scholarly journals Topoisomerase IIα Is Required for Embryonic Development and Liver Regeneration in Zebrafish

2009 ◽  
Vol 29 (13) ◽  
pp. 3746-3753 ◽  
Author(s):  
Michael Dovey ◽  
E. Elizabeth Patton ◽  
Teresa Bowman ◽  
Trista North ◽  
Wolfram Goessling ◽  
...  
Keyword(s):  
Positional Cloning ◽  
Topoisomerase Ii ◽  
Genetic Defect ◽  
Specific Marker ◽  
Adult Liver ◽  
Proliferating Cells ◽  
Topoisomerase Iiα ◽  
Lethal Mutant ◽  
A Cell ◽  
Heterozygous Phenotype

ABSTRACT Topoisomerases solve the topological problems encountered by DNA throughout the lifetime of a cell. Topoisomerase IIα, which is highly conserved among eukaryotes, untangles replicated chromosomes during mitosis and is absolutely required for cell viability. A homozygous lethal mutant, can4, was identified in a screen to identify genes important for cell proliferation in zebrafish by utilizing an antibody against a mitosis-specific marker, phospho-histone H3. Mutant embryos have a decrease in the number of proliferating cells and display increases in DNA content and apoptosis, as well as mitotic spindle defects. Positional cloning revealed that the genetic defect underlying these phenotypes was the result of a mutation in the zebrafish topoisomerase IIα (top2a) gene. top2a was found to be required for decatenation but not for condensation in embryonic mitoses. In addition to being required for development, top2a was found to be a haploinsufficient regulator of adult liver regrowth in zebrafish. Regeneration analysis of other adult tissues, including fins, revealed no heterozygous phenotype. Our results confirm a conserved role for TOP2A in vertebrates as well as a dose-sensitive requirement for top2a in adults.

scholarly journals Topoisomerase II: A specific marker for cell proliferation.

1986 ◽  
Vol 103 (6) ◽  
pp. 2569-2581 ◽  
Author(s):  
M M Heck ◽  
W C Earnshaw
Keyword(s):  
Dna Replication ◽  
Topoisomerase Ii ◽  
De Novo ◽  
Enzyme Level ◽  
Cell Types ◽  
Peripheral Blood Lymphocytes ◽  
Specific Marker ◽  
Proliferating Cells ◽  
Developmentally Regulated ◽  
Higher Eukaryotes

We have used an antibody probe to measure the levels of topoisomerase II in several transformed and developmentally regulated normal cell types. Transformed cells contain roughly 1 X 10(6) copies of the enzyme. During erythropoiesis in chicken embryos the enzyme level drops from 7.8 X 10(4) copies per erythroblast to less than 300 copies per erythrocyte concomitant with the cessation of mitosis in the blood. Cultured myoblasts also lose topoisomerase II upon fusion into nonproliferating myotubes. When peripheral blood lymphocytes (which lack detectable topoisomerase II) commence proliferation, they express topoisomerase II de novo. Appearance of the enzyme exactly parallels the onset of DNA replication. These results suggest that topoisomerase II is not required for transcription in higher eukaryotes, but that it may function during DNA replication. Furthermore, topoisomerase II is a sensitive and specific marker for proliferating cells.

scholarly journals Wnt Activity and Cell Proliferation Are Coupled to Extracellular Vesicle Release in Multiple Organoid Models

2021 ◽  
Vol 9 ◽  
Author(s):  
Gyöngyvér Orsolya Sándor ◽  
András Áron Soós ◽  
Péter Lörincz ◽  
Lívia Rojkó ◽  
Tünde Harkó ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Disease Diagnosis ◽  
Extracellular Vesicle ◽  
Cellular Heterogeneity ◽  
Ductal Adenocarcinoma ◽  
Diagnostic Tools ◽  
Proliferating Cells ◽  
Pathway Activation ◽  
A Cell ◽  
Potential Tool

