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)

DNA polymerase from RNA tumor viruses ("reverse transcriptase") has been analyzed for activities which have been associated with other DNA polymerases. Homogeneous DNA polymerase from avian myeoblastosis virus catalyzes pyrophosphate exchange and pyrophosphorolysis. Pyrophosphate exchange is dependent on a template and is base-specific. With avian myeloblastosis virus DNA polymerase, ribonucleotide templates are more efficient for synthesis while deoxyribonucleotide templates are more effective for pyrophosphate exchange. Synthesis, pyrophosphate exchange, and pyrophosphorolysis were inhibited by the chelating agent 1,10-phenanthroline, suggesting that enzyme-bound zinc is required for each of these reactions. The pyrophosphate exchange reaction was also demonstrated with the DNA polymerase from a mutant of Rous sarcoma virus that possesses a temperature-sensitive DNA polymerase. The pyrophosphate exchange reaction with the mutant polymerase is temperature-sensitive which demonstrates that pyrophosphate exchange is indeed catalyzed by the viral DNA polymerase and that the same mutation effects both DNA polymerase and pyrophosphatase activity. Unlike Escherichia coli DNA polymerase I, the DNA polymerase from avian myeloblastosis virus fails to degrade polydeoxyribonucleotides or to convert deoxynucleoside triphosphates into monophosphates. This lack of hydrolytic activities in avian myeoblastosis DNA polymerase should facilitate kinetic studies on the mechanism of DNA synthesis by this enzyme.
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PMID:On the fidelity of DNA replication. Enzyme activities associated with DNA polymerases from RNA tumor viruses. 5 14

The alkoxybenzophenanthridine alkaloids (coralyne acetosulfate, fagaronine chloride, and nitidine chloride) have been reported to possess antileukemic activity in mice. These compounds were tested for inhibition of reverse transcriptase activity of an RNA tumor virus and DNA polymerase, RNA polymerase, and polyadenylic acid polymerase activities of NIH-Swiss mouse embryos. Reverse transcriptase and DNA polymerase activities were strongly inhibited by these antileukemic alkaloids, whereas RNA polymerase and polyadenylic acid polymerase activities were only moderately affected. Viral and cellular DNA polymerase activities were potently diminished by the alkaloids when poly[d(A-T)], poly(dA)-oligo(dT), and poly(rA)-oligo(dT) template primers were used in the reaction mixture; however, no inhibition of enzyme activity was obtained with poly(rC)-oligo(dG) as template primer. These results suggest that alkoxybenzophenanthridine alkaloids inhibit DNA polymerase activity by interaction with A:T base pairs of the template primer.
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PMID:Inhibition of mammalian and oncornavirus nucleic acid polymerase activities by alkoxybenzophenanthridine alkaloids. 5 19

Several human prostatic tissues have been examined for possible particles and associated DNA polymerizing activity generally associated with the C-type RNA tumor virus family. Partially purified tissue extracts, when centrifuged to equilibrium in sucrose gradients, yield fractions which contain actinomycin D resistant, endogenous DNA polymerase activity; this activity bands at a density of 1.15-1.18 gm/cm3. Further analysis of the endogenous products by sucrose gradient sedimentation suggested the presence of high molecular weight RNA:DNA hybrids generally felt to be indicative of a faithful copy of a lengthy stretch of viral specific RNA. However, most of the DNA products synthesized in these endogenous reactions sedimented in much lower molecular weight regions of these sucrose gradients. Clearly, the relative distributions of "high" and "low" molecular weight products could critically depend on the nuclease content of the subcellular fraction under study, and the prostate may be relatively enriched in nucleases. Further, oligo (dT) stimulated the endogenous DNA polymerase activity contained in these extracts, and omission of one of the DNA precursor nucleotides depressed it. Thus, it seems unlikely that terminal transferase activity, rather than genuine DNA polymerization, was being measured primarily. Because of the spectrum of molecular weight classes formed by these DNA:RNA hybrids, as well as their apparent presence in normal prostatic tissue, we find it difficult to ascribe their presence with certainty either to the presence of typical C-type RNA viruses or to the exclusive behavior of the neoplastic prostatic tissue. Thus, our studies lend support to the growing evidence for functions similar to those of C-type RNA viruses being relatively widespread in human tissues without the apparent necessity for a possible etiologic role in neoplastic production (Strand and August, 1974; Sherr et al., 1974). At the same time, our current studies emphasize the need for caution in drawing conclusions from results utilizing probes generally felt quite useful in scoring for presence of virus in lower animals at least in the human prostate.
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PMID:RNA tumor virus-like activities in human solid tissues: endogenous RNA:DNA polymerase activities in the prostate. 5 36

