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)

Before an oxic cell sensitizer such as beta-ara A (a DNA-dependent DNA polymerase inhibitor) can be used in cancer treatment, it is essential to know both the influence of this type of drug on certain critical normal tissues and the role of proliferation kinetics in the radiosensitizing capacity. The biological system chosen for this in vitro study was the human fibroblast cell line HF19. Cells were studied in plateau phase and in the exponential growth phase. Cells were incubated with beta-ara A for 7 hr (1 hr before and 6 hr after irradiation). beta-ara A was extremely toxic to growing cells (concentrations ranging from 200 to 1000 microM), but no detectable effect was found on plateau-phase cells (up to 4000 microM). However, for a given drug concentration, the radiosensitizing effect (Sensitizing Enhancement Ratio SER) was very similar for growing and plateau phase cells (SER measured with Ds ratio was about 1.7 for a concentration of 500 microM). The enhancement ratio depended on the radiation dose; it was relatively higher for low doses. This can be explained by a differential effect of the drug on the alpha and beta components of the survival curve. Only the alpha component was increased.
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PMID:The effect of the oxic cell sensitizer, beta-ara A on human fibroblasts in plateau and in exponential growth phases. 271 77

Replication of hepadnaviruses involves a viral DNA polymerase containing both a DNA-dependent and an RNA dependent activity. This polymerase is a potential target for chemotherapy against hepatitis B. We have used human hepatitis B virus DNA-dependent DNA polymerase from human serum and duck hepatitis B virus DNA-dependent DNA polymerase from duck serum as well as RNA-dependent DNA polymerase activity from duck hepatitis B-infected duck liver. Triphosphates of thymidine analogs have been synthesized and tested for their inhibitory activities against these enzymes with the intention both to explore differences between these enzymes and structural requirements for inhibitors. The results showed that with the inhibitors tested, hepatitis B virus DNA-dependent DNA polymerase was the most sensitive enzyme and the triphosphate of 5-propenyl-2'-deoxyuridine was the most active inhibitor. In addition, the 5'-triphosphate of 5-propenyl-arabinofuranosyluracil also inhibited the hepadnavirus DNA-dependent DNA polymerases, and was a competitive inhibitor with respect to 2'-deoxythymidine triphosphate as showed by kinetic studies with duck hepatitis B virus DNA-dependent DNA polymerase from serum. Pharmacokinetic analysis showed 5-propenyl-2'-deoxyuridine to be well absorbed orally, but rapidly cleared from plasma. The arabinofuranosyl analog was also well absorbed but cleared less rapidly. Hence, these results indicate the potential of 5-propenyl-2'-deoxyuridine and 5-propenyl-arabinofuransyluracil for chemotherapy of hepatitis B.
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PMID:Inhibition of human hepatitis B virus DNA polymerase and duck hepatitis B virus DNA polymerase by triphosphates of thymidine analogs and pharmacokinetic properties of the corresponding nucleosides. 314 22

For the specific purification of eukaryotic DNA-dependent DNA polymerase alpha, we prepared two novel affinity resins bearing 5-(E)-(4-aminostyryl) araUTP as a ligand. One of them was araUTP-Sepharose 4B which was coupled directly with the ligand and the other was araUTP-Affi-Gel 10 which was coupled with the ligand through a spacer. No DNA polymerase alpha-primase activity from cherry salmon (Oncorhynchus masou) testes was bound on the araUTP-Sepharose 4B in all cases examined. On the other hand, the araUTP-Affi-Gel 10 retains this enzyme activity when poly(dA) or poly(dA)-oligo(dT)12-18 is present. The retained enzyme activity was sharply eluted around 100-mM KCl concentrations as a single peak, and this fraction showed a specific activity of about 170,000 units/mg as alpha-polymerase activity. The highly purified DNA polymerase alpha-primase isolated using the araUTP-Affi-Gel 10 contained only three polypeptides, which showed Mr values of 120,000, 62,000, and 58,000, respectively, as judged using sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
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PMID:AraUTP-Affi-Gel 10: a novel affinity absorbent for the specific purification of DNA polymerase alpha-primase. 321 43

The DNA polymerase of the Prague strain of Rous sarcoma virus of subgroup C and of the Schmidt-Ruppin strain of subgroup A has been solubilized. DNA polymerase purified by sucrose gradient sedimentation and chromatography on DEAE-cellulose represented less than 2% of the soluble [(14)C]protein of the virus. The enzyme was separated from 90% of the viral glycoprotein; it is probably different from the viral group-specific antigen. The sedimentation coefficient (s(20, w)) of the soluble DNA polymerase was 8 S before, and 6 S after, incubation with pancreatic RNase. The molecular weight of the 8S DNA polymerase was estimated to be about 170,000, and that of the 6S DNA polymerase to be about 110,000. Purified DNA polymerase had a high activity with 60-70S viral RNA or salmon DNA as template, but it had a low activity with heat-dissociated 60-70S RNA, influenza virus RNA, or the RNA of tobacco mosaic virus as template. Neither the 8S nor the 6S DNA polymerase had endogenous template activity. The DNA-dependent and the RNA-dependent DNA polymerase activities of the Prague strain coincided in sucrose gradients, both in the 8S and the 6S form. It is concluded that the RNA-dependent and the DNA-dependent DNA polymerase activities of the avian tumor viruses are probably due to the same enzyme.
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PMID:Properties of a soluble DNA polymerase isolated from Rous sarcoma virus. 432 88