Extracellular vesicles (EV) are considered as a potential tool for early disease diagnosis; however, factors modifying EV release remain partially unknown. By using patient-derived organoids that capture the cellular heterogeneity of epithelial tissues, here we studied the connection between the Wnt-producing microniche and EV secretion in multiple tissues. Although nearly all cells in pancreatic ductal (PD) and pancreatic ductal adenocarcinoma (PDAC) samples expressed porcupine (PORCN), an enzyme critical for Wnt secretion, only a subpopulation of lung bronchiolar (NL) and lung adenocarcinoma (LUAD) organoid cells produced active Wnt. The microniche for proliferating cells was shaped not only by PORCN + cells in NL and LUAD organoids but also by fibroblast-derived EVs. This effect could be blocked by using Wnt secretion inhibitors. Whereas inhibiting Wnt secretion in PD NL or LUAD organoids critically changed both cell proliferation and EV release, these were uncoupled from each other in PDAC. Sorting for CD133 identified a cell population in the LUAD microniche that produced organoids with a high percentage of PORCN + and proliferating cells and an elevated EV secretion, which may explain that CD133 marks LUAD cells with malignant behavior. Collectively, we show here that high cell proliferation rate, induced by Wnt pathway activation, is coupled to a higher EV release, a critical finding that may be considered when developing EV-based diagnostic tools.

scholarly journals Basic mechanism of eukaryotic chromosome segregation

2005 ◽  
Vol 360 (1455) ◽  
pp. 609-621 ◽  
Author(s):  
Mitsuhiro Yanagida
Keyword(s):  
Chromosome Segregation ◽  
Protein Modification ◽  
Topoisomerase Ii ◽  
Cell Cycle Control ◽  
Basic Feature ◽  
Basic Mechanism ◽  
Specific Protein ◽  
Eukaryotic Chromosome ◽  
Mitotic Cyclin ◽  
A Cell

We now have firm evidence that the basic mechanism of chromosome segregation is similar among diverse eukaryotes as the same genes are employed. Even in prokaryotes, the very basic feature of chromosome segregation has similarities to that of eukaryotes. Many aspects of chromosome segregation are closely related to a cell cycle control that includes stage-specific protein modification and proteolysis. Destruction of mitotic cyclin and securin leads to mitotic exit and separase activation, respectively. Key players in chromosome segregation are SMC-containing cohesin and condensin, DNA topoisomerase II, APC/C ubiquitin ligase, securin–separase complex, aurora passengers, and kinetochore microtubule destabilizers or regulators. In addition, the formation of mitotic kinetochore and spindle apparatus is absolutely essential. The roles of principal players in basic chromosome segregation are discussed: most players have interphase as well as mitotic functions. A view on how the centromere/kinetochore is formed is described.

scholarly journals Topoisomerase II alpha is associated with the mammalian centromere in a cell cycle- and species-specific manner and is required for proper centromere/kinetochore structure.

1996 ◽  
Vol 134 (5) ◽  
pp. 1097-1107 ◽  
Author(s):  
J B Rattner ◽  
M J Hendzel ◽  
C S Furbee ◽  
M T Muller ◽  
D P Bazett-Jones
Keyword(s):  
Cell Cycle ◽  
Topoisomerase Ii ◽  
Chromatin Condensation ◽  
Culture Cell ◽  
Centromeric Heterochromatin ◽  
Tissue Culture Cell ◽  
Topoisomerase Ii Alpha ◽  
A Cell ◽  
Topo Ii ◽  
Species Specific