It has been demonstrated that malignant diseases of the gastrointestinal tract and lung in humans possess three characteristics invariably found in ribonucleic acid tumor viruses: the presence of a ribonucleic acid directed deoxyribonucleic acid polymerase, reverse transcriptase; a high molecular weight ribonucleic acid with a sedimentation coefficient of 70 Svedberg units, and particulate elements with densities of 1.16 to 1.18 grams per milliliter sucrose gradient. Twelve of 17 carcinomas of the colon, three of five carcinomas of the stomach, all three carcinomas of the rectum and seven of ten carcinomas of the lung displayed detectable evidence of these viral-like entities. None of the corresponding normal tissues had positive reactions.
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PMID:Biochemical evidences for ribonucleic acid viral-like characteristics in malignant diseases of gastrointestinal tract and lung in humans. 5 52

The properties of an RNA-dependent DNA polymerase (an RNA-dependent DNA nucleotidyltransferase), which occurs ubiquitously in the allantoic fluid of uninfected, leukosis-virus-free eggs, are described. It is shown that the enzyme can synthesize faithful transcripts from natural RNA (globin mRNA). By biochemical and immunological methods, the enzyme can be clearly distinguished from the reverse transcriptases of the known chicken RNA tumor viruses and therefore seems to be a member of a so far unknown class of chicken polymerases.
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PMID:An RNA-dependent DNA polymerase, different from the known viral reverse transcriptases, in the chicken system. 6 87

An RNA-directed DNA polymerase associated with transformation-defective (td) segregant of Rous sarcoma virus (RSV) has been characterized. The enzyme required both a monovalent and a divalent cation, a sulfhydryl reducing agent, and all four deoxyribonucleoside triphosphates for the expression of maximal activity. Sensitivity of the endogenous RNA-directed DNA polymerase activity to a low concentration of pancreatic RNase indicated that the enzyme utilized the td virus endogenous RNA as template. Maximal DNA synthesis was observed in a reaction mixture of pH 8 - 8.5 at 45 C with a manganese concentration of 1 mM. The enzyme of the td virus responded to exogenous template-primers in a manner characteristic of DNA polymerase of RNA tumor viruses, and the response became substantially greater when noncomplementary precursors were omitted from the reaction mixture. The endogenous reaction kinetics were examined. Three phases of DNA synthesis could be distinguished. Evidence was obtained showing that during the third and slowest phase of DNA synthesis the reaction mixture was not depleted of precursors and that the enzyme was fully active to initiate DNA synthesis with newly-added viral or synthetic RNA templates. Comparison of TMP and dAMP incorporation kinetics suggested that at the initial phase the enzyme preferentially copies A-rich region(s) of viral RNA. A comparison was also made between the endogenous reaction of the td virus and that of its parent sarcoma virus. The pH optimum, metal ion requirements, effect of sulfhydryl agents, response to exogenous template-primers, and kinetics of DNA synthesis, were all compared. No significant difference between the reaction of the td virus and its sarcomatogenous counterpart could be demonstrated.
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PMID:Endogenous DNA polymerase of a transformation-defective rous sarcoma virus: characterization and comparison with the enzyme of the non-defective parent. 6 91

Complexes of high-molecular-weight RNA and reverse transcriptase (RNA-dependent DNA nucleotidyltransferase) have been detected in 14(77.8%) of 18 spleen from patients with Hodgkin's disease and in all samples tested of peripheral leukocytes and spleens from leukemic patients. The enzyme and its template are localized in a particle having a density between 1.16 and 1.19 g/ml. These observations describe characteristic features of RNA tumor viruses.
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PMID:Simultaneous detection of reverse transcriptase and high molecular weight RNA in tissue of patients with Hodgkin's disease and patients with leukemia. 6 53

