Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Administration of ACTH to rapidly growing weanling rats results in an increase of DNA synthesis in adrenal and a decrease in liver. Dexamethasone administration decreases both adrenal and liver DNA synthesis. When both hormones were administered to the same animals, the liver DNA synthesis was similar to that observed with dexamethasone alone, but the DNA synthesis in adrenal was lower than that obtained with ACTH alone, yet higher than that observed with dexamethasone. The plasma levels of corticosterone were similar in animals treated with ACTH or with ACTH plus dexamethasone. Aminoglutethimide stimulated adrenal DNA synthesis, but less than ACTH. This substance overcame partially the inhibitory effects of dexamethasone on liver DNA synthesis but did not in adrenal. When both ACTH and aminoglutethimide were given simultaneously, adrenal DNA synthesis was higher than that observed with each substance alone. In all experiments in which adrenal cytosol DNA polymerase was studied, the activity varied in the same direction as DNA synthesis. These results indicate opposing effects of ACTH and glucocorticoids on adrenal DNA synthesis. The finding of a glucocorticoid effect on the adrenal is supported by the demonstration of a glucocorticoid specific binding protein in adrenal cytosol. Cycloheximide blocks the stimulatory action of ACTH on both steroidogenesis and DNA synthesis. Actinomycin D, as well as dexamethasone, blocks only the DNA synthesis-promoting action of ACTH. This latter result suggests some differences in the metabolic pathways by which ACTH controls steroidogenesis and growth in the adrenal cell.
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PMID:Opposite effects of ACTH and glucocorticoids on adrenal DNA synthesis in vivo. 19 Dec 38

Purified nuclei of HeLa S3 cells contain two DNA-dependent DNA polymerases that have distinct physical and enzymatic properties. We have investigated the variations in their activity during the cell cycle of a synchronized culture. Cells were synchronized by a double thymidine block, harvested at various phases of the cycle, and the two DNA polymerases were purified partially by DEAE-cellulose and phosphocellulose chromatography. The activity of DNA polymerase I (low molecular weight, N-ethylmaleimide-insensitive) remains essentially constant throughout the cycle. The activity of DNA polymerase II (high molecular weight, N-ethylmaleimide-sensitive), however, increases during G1 to mid-S and declines, 7- to 10-fold between late-S and G2. Addition of cycloheximide (60 mug/ml) to cultures 12 hours after the release from thymidine block abolishes the rise in the activity of DNA polymerase II. Cycloheximide also reduced the activity of DNA polymerase I by 60%. Addition of hydroxyurea (1mM) at 1 hour after release has no effect on the activity of either enzyme. We conclude that in HeLa cells, DNA polymerase I and II are distinct enzymes, that DNA polymerase II probably functions in DNA replication and is probably induced in response to stimuli for DNA biosynthesis.
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PMID:Nuclear DNA polymerases and the HeLa cell cycle. 24 Aug 45

Enzymes of deoxyribonucleotide and DNA biosynthesis, which are little known in plants, were studied in root tips of germinating broad beans (Vicia faba) and in fast-growing cultures of soybean cells (Glycine max). The plant cells contain a ribonucleoside 5'-diphosphate reductase which is detected in vitro only during a limited period of growth, viz. 30--32 h after inhibition of Vicia seeds, and between the second and third day after inoculation of soybean cultures. In both species ribonucleotide reductase activity precedes maximum DNA synthesis. The reductases could be precipitated with ammonium sulfate but were not purified further due to the extremely low enzyme content of the plant extracts. Therefore the reductive pathway of deoxyribotide formation was also established in Vicia root tips by efficient labeling of the plant DNA with a ribonucleoside, [5-3H]cytidine, which reaches a maximum at the same time as the reductase activity measured in vitro. Cycloheximide inhibits this process, indicating the need for de novo enzyme induction. In contrast, DNA polymerase is present in the tissue throughout the entire development and rises only 2-fold in activity during the S phase. The soluble polymerases were partially characterized in both legume species and were found very similar to the DNA polymerase of pea seedlings. Ribonucleotide reductase is more likely a limiting component of DNA formation during the plant cell cycle than DNA polymerase.
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PMID:Deoxyribonucleotide synthesis and DNA polymerase activity in plant cells (Vicia faba and Glycine max). 42 Aug 54