Labeled virions of Rous sarcoma virus (RSV) were disrupted with detergent and analyzed on equilibrium sucrose density gradients. A core fraction at a density of approximately 1.24 g/cc contained all of the (3)H-uridine label and about 30% of the (3)H-leucine label from the virions. Endogenous viral deoxyribonucleic acid (DNA) polymerase activity was only found in the same location. Additional ribonucleic acid (RNA)- and DNA-dependent DNA polymerase activities were found at the top of the gradients. RNA-dependent and DNA-dependent DNA polymerase activities were also found in RSV-converted chicken cells. Particles containing these activities were released from cells by detergent and were shown to contain viral RNA. These particles were analyzed on equilibrium sucrose density gradients and were found to have densities different from virion cores.
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PMID:Comparison of Rous sarcoma virus-specific deoxyribonucleic acid polymerases in virions of Rous sarcoma virus and in Rous sarcoma virus-infected chicken cells. 432 52

Inhibition of the ribonucleic acid (RNA)- and deoxyribonucleic acid (DNA)-dependent DNA polymerase activities of mammalian C-type viruses was obtained with sera from rats bearing murine leukemia virus-induced transplant tumors. Polymerase activities of nonmammalian (viper) C-type virus and murine mammary tumor virus were not inhibited by such sera nor by serum from a rat immunized with the DNA polymerase of feline leukemia virus purified by isoelectric focusing. The latter serum appeared to inhibit preferentially the DNA-dependent DNA polymerase activity of mammalian C-type viruses showing no inhibition of RNA-dependent DNA synthesis.
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PMID:Specific inhibition of mammalian ribonucleic acid C-type virus deoxyribonucleic acid polymerases by rat antisera. 433 48

Nitroakridin 3582 (NA) formed complexes with native deoxyribonucleic acid (DNA) and with transfer ribonucleic acid (tRNA) species from Escherichia coli. Spectrophotometric titrations of NA with these nucleic acids produced numerical results from which nonlinear adsorption isotherms were derived. These curves indicated the existence of more than one class of binding sites on the polymers to which NA was bound by more than one process. The stoichiometry of strong binding of NA to double helical DNA was in agreement with a conventional value (1 ligand molecule per 4.2 component nucleotides) for complete intercalation binding. NA inhibited the DNA-dependent DNA polymerase I and RNA polymerase reactions, the first strongly and the second appreciably. These inhibitions corresponded to the extents to which NA inhibits DNA and RNA biosyntheses in vivo. Evidently, NA interferes with the template function of DNA. The drug also inhibited the polymerization of phenylalanine in a cell-free E. coli ribosome-polyuridylic acid [poly (U)] system. The effect paralleled an inhibition of the poly (U)-directed binding of phenylalanyl tRNA to ribosomes. Ethidium bromide acted similarly. The antimalarial drug, chloroquine, stimulated polyphenylalanine synthesis, apparently as a result of stimulating the poly (U)-directed binding of phenylalanyl tRNA to ribosomes.
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PMID:Antibacterial nitroacridine, Nitroakridin 3582: binding to nucleic acids in vitro and effects on selected cell-free model systems of macromolecular biosynthesis. 494 80

An RNA-dependent DNA polymerase was isolated from purified virions of endogenous oncornaviruses released by the MOPC-315 murine myeloma cell line. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the purified enzyme was found to consist of two major polypeptides with molecular weights of about 28,000 and 26,500. The active enzyme had a molecular weight of approximately 56,000, as calculated from its sedimentation on glycerol density gradients, indicating that it is probably a dimer of the two subunit polypeptides. The isolated MOPC-315 virus polymerase exhibited all three activities known to be found in the DNA polymerase from oncornaviruses, namely, an RNA-dependent DNA polymerase, a DNA-dependent DNA polymerase, and an RNase H. The RNA-dependent polymerase activity showed a prounced preference for Mn2+ over Mg2+, whereas the DNA-dependent and RNase H reactions were catalyzed by these two cations to an almost equal extent. The purified polymerase was found to be immunologically related to the polymerase of Rauscher murine leukemia virus.
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PMID:RNA-dependent DNA polymerase of an endogenous type C virus of mice: purification and partial characterization. 615 78

The activities of RNA-dependent DNA polymerase and DNA-dependent DNA polymerase were measured in hippocampus of fast and slow learning Wistar rats. The RNA-dependent DNA polymerase activity in the hippocampus of fast learning rats exceeds two-fold that in the slow learning ones, while the rates of the DNA-dependent DNA polymerase activities are similar. A significant increase in RNA-dependent DNA polymerase only was found in the hippocampus of rats 20 min after training for the conditioned food response before the trace consolidation registered 40 min after the training session. The data obtained are consistent with the suggestion that reverse transcription plays an important role in memory consolidation.
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PMID:Probable role of reverse transcription in learning: correlation between hippocampal RNA-dependent DNA synthesis and learning ability in rats. 619 Dec 60

Single-stranded short-chain RNA fragments, obtained by mild degradation of purified Escherichia coli ribosomal RNA(s) with pancreatic RNase A, exhibit particular biologic activities in vitro and in vivo. In vitro, these RNA fragments are used by DNA-dependent DNA polymerase I as primers to initiate the replication of DNA(s) isolated from rabbit bone marrow and spleen; they are inactive with DNA isolated from several normal tissues and cancerous cells. Administered iv, RNA fragments restore a normal level of circulating leukocytes in rabbits with high doses of cyclophosphamide (CP). Granulocyte/lymphocyte balance, upset by daily CP administration, is also restored during the increase of both types of cells. No toxicity is observed, and numerous repeated doses of RNA fragments show no cumulative effect and do not lead to loss of leukopoietic stimulating activity. Tumor-bearing mice can be protected by RNA fragments against the toxic effect of CP without impeding the anticancer activity of this drug.
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PMID:Leukocyte recovery with short-chain RNA fragments in cyclophosphamide-treated rabbits. 619 62


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