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 interaction of pyridoxal, pyridoxal-5'-mono-, di- and triphosphate with certain enzymes of polynucleotide synthesis (DNA-dependent RNA polymerase, DNA-dependent DNA polymerase I and polynucleotide phosphorylase from Escherichia coli and terminal deoxyribonucleotide transferase from calf thymus) was studied. All compounds tested was found to be reversible and competitive inhibitors of these enzymes. The reduction of the enzyme-inhibitor complex with NaBH4 gives rise to the complete irreversible inhibition of the enzymes under study. The comparison of the inhibition constants for pyridoxal and its phosphorylated derivatives with those for mono-, di- and triphosphates of nucleosides was carried out for the enzymes. The results obtained suggest that the modified epsilon-amino-group of lysine residue should be localized at the catalytic site in the vicinity of the pyrophosphate binding area of an enzyme.
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PMID:[Interaction of oligophosphates of pyridoxal with certain enzymes of polynucleotide synthesis]. 38 98

In order to ascertain the identity of the DNA-dependent DNA polymerase responsible for the observed DNA synthesis in nuclei isolated from baby-hamster kidney (BHK-21/C13) cells a comparative study was carried out on the effects of some drugs, reported to influence DNA synthesis, on DNA synthesis catalysed by these nuclei and by partially purified DNA polymerase-alpha and -beta. In all cases DNA synthesis by isolated nuclei and polymerase-alpha was inhibited to similar extents by N-ethylmaleimide, p-hydroxymercuribenzoate, novobiocin, heparin and phosphonoacetic acid; polymerase-beta was much less affected by these compounds. Ethidium bromide inhibited all DNA synthesis to similar extents, although at low concentrations (about 2 microgram/ml) synthesis in isolated nuclei was stimulated. The results are discussed in relation to the proposal that DNA polymerase-alpha catalyses the covalent extension of Okazaki fragments that these nuclei carry out in vitro.
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PMID:Effect of drugs on deoxyribonucleic acid synthesis in isolated mammalian cell nuclei. Comparison with partially purified deoxyribonucleic acid polymerases. 45 71

Certain L1210-active bis(guanylhydrazones) have structural and biological properties in common with the DNA minor groove binding, antileukemic, bisquaternary ammonium heterocycles. Monitoring of the DNA binding of the bis(guanylhydrazones), by fluorimetric quantitation of drug displacement of DNA-bound ethidium, shows that, like the bisquaternary salts, these agents bind more strongly to poly[d(A-T)] than poly[d(G-C)]. The drug concentrations necessary to inhibit L1210 DNA-dependent DNA polymerase in vitro by 50% (IC50) are linearly related to measures of drug-DNA binding with no preference for a particular primary sequence of DNA being evident. Mammalian toxicity of the bis(guanylhydrazones) is effectively modeled by a regression equation containing binomial terms in Rm values, used as a measure of agent lipophilic-hydrophilic balance, and the logarithms of the IC50 values.
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PMID:Potential antitumor agents. 31. Quantitative structure-activity relationships for the antileukemic bis(guanylhydrazones). 51 70

Spermatogenic cells separated by velocity sedimentation were analysed by a micro-procedure for differentiation-associated changes in DNA synthetic capabilities. DNA-dependent DNA polymerase activity is maximal in premeiotic and meiotic cells, sequentially declines in progressively more differentiated spermiogenic cells to a minimum value in testicular spermatozoa which is 1/14 of the maximum. No further decrease of activity is observed during the subsequent process of sperm cell maturation and, at the end-differentiated state, the potential of sperm cells for DNA synthesis is demonstrated by the presence of substantial activities of thymidine and thymidylate kinases as well as DNA polymerase activity, as determined by in vitro assay, are polymerase. Although levels of DNA polymerase activity, as determined by in vitro assay, are negatively correlated with the state of differentiation, the findings support the hypothesis that, in this cell system, DNA synthetic enzymes may not be limiting factors in the control of DNA synthesis.
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PMID:DNA synthetic capabilities of differentiating sperm cells. 59 Jun 57

DNA-dependent DNA polymerase has been extracted from the soluble cytoplasmic fraction of regenerating rat liver and purified using phosphocellulose and DEAE-cellulose chromatography. Glycerol gradient analysis showed that the enzyme was predominantly DNA polymerase alpha, having a sedimentation coefficient of 10.5 S at low ionic strength and of 6--8 S at higher salt concentrations. The fidelity of purified enzyme was assessed using the co-polymer poly(dA-dT).poly(dA-dT) as a template for DNA synthesis. For both the aggregated (10.5 S) and disaggregated (6--8 S) forms, fidelities in the range of 1 wrong base in 100,000--150,000 complementary bases were obtained.
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PMID:Molecular size and fidelity of DNA polymerase alpha from the regenerating liver of the rat. 62 56

Terminal deoxynucleotidyltransferase is an enzyme which has been found to be associated with thymus cells, bone marrow cells, as well as leukocytes from patients with acute lymphoblastic leukemia and chronic myelocytic leukemia in blast crisis. We report here the purification of terminal deoxynucleotidyltransferase by an oligonucleotide affinity (oligo(dT)12-18 cellulose) column. By using a 35 to 70% (NH4)2SO4 cut, Sephacryl S200 column and an oligo(dT) cellulose column, terminal deoxynucleotidyltransferase has been purified from calf thymus cells to a specific activity of more than 8,500 units/mg of protein. The terminal deoxynucleotidyltransferase purified by this method contains no detectable DNA-dependent DNA polymerase or endonuclease activities. Furthermore, sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the enzyme appears to be homogeneous, with two polypeptides corresponding to the two subunits alpha (10,000) and beta (23,000) of terminal deoxynucleotidyltransferase. These data indicate that oligo(dT)12-18 cellulose can be used as a rapid and selective affinity column for the purification of terminal deoxynucleotidyltransferase.
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PMID:Purification of terminal deoxynucleotidyltransferase by oligonucleotide affinity chromatography. 64 3

