Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of human recombinant DNA interferon alpha type A on nuclear inositol lipids, diacylglycerol (DAG) and DNA metabolism has been investigated in Friend erythroleukemia cells. A transient enhancement of phosphatidylinositol (4,5) - bisphosphate (PIP2) phosphorylation together with an increase of diacylglycerol mass were observed in nuclei isolated from cells treated with interferon alpha for 90 min. At the same time, a marked reduction of DNA polymerase alpha activity was observed, suggesting a possible involvement of nuclear inositol fraction in the response of the cell nucleus to interferon treatment.
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PMID:Interferon transiently modulates intranuclear signalling system in erythroleukemia Friend cells. 165 86

The commitment process of a human megakaryoblastic cell line (MEG-O1) induced with phorbol ester, TPA, was investigated with special reference to glycoprotein (GP) IIb/IIIa expression, multinuclear formation, and DNA replication. TPA (10(-7) mol/L) completely inhibited cellular division in MEG-O1, but did not suppress de novo DNA synthesis. Two days' culture with 10(-7) mol/L TPA was sufficient for MEG-O1 cells to initiate an irreversible commitment process. These cells could not resume cell growth and expressed GP IIb/IIIa antigen; some of them showed multinuclear form and DNA polyploidy even after removal of TPA from the culture medium. DNA histogram analysis showed that, upon treatment with TPA, the percentage of cells whose DNA ploidy was more than 8N was 5 to 10 times higher than that of control cells. Precise analysis using cell size fractionation by centrifugal elutriation method showed that there was strong correlation between the percentage of multinuclear cells and DNA polyploidy in TPA-treated cells. The percentage and staining intensity of GP IIb/IIIa and other megakaryocytic phenotypes such as von Willebrand factor and PAS staining were highest in large multinuclear cell populations, suggesting that these cells are the most differentiated population in this system. In TPA-treated cells, the activity of DNA polymerase alpha, a marker for cell growth, remained at the same level as in control cells. Aphidicolin, a specific inhibitor of DNA polymerase alpha, completely inhibited the differentiation induction of MEG-O1 cells with TPA measured by either GP IIb/IIIa expression or multinuclear cell formation. Therefore, DNA replication appears to be involved in the process of phenotypic expression as well as endomitosis in megakaryocyte differentiation of MEG-O1 cells. Aphidicolin was also effective in inhibiting megakaryocytic differentiation of other leukemia cell lines such as human erythroleukemia (HEL) and K562 cell lines induced with TPA, suggesting the close interplay of DNA replication and phenotypic expression in megakaryopoiesis.
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PMID:Aphidicolin, an inhibitor of DNA replication, blocks the TPA-induced differentiation of a human megakaryoblastic cell line, MEG-O1. 174 84

Aphidicolin, a specific and reversible inhibitor of DNA polymerase alpha, was examined as a potential tool to evaluate the relationship between proliferative and differentiative events in Friend erythroleukemia cell (FELC) maturation. Since FELC can be induced to differentiate along the erythrocytic pathway with a variety of inducing agents, the effects of aphidicolin were tested on proliferating FELC and cells which were induced to differentiate with the potent inducer, hexamethylene bisacetamide (HMBA). Exposure of FELC to aphidicolin resulted in unbalanced growth within 24 h, as reflected by abnormally large cells, compared with untreated cells. In the presence of 10 or 50 microM aphidicolin, 75-90% of cells became differentiated (benzidine+ cells) within 48 h, although by 72 h cells treated with aphidicolin were non-viable as determined by trypan blue staining. A wider range of aphidicolin concentrations was tested in an effort to determine the optimal concentration of aphidicolin that maximally induced differentiation with minimal loss of cell viability. Continuous exposure of FELC from 24-96 h with doses of aphidicolin ranging from 0.5 to 50 microM was more effective for differentiation induction than was short-term exposure (1, 2, 4, 12 h) to the drug, although 1 h of exposure significantly (p less than 0.01) increased differentiation (28.1 +/- 7.8%) compared with untreated cells (2.7 +/- 1.0%). When cells were treated with HMBA (5 mM) and aphidicolin (1, 5, 10 microM), in combination, aphidicolin shifted the time of onset of differentiation from 72 to 48 h, but did not act synergistically or additively with HMBA; nor was the induction effect of aphidicolin changed by HMBA. In contrast, suboptimal doses of aphidicolin (0.5 microM) in combination with HMBA (2.5 mM) produced an additive effect on FELC differentiation. In addition, [3H]thymidine experiments demonstrated that aphidicolin reversibly blocked FELC in S phase and at G1-S interface of the cell cycle. These results indicate that aphidicolin can induce the differentiation of FELC, and that a complete round of replicative DNA synthesis is not required for differentiation to occur.
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PMID:Effect of aphidicolin on Friend erythroleukemia cell maturation. 310 67

