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)

1-beta-D-Arabinofuranosylcytosine 5'-triphosphate (araCTP), an active form of a inhibitor of DNA replication, 1-beta-D-arabinofuranosylcytosine (araC) was tested for its inhibitory action on the DNA polymerase-alpha and -beta (EC 2.7.7.7) purified from calf thymus. The reaction of DNA polymerase-alpha was shown to be more sensitive to the inhibition by araCTP than that of DNA polymerase-beta. The mode of the inhibition by araCTP was competitive to dCTP in the reaction catalysed by either DNA polymerase-alpha or -beta. The Ki value of DNA polymerase-beta for araCTP was 32 micron; eight times higher than that of DNA polymerase-alpha (4 micron) for this inhibition.
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PMID:Inhibition of DNA polymerase-alpha and -beta of calf thymus by 1-beta-D-arabinofuranosylcytosine-5'-triphosphate. 32 50

The DNA polymerase in crude extracts of Drosophila melanogaster embryos sedimented at 9.0, 7.3, and 5.5 S on glycerol velocity gradients. The relative proportions of these enzymes depended on the method used to prepare the extract. Extracts of whole embryos contained the 7.3S and the 5.5S DNA polymerases and extracts of dechorionated embryos contained the 9.0S and 7.3S DNA polymerases. The porportion of the 5.5S DNA polymerase increased relative to the 7.3S DNA polymerase during storage of the extract of whole embryos. The protease inhibitor, phenylmethanesulfonyl fluoride, inhibited the formation of the 5.5S DNA polymerase, suggesting that it was proteolytically produced from the 7.3S DNA polymerase. This was demonstrated directly by converting the 7.3S DNA polymerase to the 5.5S DNA polymerase by treatment in vitro with trypsin. The degradation of the enzyme occurred without significant loss of DNA polymerase activity. It is further demonstrated that endogenous proteolysis reduced the chromatographic heterogeneity of the Drosophila DNA polymerase on diethylaminoethyl-Sephadex. When endogenous proteolysis was reduced, three forms of DNA polymerase were isolated by diethylaminoethylcellulose chromatography; two of these enzymes sedimented at 7.3S and the third sedimented at 9.0S. These results demonstrate the physical heterogeneity of the Drosophila DNA polymerase and suggest its similarity to vertebrate DNA polymerase-alpha.
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PMID:Multiple forms of Drosophila embryo DNA polymerase: evidence for proteolytic conversion. 40 23

The predominant DNA polymerase activity has been isolated from the parasitic flagellated protozoan, Trypanosoma brucei. Like mammalian DNA polymerase-alpha the trypanosome DNA polymerase is of large molecular weight (S, 6--8), is resistant to thermal denaturation, is sensitive to N-ethylmaleimide, and is inhibited by high ionic strength. However, specific antisera that cross-react with mammalian DNA polymerase-alpha from different species fail to cross-react with the trypanosome polymerase.
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PMID:Detection and characterization of DNA polymerase from Trypanosoma brucei. 42 Aug 46

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

Three forms of DNA polymerase (alpha, beta and gamma) were separated from isolated rat myocardial cells on the basis of template, pH and ionic requirements, sensitivity to N-ethylmaleimide and position on sucrose gradients. Tri-iodothyronine administration (20mug/100g intraperitoneally) to 3-week-old rats resulted in selective stimulation of DNA polymerase-alpha (198+/-7.1 versus 102+/-5.8pmol of [(3)H]dTMP/30min per mg of protein in untreated controls, P<0.01), with no change in polymerases-beta and -gamma. [(3)H]Thymidine incorporation into myocardial DNA was also enhanced in tri-iodothyronine-treated neonatal rats (132+/-11.2 versus 53+/-4.1c.p.m./mug of DNA in controls, P<0.001). Increased incorporation was associated with an expansion of deoxyribonucleoside 5'-triphosphate pools, especially that of dTTP (24+/-1.6 versus 10+/-1.1pmol/mg of DNA, P<0.01). Neither DNA polymerase activities nor [(3)H]thymidine incorporation were changed in 6-month-old rats in response to tri-iodothyronine. Unstimulated adult myocardial cells had DNA polymerase activities comparable with those in 3-week-old animals, but significantly lower [(3)H]-thymidine incorporation and deoxyribonucleoside triphosphate concentrations. Enhancement of both DNA polymerase-alpha activity and [(3)H]thymidine incorporation in tri-iodothyronine-treated young rats was prevented by concomitant administration of either vinblastine (1mug/g) or daunomycin (2mug/g); actinomycin D (0.1mug/g) or cycloheximide (8mug/g), on the other hand, prevented the increase in [(3)H]thymidine incorporation, but not DNA polymerase-alpha activation. These results demonstrate an age-dependent stimulation of myocardial DNA replication by tri-iodothyronine and suggest an inter-relationship between DNA synthesis and subsequent entry into mitosis.
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PMID:Selective stimulation by tri-iodothyronine of myocardial deoxyribonucleic acid polymerase-alpha in neonatal rats. 48 6