Quasi-homogeneous fractions of male mouse germ cells at definite stages of meiosis and spermiogenesis were obtained by using a separation method based on sedimentation velocity in an albumin gradient. In the various cell types, the total DNA-dependent DNA polymerase activity was determined, and the major enzymatic forms were characterized. The DNA polymerase species present in premeiotic, meiotic and post-meiotic cells were analyzed by glycerol gradient sedimentation. Two types of DNA polymerase were identified in fractions enriched in spermatogonia and preleptotene spermatocytes. One showed a sedimentation coefficient of about 7.5 S and was sensitive to N-ethylmaleimide (NEM); the other exhibited a sedimentation coefficient between 3 and 4 S and was resistant to NEM. On the basis of their sedimentation coefficients, their sensitivity to NEM and their template specificities, these 2 enzymes were identified respectively as alpha and beta DNA polymerases as reported in mammals. The gradient analysis performed on fractions enriched in meiotic and post-meiotic cells revealed the presence of DNA polymerase beta only. A quantitative analysis showed that the activity of the DNA polymerase beta reaches a maximum at middle-late pachytene stage and then drops gradually during spermiogenesis. Although any conclusion as to the biological role of this high level of DNA polymerase activity in pachytene spermatocytes is premature, it is tempting to suggest that this enzyme is involved in meiotic recombination.
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PMID:DNA-dependent DNA polymerase species in male germ cells of the mouse. 69 53

A ribonuclease-sensitive DNA polymerase, which uses an endogenous template, is detectable in the 39,000 g supernatant of a rat thymus homogenate, and appears as a single peak of activity in the void volume after Sephadex G 150 or G 200 gel filtration chromatography. Native and "activated" DNA-dependent DNA polymerase activities coincide with the endogenous-templated polymerase activity. Treatment of the thymus extract with ribonuclease(s) prior to gel filtration chromatography yields two other peaks of activity in addition to the void volume peak. The appearance of the two lower molecular weight peaks of activity is accompanied by a concomitant decrease in the endogenous-templated activity. The effect of ribonuclease is specific and cannot be reproduced by a similar deoxyribonuclease treatment.
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PMID:DNA polymerase activity associated with endogenous template: release by ribonuclease treatment. 80 37

A total of 18 compounds consisting of 7 alphatic and 7 aromatic bis(guanylhydrazones), p-quinone-bis(guanylhydrazone), one monoguanylhydrazone, one diamidine and one diguanidine were studied spectrophotometrically to determine their ability to interact with native calf-thymus DNA and the possible correlation of binding with biological activity. In each case, the ability of a compound to bind to DNA correlate with its ability to inhibit the activity of DNA-dependent DNA polymerase (EC 2.7.7.7) extracted from mouse leukemia L1210 cells. For example, all the aromatic bis-guanylhydrazones and diamidine (hydroxystilbamidine), which were good inhibitors of the enzyme activity, showed a biphasic interaction with DNA. All the aliphatic compounds displayed no detectable interaction with DNA in the Tris buffer used, and were also poor inhibitors of the polymerase activity. Interaction of decamethylene diguanide (Synthalin with DNA could not be determined because the compound does not absorb light in the UV-VIS region. However, in similarity with other aliphatic compounds, this agent was a poor inhibitor of DNA polymerase reduction. The p-quinone-bis(guanyl-hydrazone) and p-phenylbenzaldehyde-monoguanylhydrazone showed only a monophasic interaction with DNA and caused an intermediate inhibition of the enzyme activity. When tested for possible anti-leukemic activity against i.p. L1210 leukemia in syngeneic DBA/2J mice, all the aromatic bis-guanylhydrazones as well as hydroxystilbamidine caused prolongation of survival of tumor-bearing mice. Among the aliphatic bisguanylhydrazones, all of which showed no binding to DNA and caused at the most only a very slight inhibition of DNA polymerase, only methylglyoxal-bis(guanylhydrazone) (CH3--G) had antileukemic activity. Synthalin also inhibited leukemia growth. Evidences presented indicate that the mechanisms of action of aliphatic and aromatic bisguanylhydrazones may be quite different. Furthermore, the ability to bind to DNA may be a useful criterion to predict the antileukemic activity of aromatic guanylhydrazones and possibly other aromatic-bis-cationic compounds, but not that of aliphatic congeners.
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PMID:Studies on the structure--activity relationship among aliphatic and aromatic bisguanylhydrazones and some related compounds. 83 65

A DNA-dependent DNA polymerase from rat liver mitochondria was partially purified and characterized. Mitochondrial DNA polymerase has been found to be quite different from other DNA-dependent DNA polymerases alpha and beta present in the rat liver in the following points: elution patterns in a DEAE-cellulose column chromatography, sedimentation coefficients determined by the glycerol gradient centrifugation in the presence of high salt, and sensitivities to N-ethylmaleimide, ethidium bromide and KCl.
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PMID:Mitochondrial DNA polymerase from rat liver. 85 77


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