A study of the distribution of Topoisomerase II alpha (Topo II) in cells of six tissue culture cell lines, human (HeLa), mouse (L929), rat, Indian muntjac, rat kangaroo (PTK-2), and wallaby revealed the following features: (1) There is a cell cycle association of a specific population of Topo II with the centromere. (2) The centromere is distinguished from the remainder of the chromosome by the intensity of its Topo II reactivity. (3) The first appearance of a detectable population of Topo II at the centromere varies between species but is correlated with the onset of centromeric heterochromatin condensation. (4) Detectable centromeric Topo II declines at the completion of cell division. (5) The distribution pattern of Topo II within the centromere is species- and stage-specific and is conserved only within the kinetochore domain. In addition, we report that the Topo II inhibitor ICRF-193 can prevent the normal accumulation of Topo II at the centromere. This results in the disruption of chromatin condensation sub-adjacent to the kinetochore as well as the perturbation of kinetochore structure. Taken together, our studies indicate that the distribution of Topo II at the centromere is unlike that reported for the remainder of the chromosome and is essential for proper formation of centromere/kinetochore structure.

scholarly journals Transfection of human topoisomerase IIα into etoposide-resistant cells: transient increase in sensitivity followed by down-regulation of the endogenous gene

1996 ◽  
Vol 319 (1) ◽  
pp. 307-313 ◽  
Author(s):  
Takeshi ASANO ◽  
Taeha AN ◽  
Janice MAYES ◽  
Leonard A. ZWELLING ◽  
Eugenie S. KLEINERMAN
Keyword(s):  
Topoisomerase Ii ◽  
Dexamethasone Treatment ◽  
Down Regulation ◽  
Topoisomerase Iiα ◽  
Endogenous Gene ◽  
Protein Levels ◽  
Mammalian Expression ◽  
Protein Complex Formation ◽  
Mmtv Promoter ◽  
Topo Ii

We have investigated the possibility of overcoming the resistance of human brain tumour cells (HBT20) to etoposide by transferring the normal human topoisomerase IIα (H-topo II) gene into these cells. H-topo II in a mammalian expression vector containing a glucocorticoid-inducible mouse mammary tumour virus (MMTV) promoter was transfected into etoposide-resistant HBT20 cells (HBT20-hTOP2MAM). HBT20 cells transfected with pMAMneo vector alone served as control cells (HBT20-MAM). These were stable transfections. Following a 2 h dexamethasone treatment, H-topo II mRNA expression, protein production, etoposide-induced DNA-protein complex formation and sensitivity to etoposide were increased in HBT20-hTOP2MAM cells compared with control HBT20-MAM cells and with HBT20-hTOP2MAM cells not treated with dexamethasone. However, mRNA and protein levels and cell sensitivity returned to baseline when incubation with dexamethasone was continued for 24 h. This decrease from the 2 h values could not be explained by a loss of the MMTV promoter response to dexamethasone. (H-topo IIα promoter)-(chloramphenicol acetyltransferase) constructs containing regions -559–0 and -2400–0 were significantly down-regulated in HBT20-hTOP2MAM cells treated for 24 h with dexamethasone compared with dexamethasone-treated control cells. H-topo II mRNA stability after 24 h of dexamethasone treatment was not altered compared with that in control cells. Our data indicate that the exogenously produced H-topo II may have a negative-feedback effect on the endogenous topoisomerase II promoter, causing down-regulation of the endogenous gene.

S-phase-specific expression of the Mad3 gene in proliferating and differentiating cells

2001 ◽  
Vol 359 (2) ◽  
pp. 361-367 ◽  
Author(s):  
Elizabeth J. FOX ◽  
Stephanie C. WRIGHT
Keyword(s):  
Cell Cycle ◽  
Cellular Proliferation ◽  
Cultured Cells ◽  
S Phase ◽  
Proliferating Cells ◽  
Specific Expression ◽  
Related Function ◽  
Erythroleukemia Cells ◽  
A Cell ◽  
Pass Through

