  
Alexandre W. Bisson-Filho ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Growth ◽  
Transcriptional Control ◽  
Quantitative Imaging ◽  
Time Lapse ◽  
Live Cells ◽  
Central Function ◽  
Individual Organism ◽  
Healthy Cell

AbstractPrecise control of the cell cycle is central to the physiology of all cells. In prior work we demonstrated that archaeal cells maintain a constant size; however, the regulatory mechanisms underlying the cell cycle remain unexplored in this domain of life. Here we use genetics, functional genomics, and quantitative imaging to identify and characterize the novel CdrSL gene regulatory network in a model species of archaea. We demonstrate the central role of these ribbon-helix-helix family transcription factors in the regulation of cell division through specific transcriptional control of the gene encoding FtsZ2, a putative tubulin homolog. Using time lapse fluorescence microscopy in live cells cultivated in microfluidics devices, we further demonstrate that FtsZ2 is required for cell division but not elongation. The cdrS-ftsZ2 locus is highly conserved throughout the archaeal domain, and the central function of CdrS in regulating cell division is conserved across hypersaline adapted archaea. We propose that the CdrSL-FtsZ2 transcriptional network coordinates cell division timing with cell growth in archaea.ImportanceHealthy cell growth and division are critical for individual organism survival and species long-term viability. However, it remains unknown how cells of the domain Archaea maintain a healthy cell cycle. Understanding archaeal cell cycle is of paramount evolutionary importance given that an archaeal cell was the host of the endosymbiotic event that gave rise to eukaryotes. Here we identify and characterize novel molecular players needed for regulating cell division in archaea. These molecules dictate the timing of cell septation, but are dispensable for growth between divisions. Timing is accomplished through transcriptional control of the cell division ring. Our results shed light on mechanisms underlying the archaeal cell cycle, which has thus far remained elusive.

scholarly journals Noc Corrals Migration of FtsZ Protofilaments during Cytokinesis in Bacillus subtilis

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuanchen Yu ◽  
Jinsheng Zhou ◽  
Frederico J. Gueiros-Filho ◽  
Daniel B. Kearns ◽  
Stephen C. Jacobson
Keyword(s):  
Bacillus Subtilis ◽  
Cell Division ◽  
Fluorescence Microscopy ◽  
Control Cell ◽  
Time Lapse ◽  
Ring Formation ◽  
Microfluidic Channels ◽  
Content Type ◽  
The Future ◽  
Z Ring

ABSTRACT Bacteria that divide by binary fission form FtsZ rings at the geometric midpoint of the cell between the bulk of the replicated nucleoids. In Bacillus subtilis, the DNA- and membrane-binding Noc protein is thought to participate in nucleoid occlusion by preventing FtsZ rings from forming over the chromosome. To explore the role of Noc, we used time-lapse fluorescence microscopy to monitor FtsZ and the nucleoid of cells growing in microfluidic channels. Our data show that Noc does not prevent de novo FtsZ ring formation over the chromosome nor does Noc control cell division site selection. Instead, Noc corrals FtsZ at the cytokinetic ring and reduces migration of protofilaments over the chromosome to the future site of cell division. Moreover, we show that FtsZ protofilaments travel due to a local reduction in ZapA association, and the diffuse FtsZ rings observed in the Noc mutant can be suppressed by ZapA overexpression. Thus, Noc sterically hinders FtsZ migration away from the Z-ring during cytokinesis and retains FtsZ at the postdivisional polar site for full disassembly by the Min system. IMPORTANCE In bacteria, a condensed structure of FtsZ (Z-ring) recruits cell division machinery at the midcell, and Z-ring formation is discouraged over the chromosome by a poorly understood phenomenon called nucleoid occlusion. In B. subtilis, nucleoid occlusion has been reported to be mediated, at least in part, by the DNA-membrane bridging protein, Noc. Using time-lapse fluorescence microscopy of cells growing in microchannels, we show that Noc neither protects the chromosome from proximal Z-ring formation nor determines the future site of cell division. Rather, Noc plays a corralling role by preventing protofilaments from leaving a Z-ring undergoing cytokinesis and traveling over the nucleoid.

scholarly journals Cell growth dilutes the cell cycle inhibitor Rb to trigger cell division

2018 ◽  
Author(s):  
Evgeny Zatulovskiy ◽  
Daniel F. Berenson ◽  
Benjamin R. Topacio ◽  
Jan M. Skotheim
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Growth ◽  
Cell Size ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Inverse Correlation ◽  
Cell Types ◽  
Similar Amount ◽  
Cell Cycle Inhibitor