The kinetics of the inhibition of DNA polymerases-alpha and -beta from sea urchin embryos by pyridoxal 5-phosphate were studied. The inhibition of DNA polymerase-alpha activity by pyridoxal 5-phosphate was competitive with activated DNA but noncompetitive with each deoxynucleoside triphosphate. With poly(dC)-oligo(dG)12-18 as a template-primer, however, the inhibition of DNA polymerase-alpha was competitive with dGTP but noncompetitive with the template-primer. These results suggest that DNA polymerase-alpha interacts with activated DNA and poly(dC)-oligo(dG)12-18 in different ways. The inhibition of DNA polymerase-beta by pyridoxal 5-phosphate was competitive with deoxynucleoside triphosphate using activated DNA as a template-primer and noncompetitive with activated DNA. Using poly(rA)-oligo(dT)12-18 as a template-primer, DNA polymerase-beta activity yielded sigmoid curves against both dTTP and the template-primer concentrations and was inhibited by pyridoxal 5-phosphate noncompetitively with respect to both dTTP and the template-primer. These results indicate that the inhibitory mode of DNA polymerase-alpha by pyridoxal 5-phosphate is different from that of DNA polymerase-beta.
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PMID:The mode of inhibitory action by pyridoxal 5-phosphate on DNA polymerase-alpha and -beta. 50 44

An analysis of the accuracy of protein and DNA synthesis in human lymphocytes with respect to aging has been carried out. The response of human peripheral lymphocytes, from young and old adults, to phytohemagglutinin was measured at varying temperatures. This should provide a sensitive test for the accumulation of altered thermolabile proteins that are rate limiting in the response to phytohemagglutinin. At 37 degrees C the rate of thymidine incorporation as well as the induction of DNA polymerase in phytohemagglutinin-stimulated lymphocytes from old and young adults were similar. Also at elevated temperatures, the thermosensitivity of DNA replication in lymphocytes from young and old adults was the same. DNA polymerase was purified from PHA-stimulated lymphocytes from young and old adults. The fidelity of DNA synthesis using poly (dC) as a template was similar with both enzymes. However, DNA polymerase-alpha purified from old adults was thermolabile compared to the enzyme from young adults. Thus, while the lymphocytes from old individuals may have heat labile proteins, they do not limit their proliferative capacity.
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PMID:DNA replication in human lymphocytes during aging. 67 Mar 7

The activities of the three known DNA polymerases-alpha, beta-, and -gamma were determined in rat brain neurons, cardiac muscle and spleen, and were correlated with the rate of cell proliferation during perinatal development. In neurons and cardiac muscle, which stop dividing before birth, DNA polymerase-alpha activity drops sharply from a high level with the approach of term and disappears at approximately two weeks postnatal age. In contrast, alpha-polymerase activity is almost absent in spleen during late gestation, when the rate of cell division is low, and increases abruptly after birth with the sudden onset of cell proliferation. These data give further evidence for an involvement of DNA polymerase-alpha in DNA replication. DNA polymerase-beta and -gamma activities show essentially no correlation with the rate of cell division. Thus, these enzymes are probably responsible for repair type processes rather than for DNA replecation.
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PMID:Variation of DNA polymerases-alpha, -beta. and -gamma during perinatal tissue growth and differentiation. 90 96

We have developed a cytoenzymological method for localizing DNA polymerase activities in situ and for studying their responses to various chemical agents or environmental conditions. The incubation mixtures and the stimulatory or inhibitory agents added to these media were defined with reference to in vitro biochemical tests used to detect and to characterize DNA polymerases-alpha or -beta found in eukaryotic cells. This method has already been used to study DNA polymerase activities during cell differentiation or cell senescence. Apart from two exceptions found with lower organisms, the nuclear DNA polymerase activity was always higher under conditions which favoured the in vitro expression of DNA polymerase-beta rather than DNA polymerase-alpha. --In the various cell types studied, the cellular DNA polymerase activities were almost exclusively found in the nuclei. It is hoped that this methodology will be useful for obtaining more complete biochemical data on the intracellular localization of various DNA polymerases.
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PMID:In situ detection and characterization of DNA polymerase activities in the nucleus of eukaryotic cells. 92 89

Only one molecular weight species of DNA polymerase was found in different developmental stages of the eukaryotic microorganism Dictyostelium discoideum. The molecular weight of this DNA polymerase is estimated to be about 127 000 by sucrose gradient centrifugation. The enzyme is present in all stages of growth and development, including dormant spores. All DNA polymerase activity is lost upon incubation of the crude extract with N-ethylmaleimide. The reaction properties, molecular weight and N-ethylmaleimide sensitivity of the D. discoideum DNA polymerase are similar to those of the DNA polymerase-alpha from mammalian sources.
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PMID:DNA polymerase of Dictyostelium discoideum. 94 53


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