Cultures of murine Friend erythroleukemia (FL) cells, which are chronically infected with leukemia virus, were inoculated with vaccinia virus. The yield of vaccinia virus was determined by assaying plaque-forming units in mouse L2 cells, and the yield of leukemia virus was determined by measuring reverse transcriptase (RNA-dependent DNA nucleotidyltransferase) activity released into the culture fluid. Although no facilitation of one virus by the other was detected, persistently infected cultures were established. Electron microscopic examination revealed the presence of vaccinia and leukemia viruses in the same cell. The permanent lines of cells persistently infected with vaccinia were designated FLvac. Their morphology, growth rate, cloning efficiency, and ability to respond to the induction of erythrodifferentiation by treatment with dimethyl sulfoxide were not appreciably altered as compared to the parental FL cells. However, the persistently infected cells showed a marked decrease in tumorigenicity when assayed in DBA/2 mice. The infectious virus produced by FLvac cells and by L2 cells were indistinguishable as judged by restriction endonuclease patterns of virion DNA, structural proteins, and the activities of two virion-associated DNases. The yield of infectious vaccinia virus from FLvac cells generally declined after about 60 serial passages. Although some cell lines no longer yield infectious virus, they are resistant to challenge with vaccinia at concentrations that are cytolytic for L2 cells. The mechanism responsible for the establishment of the persistent infection remains unclear because defective particles, interferon production, and temperature-sensitive mutants have not been detected.
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PMID:Persistent infection of Friend erythroleukemia cells with vaccinia virus. 695 93

Translation of ribosomal protein (rp) mRNA is selectively repressed in mouse erythroleukemia (MEL) cells, which cease to proliferate upon differentiation, and in NIH 3T3 cells, for which growth is arrested by either serum starvation, contact inhibition, or treatment with the DNA polymerase inhibitor, aphidicolin. The efficiency of translation of rp mRNAs correlates with the expression of the gene encoding the cap binding protein, eIF-4E, as indicated by the fact that the abundance of the corresponding mRNA and protein also fluctuates in a growth-dependent manner. To examine the hypothesis that eIF-4E plays a role in regulation of the translation efficiency of rp mRNAs, we utilized an NIH 3T3-derived eIF-4E-overexpressing cell line. These cells overproduce eIF-4E to the extent that even under conditions of growth arrest, the abundance of the respective protein in its active (phosphorylated) form is higher than that found in exponentially growing NIH 3T3 cells. Nevertheless, this surplus amount of eIF-4E does not prevent the translational repression of rp mRNAs when the growth of these cells is arrested by blocking DNA synthesis with aphidicolin or hydroxyurea. In complementary experiments we used an in vitro translation system to compare the competitive potential of mRNAs, containing the translational cis-regulatory element (5' terminal oligopyrimidne tract) and mRNAs lacking such a motif, for the cap binding protein. Our results demonstrate that both types of mRNAs, regardless of their translational response to growth arrest, exhibit similar sensitivity to the cap analogue m7G(5')ppp(5')G. It appears, therefore, that the presence of the regulatory sequence at the 5' terminus of rp mRNAs does not lessen its competitive potential for the cap binding protein and that the growth-dependent decrease in the activity of eIF-4E does not play a key role in the repression of translation of rp mRNAs.
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PMID:Overexpression of initiation factor eIF-4E does not relieve the translational repression of ribosomal protein mRNAs in quiescent cells. 778 16

The involvement of nuclear inositol lipids in the processes related to DNA repair upon ionizing radiation has been investigated in Murine Erythroleukaemia cells. Early changes in the in vitro phosphatidylinositol-bisphosphate phosphorylation in isolated nuclei were found to precede transiently the marked increase in DNA synthesis occurring after irradiation. Such an increase detected by anti-BrdU monoclonal antibodies has been found to be related mainly to DNA polymerase beta activity as revealed by the kinetic analysis of in vitro DNA synthesis. The results here presented allow us to speculate on a possible involvement of nuclear inositol lipids in the cascade of the early events leading to the regulation of DNA repair in the nucleus.
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PMID:Evidence for an early and transient involvement of nuclear inositol lipids in subcellular signalling events related to DNA repair processes. 794 71