Cell size is fundamental to function in different cell types across the human body because it sets the scale of organelle structures, biosynthesis, and surface transport1,2. Tiny erythrocytes squeeze through capillaries to transport oxygen, while the million-fold larger oocyte divides without growth to form the ~100 cell pre-implantation embryo. Despite the vast size range across cell types, cells of a given type are typically uniform in size likely because cells are able to accurately couple cell growth to division3–6. While some genes whose disruption in mammalian cells affects cell size have been identified, the molecular mechanisms through which cell growth drives cell division have remained elusive7–12. Here, we show that cell growth acts to dilute the cell cycle inhibitor Rb to drive cell cycle progression from G1 to S phase in human cells. In contrast, other G1/S regulators remained at nearly constant concentration. Rb is a stable protein that is synthesized during S and G2 phases in an amount that is independent of cell size. Equal partitioning to daughter cells of chromatin bound Rb then ensures that all cells at birth inherit a similar amount of Rb protein. RB overexpression increased cell size in tissue culture and a mouse cancer model, while RB deletion decreased cell size and removed the inverse correlation between cell size at birth and the duration of G1 phase. Thus, Rb-dilution by cell growth in G1 provides a long-sought cell autonomous molecular mechanism for cell size homeostasis.

Overexpression of a truncated cyclin B gene arrests Dictyostelium cell division during mitosis

1994 ◽  
Vol 107 (11) ◽  
pp. 3105-3114 ◽  
Author(s):  
Q. Luo ◽  
C. Michaelis ◽  
G. Weeks
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Growth ◽  
Dictyostelium Discoideum ◽  
Single Copy ◽  
Cyclin B ◽  
Dictyostelium Cell ◽  
Maximum Accumulation ◽  
Sequence Identity ◽  
Cyclin Gene

A cyclin gene has been isolated from Dictyostelium discoideum and the available evidence indicates that the gene encodes a B type cyclin. The cyclin box region of the protein encoded by the gene, clb1, has the highest degree of sequence identity with the B-type cyclins of other species. Levels of cyclin B mRNA and protein oscillate during the cell cycle with maximum accumulation of mRNA occurring prior to cell division and maximum levels of protein occurring during cell division. Overexpression of a N-terminally truncated cyclin B protein lacking the destruction box inhibits cell growth by arresting cell division during mitosis. The gene is present as a single copy in the Dictyostelium genome and there is no evidence for any other highly related cyclin B genes.

Wachstumsparameter in normalen und durch Actinomycin verlängerten Zellzyklen von Tetrahymena / Growth Parameters in Normal and Actinomycin-induced prolonged Cell Cycles of Tetrahymena

1969 ◽  
Vol 24 (12) ◽  
pp. 1624-1629 ◽  
Author(s):  
Günter Cleffmann
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
Cell Division ◽  
Dna Replication ◽  
Cell Growth ◽  
Rna Synthesis ◽  
Growth Parameters ◽  
Average Duration ◽  
Cell Cycles ◽  
Growing Cell

Actinomycin in low concentration (0,2 μg/ml — 0,5 μg/ml) prolongs the average duration of the cell cycle of Tetrahymena considerably, but does not inhibit cell division completely. Some parameters of the growing cell have been tested in cell cycles extended in this way and compared to those of normally growing cells. The RNA synthesis of treated cells is reduced to such an extent that the RNA content per cell decreases during the prolonged cell cycle. Nevertheless cell growth, protein synthesis and DNA replication proceed at almost the same rate as in untreated cells. These findings indicate that the presence of actinomycin does not interfere with RNA fractions necessary for growth but reduce the synthesis of RNA fractions which are essential for cell division. Therefore a longer period is needed for their accumulation.

scholarly journals GROWTH INHIBITION OF MURINE TUMOR CELLS, IN VITRO, BY PUROMYCIN, [6N]O2'-DIBUTYRYL 3',5'-ADENOSINE MONOPHOSPHATE, OR ADENOSINE

1973 ◽  
Vol 57 (2) ◽  
pp. 397-405 ◽  
Author(s):  
D. B. Thomas ◽  
Gay Medley ◽  
C. A. Lingwood
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Growth ◽  
Growth Inhibition ◽  
Tumor Cells ◽  
Growth Arrest ◽  
Adenosine Monophosphate ◽  
Synchronous Cultures ◽  
Murine Tumor Cells

The cytostatic effects of puromycm, [6N]O2'-dibutyryl 3',5'-adenosine monophosphate, and adenosine on asynchronous and synchronous cultures of the murine mastocytoma, P815Y, have been studied. Cell growth was arrested after a minimum of one further division. A model is proposed for the inhibition of cell division in which the periods of inhibition and growth arrest are separated in time by one cell cycle.