The Myc/Max/Mad transcription factor network plays a central role in the control of cellular proliferation, differentiation and apoptosis. In order to elucidate the biological function of Mad3, we have analysed the precise temporal patterns of Mad3 mRNA expression during the cell cycle and differentiation in cultured cells. We show that Mad3 is induced at the G1/S transition in proliferating cells; expression persists throughout S-phase, and then declines as cells pass through G2 and mitosis. The expression pattern of Mad3 is coincident with that of Cdc2 throughout the cell cycle. In contrast, the expression of Mad3 during differentiation of cultured mouse erythroleukemia cells shows two transient peaks of induction. The first of these occurs at the onset of differentiation, and does not correlate with the S-phase of the cell cycle, whereas the second is coincident with the S-phase burst that precedes the terminal stages of differentiation. Our results therefore suggest that Mad3 serves a cell-cycle-related function in both proliferating and differentiating cells, and that it may also have a distinct role at various stages of differentiation.

scholarly journals Mass cytometry and artificial intelligence define CD169 as a specific marker of SARS-CoV2-induced acute respiratory distress syndrome

2020 ◽  
Author(s):  
M. Roussel ◽  
J. Ferrant ◽  
F. Reizine ◽  
S. Le Gallou ◽  
J. Dulong ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Specific Marker ◽  
Intelligence Analysis ◽  
Mass Cytometry ◽  
Hla Dr ◽  
A Cell

AbstractAcute respiratory distress syndrome (ARDS) is the main complication of COVID-19, requiring admission to Intensive Care Unit (ICU). Despite recent immune profiling of COVID-19 patients, to what extent COVID-19-associated ARDS specifically differs from other causes of ARDS remains unknown, To address this question, we built 3 cohorts of patients categorized in COVID-19negARDSpos, COVID-19posARDSpos, and COVID-19posARDSneg, and compared their immune landscape analyzed by high-dimensional mass cytometry on peripheral blood followed by artificial intelligence analysis. A cell signature associating S100A9/calprotectin-producing CD169pos monocytes, plasmablasts, and Th1 cells was specifically found in COVID-19posARDSpos, unlike COVID-19negARDSpos patients. Moreover, this signature was shared by COVID-19posARDSneg patients, suggesting severe COVID-19 patients, whatever they experienced or not ARDS, displayed similar immune dysfunctions. We also showed an increase in CD14posHLA-DRlow and CD14lowCD16pos monocytes correlated to the occurrence of adverse events during ICU stay. Our study demonstrates that COVID-19-associated ARDS display a specific immune profile, and might benefit from personalized therapy in addition to standard ARDS management.One Sentence SummaryCOVID-19-associated ARDS is biologically distinct from other causes of ARDS.

The murine dilute suppressor gene encodes a cell autonomous suppressor.

Genetics ◽  
1994 ◽  
Vol 138 (2) ◽  
pp. 491-497
Author(s):  
K J Moore ◽  
D A Swing ◽  
N G Copeland ◽  
N A Jenkins
Keyword(s):  
Positional Cloning ◽  
Genetic Basis ◽  
Coat Color ◽  
Suppressor Gene ◽  
Gene Products ◽  
Normal Melanocyte ◽  
Cell Processes ◽  
A Cell ◽  
Map Location ◽  
Coat Color Phenotype

Abstract The murine dilute suppressor gene (dsu) suppresses the coat-color phenotype of three pigment mutations, dilute (d), ashen (ash) and leaden (ln), that each produce adendritic melanocytes. Suppression is due to the ability of dsu to partially restore (ash and ln), or almost completely restore (d), normal melanocyte morphology. While the ash and ln gene products have yet to be identified, the d gene encodes a novel myosin heavy chain (myosin 12), which is speculated to be necessary for the elaboration, maintenance, and/or function of melanocyte cell processes. To begin to discriminate between different models of dsu action, we have produced aggregation chimeras between mice homozygous for dsu and mice homozygous for d to determine if dsu acts cell autonomously or cell nonautonomously. In addition, we have further refined the map location of dsu in order to examine a number of possible dsu candidate genes mapping in the region and to provide a genetic basis for the positional cloning of dsu.

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