We have studied the expression of genes encoding DNA replication proteins during different cell growth events. Gene expression of human DNA polymerase alpha-DNA primase, a principal chromosomal replication enzyme complex, is up-regulated during the entrance of a cell from quiescence into the mitotic cell cycle. In contrast, expression of these genes is greatly reduced in fibroblasts rendered temporarily quiescent by contact inhibition or serum starvation. In actively cycling cells, DNA polymerase alpha-DNA primase genes are expressed at all stages of the cell cycle. To investigate how their gene expression is regulated in cells permanently exiting the cell cycle during terminal differentiation, we used a novel method to obtain a pure population of such cells. In this report, we describe the down-regulation of gene expression of DNA polymerase alpha during both HL-60 (human myeloid) and MEL (mouse erythroleukemia) cell differentiation. Gene expression of the two subunits of DNA primase, p49 and p58, is also down-regulated at the mRNA level in differentiated MEL cells. In differentiated HL-60 cells, the decline of DNA polymerase alpha gene expression occurs at both the transcript and protein levels. Down-regulation of DNA polymerase alpha at the steady state transcript level is caused, at least in part, by a decreased rate of transcription initiation without transcription elongation block.
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PMID:Down-regulation of genes encoding DNA replication proteins during cell cycle exit. 804 55

We have examined the association of DNA polymerase alpha activity with the nuclear matrix prepared by different techniques from mouse erythroleukemia cells. At variance with the data obtained using other cell types we have found that only a small amount (less than 2%) of nuclear DNA polymerase alpha activity resisted extraction with high-ionic strength buffers, even if nuclei were heat-stabilized by incubation at 37 degrees C for 45 min prior to subfractionation. The recovery of DNA polymerase alpha activity bound to the matrix was unaffected by the type of extracting agent used (NaCl or (NH4)2 SO4), by the extraction sequence or by the method employed for obtaining nuclei. These results could indicate that in some types of cells the nuclear matrix is not involved in DNA replication.
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PMID:Absence of high levels of DNA polymerase alpha activity in the nuclear matrix prepared from mouse erythroleukemia cells. 837 95

During the latent period of murine erythroleukemia (MEL) cell differentiation, c-myc levels showed a significant change and the overexpression of the transferred c-myc gene inhibited the commitment and differentiation of MEL cells, suggesting that c-Myc may be a key molecule for the commitment. Since c-Myc may function as a DNA binding transcription factor, we examined whether c-Myc regulates the latent period genes (hsp and hsc70, MER5, Id and Spi-1 genes) and the erythroid-specific genes [beta-globin, glycophorin, delta-aminolevulinic acid synthase (ALAS-E), GATA-1 and erythropoietin receptor (EpoR)] in the MEL cell transformant having transferred c-myc gene. The overexpression of c-myc gene affected the latent period genes in different ways: hsc and hsp 70 genes and Id gene were positively regulated, while expression of MER5 gene was repressed. While c-myc is thought to be involved in DNA replication, its overexpression showed no effect on the expression of proliferating cell specific nuclear antigen or DNA polymerase a. The overexpression of c-myc repressed the expression of glycophorin, ALAS-E and beta-globin genes, of the five erythroid-specific genes, but had no effect on expression of GATA-1 or EpoR gene. These results suggest that c-Myc differentially regulates the expression of the latent period and erythroid-specific genes.
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PMID:c-Myc selectively regulates the latent period and erythroid-specific genes in murine erythroleukemia cell differentiation. 840 52

Murine erythroleukemia (MEL) cells were exposed to a high pressure of 80 MPa or aphidicolin (APH), DNA polymerase inhibitor. The effects of caffeine on cell cycle were examined using these cells. During the culture of 80 MPa-treated MEL cells at atmospheric pressure, the cells arrested in the G2 phase, and cyclin B and hyperphosphorylated p34(cdc2) were accumulated. Namely, maturation promoting factor (MPF) composed of p34(cdc2) and cyclin B was inactive. However, upon exposure to caffeine, these cells entered prematurely into mitosis by activating MPF. Caffeine-induced premature mitosis was suppressed by butyrolactone I and orthovanadate. On the other hand, APH-treated MEL cells, which were not exposed to 80 MPa, were not so sensitive to caffeine-induced premature mitosis despite cyclin B accumulation. In this case, dephosphorylation of p34(cdc2) was not induced by caffeine. Interestingly, caffeine-induced premature mitosis in the 80 MPa-treated cells was also suppressed by APH. These results suggest that the premature mitosis of 80 MPa-treated MEL cells by caffeine is induced by active MPF, and that APH-sensitive molecules such as DNA polymerase may also play an important role in the checkpoint that controls the transition from G2 to M phase.
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PMID:High pressure sensitizes murine erythroleukemia cells to caffeine-induced premature mitosis. 1101 83


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