We have studied the expression pattern of the vaccinia virus DNA polymerase during the viral replicative cycle. To monitor polymerase synthesis, a polyclonal antiserum was raised against a TrpE-DNA polymerase fusion protein. Immunoprecipitation and S1 analyses revealed that polymerase synthesis and mRNA levels peak by 2 to 3.5 h postinfection during wild-type infections and then decline, becoming barely detectable by 5 to 6.5 h postinfection. Blocking viral DNA replication by performing infections with temperature-sensitive DNA- mutants at the nonpermissive temperature or by performing wild-type infections in the presence of cytosine beta-D-arabinofuranoside had no effect on polymerase expression. These results indicate that the transient expression of the DNA polymerase is regulated independently of intermediate and late viral gene expression. Cycloheximide, which inhibits protein synthesis and prevents secondary uncoating, caused prolonged and elevated levels of polymerase transcription. Early viral proteins and uncoating, rather than exhaustion of the encapsidated transcription machinery, are presumed to mediate the cessation of polymerase transcription. In the presence of aphidicolin, the polymerase transcripts were maintained at maximal levels rather than exhibiting their normal decline. This inhibition of RNA decay was seen even in infections performed with isolates encoding aphidicolin-resistant DNA polymerases, suggesting that aphidicolin may interfere directly with the process of RNA degradation. Under these conditions, polymerase synthesis remained transient and was not prolonged, despite the continuing presence of available mRNA. These observations suggest that early mRNAs may experience a loss in translation efficiency as infection progresses.
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PMID:Transient expression of the vaccinia virus DNA polymerase is an intrinsic feature of the early phase of infection and is unlinked to DNA replication and late gene expression. 172 98

A simultaneous increase is found in the level of protein synthesis and the major regulatory glycolytic enzyme, phosphofructokinase (PFK), in early phytohemagglutinin exposure of human lymphocytes. The induction of DNA synthesis is demonstrated to be a much later event. This indicates that the increase of glycolysis in mitogen-stimulated cells precedes cell proliferation, but occurs simultaneously with a general increase in protein synthesis. Chemical inhibitors are used to clarify the interrelationship of protein synthesis, glycolytic enzymes levels, and DNA synthesis. Inhibition of protein synthesis with cycloheximide in the mitogen-exposed lymphocytes prevents any increase in PFK levels, implicating protein synthesis as a cause for the increased glycolysis. Cycloheximide also prevents entry into S phase in mitogen-stimulated lymphocytes which may be due to inhibition of the synthesis of enzymes necessary for DNA synthesis, such as DNA polymerase. Aphidicolin, a specific DNA polymerase inhibitor, is found to have no effect on the increase in protein synthesis and PFK levels that precedes DNA synthesis. The increase in glycolysis in mitogen-stimulated lymphocytes occurs simultaneously with, and is dependent upon, increased protein synthesis, and precedes DNA synthesis and lymphocyte proliferation; thus, the high glycolytic rate of mitogen-stimulated cells is not merely a secondary manifestation of rapid cell proliferation as has been previously reported.
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PMID:The protein synthetic surge in response to mitogen triggers high glycolytic enzyme levels in human lymphocytes and occurs prior to DNA synthesis. 214 43

Cycloheximide strongly antagonizes the induction of sister-chromatid exchange by mitomycin C in Vicia faba root tips. This behavior is analogous to that previously observed in mammalian cells (Sono and Sakaguchi, 1981) and suggests that newly synthesized protein is also required for recombination between sister DNA molecules in plants. Conversely hydroxyurea is shown to increase the frequency of both spontaneous and induced sister-chromatid exchange. Based on these results, possible mechanisms underlying sister-chromatid exchange formation in plants are discussed with special emphasis on the absence of DNA polymerase beta in somatic tissues.
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PMID:The influence of a protein synthesis inhibitor on sister-chromatid exchange in the plant Vicia faba. 308 3

Inhibitors of DNA polymerase alpha (aphidicolin, phosphonoacetic acid, phosphonoformic acid) efficiently inhibit initiator-induced amplification of SV40 DNA sequences in the SV40-transformed Chinese hamster cell line CO631. Amplification is also inhibited by various protease inhibitors (antipain, leupeptin, aprotinin, alpha-I-antitrypsin, epsilon-amino-caproic acid, soy-bean protease inhibitor), by the non-initiating but DNA-damaging agent caffeine, and by sodium butyrate, which inhibits DNA synthesis by histone modification. In contrast, an inhibitor of topoisomerase II, nalidixic acid, enhances amplification when applied simultaneously with initiating treatment. This latter compound does not induce amplification when applied without initiator. Cycloheximide induces DNA amplification in the same way as chemical and physical carcinogens. This amplification can still be observed when protein synthesis is completely blocked. The data suggest a complex mechanism of selective DNA amplification. The possible involvement of proteases leading to a functional modification of DNA polymerase alpha is discussed.
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PMID:Selective DNA-amplification induced by carcinogens (initiators): evidence for a role of proteases and DNA polymerase alpha. 389 46