scholarly journals Specific Inhibition of Elm1 Kinase Activity Reveals Functions Required for Early G1 Events

2003 ◽  
Vol 23 (17) ◽  
pp. 6327-6337 ◽  
Author(s):  
Aparna Sreenivasan ◽  
Anthony C. Bishop ◽  
Kevan M. Shokat ◽  
Douglas R. Kellogg
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Growth ◽  
Kinase Activity ◽  
Budding Yeast ◽  
Specific Inhibition ◽  
Bud Emergence ◽  
Wee1 Kinase ◽  
Yeast Homolog

ABSTRACT In budding yeast, the Elm1 kinase is required for coordination of cell growth and cell division at G2/M. Elm1 is also required for efficient cytokinesis and for regulation of Swe1, the budding yeast homolog of the Wee1 kinase. To further characterize Elm1 function, we engineered an ELM1 allele that can be rapidly and selectively inhibited in vivo. We found that inhibition of Elm1 kinase activity during G2 results in a phenotype similar to the phenotype caused by deletion of the ELM1 gene, as expected. However, inhibition of Elm1 kinase activity earlier in the cell cycle results in a prolonged G1 delay. The G1 requirement for Elm1 kinase activity occurs before bud emergence, polarization of the septins, and synthesis of G1 cyclins. Inhibition of Elm1 kinase activity during early G1 also causes defects in the organization of septins, and inhibition of Elm1 kinase activity in a strain lacking the redundant G1 cyclins CLN1 and CLN2 is lethal. These results demonstrate that the Elm1 kinase plays an important role in G1 events required for bud emergence and septin organization.

scholarly journals PP2ARts1 is a master regulator of pathways that control cell size

2014 ◽  
Vol 204 (3) ◽  
pp. 359-376 ◽  
Author(s):  
Jessica Zapata ◽  
Noah Dephoure ◽  
Tracy MacDonough ◽  
Yaxin Yu ◽  
Emily J. Parnell ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Cell Size ◽  
Control Cell ◽  
Size Control ◽  
Regulatory Subunit ◽  
Delay Cell ◽  
Cell Cycle Entry ◽  
G1 Cyclin

Cell size checkpoints ensure that passage through G1 and mitosis occurs only when sufficient growth has occurred. The mechanisms by which these checkpoints work are largely unknown. PP2A associated with the Rts1 regulatory subunit (PP2ARts1) is required for cell size control in budding yeast, but the relevant targets are unknown. In this paper, we used quantitative proteome-wide mass spectrometry to identify proteins controlled by PP2ARts1. This revealed that PP2ARts1 controls the two key checkpoint pathways thought to regulate the cell cycle in response to cell growth. To investigate the role of PP2ARts1 in these pathways, we focused on the Ace2 transcription factor, which is thought to delay cell cycle entry by repressing transcription of the G1 cyclin CLN3. Diverse experiments suggest that PP2ARts1 promotes cell cycle entry by inhibiting the repressor functions of Ace2. We hypothesize that control of Ace2 by PP2ARts1 plays a role in mechanisms that link G1 cyclin accumulation to cell growth.

scholarly journals Instructive simulation of the bacterial cell division cycle

Microbiology ◽  
2011 ◽  
Vol 157 (7) ◽  
pp. 1876-1885 ◽  
Author(s):  
Arieh Zaritsky ◽  
Ping Wang ◽  
Norbert O. E. Vischer
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Dna Replication ◽  
Cell Mass ◽  
Time Lapse ◽  
Replication Initiation ◽  
Bacterial Cells ◽  
Bacterial Cell Division ◽  
Cycle Simulation ◽  
New Ideas

The coupling between chromosome replication and cell division includes temporal and spatial elements. In bacteria, these have globally been resolved during the last 40 years, but their full details and action mechanisms are still under intensive study. The physiology of growth and the cell cycle are reviewed in the light of an established dogma that has formed a framework for development of new ideas, as exemplified here, using the Cell Cycle Simulation (CCSim) program. CCSim, described here in detail for the first time, employs four parameters related to time (replication, division and inter-division) and size (cell mass at replication initiation) that together are sufficient to describe bacterial cells under various conditions and states, which can be manipulated environmentally and genetically. Testing the predictions of CCSim by analysis of time-lapse micrographs of Escherichia coli during designed manipulations of the rate of DNA replication identified aspects of both coupling elements. Enhanced frequencies of cell division were observed following an interval of reduced DNA replication rate, consistent with the prediction of a minimum possible distance between successive replisomes (an eclipse). As a corollary, the notion that cell poles are not always inert was confirmed by observed placement of division planes at perpendicular planes in monstrous and cuboidal cells containing multiple, segregating nucleoids.

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