Rauscher leukemia virus RNA-directed DNA polymerase has been purified to near homogeneity (greater than 90% pure) using affinity chromatography on polycytidylate-agarose with over 85% recovery of input enzymatic activity. The purified enzyme has a molecular weight of approximately 70,000 and appears to consist of a single polypeptide chain. The enzyme is free of DNase, but has RNase H activity. Analysis of the requirements for optimal rates of DNA synthesis by this enzyme using synthetic and natural template-primers has revealed template-specific variations in such requirements. During these studies it was observed that DNA synthesis catalyzed by Rauscher leukemia virus DNA polymerase is inhibited by the addition of inorganic phosphate. An analysis of the mechanism of phosphate inhibition was carried out using the synthetic template-primer poly(A)-(dT)10. It appears that by some mechanism, possibly involving the substrate binding site of the enzyme, phosphate ions inhibit DNA synthesis with a more acute effect on the rate of chain growth than on that of initiation. The extension of these studies to DNA synthesis catalyzed by a variety of mammalian type C viral reverse transcriptases revealed that low levels ( less than or equal to 2 mM) of inorganic phosphate strongly inhibited DNA synthesis. The susceptibility to phosphate inhibition appears unique to mammalian type C viral enzymes since the type B viral enzyme, Escherichia coli DNA polymerase I, avian myeloblastosis virus and Mason Pfizer monkey tumor virus reverse transcriptase and cellular DNA polymerases alpha and gamma are not inhibited by inorganic phosphate. This phenomenon of phosphate inhibition of various DNA polymerases, therefore, provides a new basis for the differentiation of the sources and nature of these enzymes.
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PMID:Purification and properties of Rauscher leukemia virus DNA polymerase and selective inhibition of mammalian viral reverse transcriptase by inorganic phosphate. 6 68

These studies were designed to determine if RIDP was present in a particulate fraction of brains from patients with ALS and PD. Evidence that we have detected RIDP is as follows: (a) DNA polymerase activity persists in the presence of concentrations of actinomycin D and distamycin that inhibit most DNA-directed DNA synthesis (25); (b) the majority of endogenous DNA polymerase activity is sensitive to prior treatment with RNase; (c) the early reaction product is a 4-5 S DNA heteropolymer joined by hydrogen bonds to an RNA molecule; and (d) the purified [3H]DNA product anneals to RNA extracted from the enzyme-containing pellet more extensively than to normal brain RNA or poly(rA). The enzyme activity is in a cytoplasmic particle that can be sedimented at high speed and has the buoyant density of RNA tumor viruses (1.16-1.18 gm/ml). This particulate fraction is not disrupted by physical manipulation and maintains its characteristic density with repeated centrifugations. Treatment with the nonionic surfactant Sterox changes the buoyant density of the enzyme-containing particle to 1.24 gm/ml, the density of the onconavirus virion core. Synthesis of RNA-DNA hybrids by an endogenous reverse transcriptase reaction was found only in normal and diseased Chamorro brains. Examination of a limited number of normal and diseased brains from individuals who lived in the United States produced negative results (39). Definitive characterization of this polymerase activity and identification as a true viral polymerase will depend on purification of biochemically active quantities of this polymerase to determine its template specificities, its cation preference, the fidelity of its transcription product, as well as its antigenic relationship to animal virus and human leukemic RIDP. Of critical importance in these studies will be differentiation of this activity from normal brain DNA polymerase gamma and terminal deoxynucleotidyltransferase.
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PMID:RNA tumor viruses as causative agents of chronic neurological disease. 6 87

Equine infectious anemia (EIAV) is shown to have an associated RNA-instructed DNA polymerase similar in its cofactor requirements and reaction conditions to the RNA tumor virus DNA polymerases. Demonstrating this DNA polymerase activity requires a critical concentration of a nonionic detergent, all four deoxyribonucleoside triphosphates, and a divalent metal ion. The reaction is sensitive to RNase, and a substantial fraction of the FNA synthesized is complementary to viral RNA. The detection of a complex of tritium-labeled polymerase product DNA-template RNA, which sedimented at 60S to 70S, provided evidence that EIAV contains high-molecular-weight RNA. These results, obtained with both virus propagated in cell culture and virus from the serum of an experimentally infected horse, indicate that EIAV may properly be considered a member of the family Retroviridae. They may also be pertinent to the mechanism(s) of viral persistence and periodic recrudescence of disease in chronically infected horses.
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PMID:RNA-dependent DNA polymerase associated with equine infectious anemia virus. 6 19


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