Cycloheximide reversal experiments in chick embryo fibroblasts and mouse L-929 cells indicate that the poxvirus-induced enzymes DNA polymerase and 'alkaline' DNase are immediate early gene products of the virus. In contrast to the vaccinia-WR-coded enzyme under conditions of immediate early gene expression the cowpox-virus-induced DNA polymerase is made only in very small amounts. The studies are consistent with the notion that all poxvirus-specific early proteins may be immediate early viral gene products.
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PMID:Synthesis of early vaccinia-virus-specific enzymes under conditions of immediate early gene expression. 647 64

Microinjection into bovine zygotes was performed to evaluate the effects of the timing of injection during the phase of DNA replication on the subsequent in vitro development of embryos and expression of injected chicken beta-actin promoter-lac Z gene construct. The period of DNA replication of bovine zygotes, determined by 3H-thymidine incorporation, begins between 12 hr and 13 hr postinsemination (hpi) of in vitro matured oocytes, reaches a maximum from 17 hpi to 19 hpi, and is complete by 21-22 hpi. Aphidicolin, an inhibitor of DNA polymerase alpha, was used to synchronize the pronuclei and the zygote population. Treatment with aphidicolin at 9-18 hpi arrested DNA replication without affecting formation of the pronuclei or embryo development. Cycloheximide, an inhibitor of protein synthesis, was used for nucleocytoplasmic resynchronization of the aphidicolin-treated zygotes. Microinjection was performed at 15 (early), 18 (mid), and 21 (late S phase) hpi. Embryonic development was affected following each of the three microinjection times. The development of zygotes injected at 18 hpi was significantly higher (P < 0.01) after 5 days of culture than those injected at 15 hpi or 21 hpi. Expression of the marker gene was observed in the higher stage of development (> 16 cells) only in the zygotes injected at 18 hpi. At the earlier stages of development, the proportions of embryos showing expression of the foreign gene were the same for all microinjection times. In aphidicolin- and cycloheximide-treated zygotes, expression of the marker gene followed the same curve as development, i.e., expression was low when injected early or late and higher (P < 0.005) when injected in the middle of zygotic S phase. The ability of the embryos to survive microinjection and to express the marker gene as a function of hpi seems to be influenced mostly in the cytoplasm processing stage rather than the pronuclei processing stage.
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PMID:Effect of microinjection time during postfertilization S-phase on bovine embryonic development. 765 72

The propensity of a cell to undergo apoptosis has been proposed to be a determinant for chemotherapy sensitivity that is not directly dependent on specific drug-target interactions. Androgen-independent prostate cancer is typically refractory to cytotoxic drugs, and we tested whether this is due to a loss of the ability to undergo apoptosis. Exposure of the hormone-insensitive and p53-negative human prostate carcinoma cell line PC-3 to 22 microM cisplatin, 1 microM camptothecin, 10 microM tenoposide, 135 nM vincristine, or 10 microM lovastatin for 72 h caused cell death, internucleosomal DNA fragmentation, and morphological changes typical for apoptosis. One microM cycloheximide prevented anticancer drug-induced apoptosis, whereas high concentration (1 mM) of cycloheximide alone induced apoptosis, indicating that protein synthesis was not needed for these cells to undergo apoptosis. Since cycloheximide affected DNA synthesis and proliferation of PC-3 cells, we tested whether the DNA polymerase inhibitor aphidicolin could also suppress drug-induced apoptosis. In contrast to cycloheximide, aphidicolin inhibited only vincristine-induced apoptosis. Cycloheximide prevented drug-induced changes in cell cycle distribution except for vincristine, while aphidicolin led to an accumulation of cells at the G1-S border independent of the drug used. These data indicate that macromolecular synthesis, active cell cycling, and p53 expression are not required for apoptosis to proceed in this system.
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PMID:Drug-induced apoptosis is not necessarily dependent on macromolecular synthesis or proliferation in the p53-negative human prostate cancer cell line PC-3. 774 12


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