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)

Retrovirus particles with type C morphology were found in two T-cell lymphoblastoid cell lines, HUT 102 and CTCL-3, and in fresh peripheral blood lymphocytes obtained from a patient with a cutaneous T-cell lymphoma (mycosis fungoides). The cell lines continuously produce these viruses, which are collectively referred to as HTLV, strain CR(HTLV(CR)). Originally, the production of virus from HUT 102 cells required induction with 5-iodo-2'-deoxyuridine, but the cell line became a constitutive producer of virus at its 56th passage. Cell line CTCL-3 has been a constitutive producer of virus from its second passage in culture. Both mature and immature extracellular virus particles were seen in thin-section electron micrographs of fixed, pelleted cellular material; on occasion, typical type C budding virus particles were seen. No form of intracellular virus particle has been seen. Mature particles were 100-110 nm in diameter, consisted of an electron-dense core surrounded by an outer membrane separated by an electron-lucent region, banded at a density of 1.16 g/ml on a continuous 25-65% sucrose gradient, and contained 70S RNA and a DNA polymerase activity typical of viral reverse transcriptase (RT; RNA-dependent DNA nucleotidyltransferase). Under certain conditions of assay, HTLV(CR) RT showed cation preference for Mg(2+) over Mn(2+), distinct from the characteristics of cellular DNA polymerases purified from human lymphocytes and the RT from most type C viruses. Antibodies to cellular DNA polymerase gamma and anti-bodies against RT purified from several animal retroviruses failed to detectably interact with HTLV(CR) RT under conditions that were positive for the respective homologous DNA polymerase, demonstrating a lack of close relationship of HTLV(CR) RT to cellular DNA polymerases gamma or RT of these viruses. Six major proteins, with sizes of approximately 10,000, 13,000, 19,000, 24,000, 42,000, and 52,000 daltons, were apparent when doubly banded, disrupted HTLV(CR) particles were chromatographed on a NaDodSO(4)/polyacrylamide gel. The number of these particle-associated proteins is consistent with the expected proteins of a retrovirus, but the sizes of some are distinct from those of most known retroviruses of the primate subgroups.
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PMID:Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. 626 Dec 56

The incorporation of thymidine into the DNA of eukaryotic cells is markedly depressed, but not completely inhibited, by aphidicolin, a highly specific inhibitor of DNA polymerase alpha. An electron microscope autoradiographic analysis of the synthesis of nuclear and mitochondrial DNA in vivo in Concanavalin A stimulated rabbit spleen lymphocytes and in Hamster cell cultures, in the absence and in the presence of aphidicolin, revealed that aphidicolin inhibits the nuclear but not the mitochondrial DNA replication. We therefore conclude that DNA polymerase alpha performs the synchronous bidirectional replication of nuclear DNA and that DNA polymerase gamma, the only DNA polymerase present in the mitochondria, performs the "strand displacement" DNA synthesis of these organelles.
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PMID:An autoradiographic demonstration of nuclear DNA replication by DNA polymerase alpha and of mitochondrial DNA synthesis by DNA polymerase gamma. 626 34

Polyoma minichromosomes were isolated and fractionated on glycerol gradients as described by Gourlie et al. (J. Virol. 38:805-814, 1981). Specific assays for DNa polymerases alpha, beta, and gamma, DNA topoisomerase I, and RNase H were carried out on each fraction. The number of units of activity in each fraction was compared with the number of total polyoma and replicative intermediate DNA molecules in each fraction determined by quantitative electron microscopy (M. R. Krauss and R. M. Benbow, J. Virol. 38:815-825, 1981). DNA polymerase alpha cosedimented with polyoma replicative intermediate DNA molecules. DNA polymerase beta and DNA topoisomerase I activities sedimented with mature polyoma minichromosomes. Although the bulk of RNase H activity sedimented in the minichromosome region, the peak of activity was found one fraction behind the peak of mature minichromosomes. Virtually no DNA polymerase gamma activity cosedimented with polyoma minichromosomes.
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PMID:Polyoma virus minichromosomes: associated enzyme activities. 626 57

The content of DNA polymerase beta in whole rat testes drastically decreased upon hypophysectomy: at 1 and 2 weeks, to 12.5% and 5% of the control testes of sham-operated rats, respectively. DNA polymerase beta activity per cell (per milligram DNA) also decreased to 14% of the control within 2 weeks after hypophysectomy. The DNA polymerase alpha in the testis also decreased, but the DNA polymerase gamma was relatively resistant to hypophysectomy. The testicular DNA polymerase beta from hypophysectomized rats sedimented at 4.5 S, whereas that from sham-operated controls sedimented at 3.3 S. The reduced level of testicular DNA polymerase beta and the change in molecular size induced by hypophysectomy were largely reversed by daily injections of LH and FSH. The reduced activity was also fully reversed by the injection of testosterone. These results suggest that the level of DNA polymerase beta in the rat testis depends largely on the level of testosterone produced by Leydig cells in the testis itself, but is also regulated by pituitary gonadotropins.
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PMID:Hormonal regulation of deoxyribonucleic acid polymerase beta activity in rat testis. 643 Jun 81

We have studied the DNA polymerase activities in cultured cells and embryos of Med-fly (Ceratitis capitata Wied.) and we observed that only DNA polymerases alpha and gamma were detectable in crude extracts. The level of DNA polymerase alpha, measured during the life cycle of the insect embryos, increased in parallel with the rate of embryonic cell proliferation, whereas DNA polymerase gamma increased at much later fertilization time, when cell differentiation is already taking place. DNA polymerase alpha, purified 100 folds from Med-fly embryos, was 10 times more resistant to aphidicolin, its specific inhibitor, than the mammalian DNA polymerase alpha. In situ visualization of the active peptides after NaDodSO4/PAGE, confirmed that only high Mr DNA polymerase fragments were present in embryo extracts and in purified preparations of DNA polymerase alpha. It appears that C. capitata cells represent a rather peculiar system in the phylogeny of DNA polymerases since they are devoid of DNA polymerase beta and present a DNA polymerase alpha partially resistant to aphidicolin.
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PMID:A DNA polymerase alpha partially resistant to aphidicolin in cells and embryos of Med-fly (Ceratitis capitata Wied.). 643 30

The activities of DNA polymerases alpha, beta and gamma were determined in mouse liver as a function of age by a combination of glycerol density gradient centrifugation with polymerase specific assays. Although alpha polymerase was preserved throughout the life span, the activity dropped sharply from a high level at the fetal and neonatal stages to a level one order lower after maturation through adjustment of the amount of protein administered. beta polymerase showed similar but less drastic changes than alpha. DNA polymerase gamma activity increased about two-fold in going from newborn to adult stages and remained constant after maturation. According to the amount of DNA, DNA polymerase alpha decreased after birth, but the change was less drastic compared to that through adjustment of the amount of protein. DNA polymerase beta increased the activity 2-3-fold within a period of 3 months following birth. gamma polymerase underwent more than a 10-fold increase in activity through adjustment of the amount of DNA within the same period.
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PMID:Changes in DNA polymerases alpha, beta and gamma in mouse liver as a function of age. 665 15

DNA polymerase gamma, purified from fetal bovine liver, replicated virion single-stranded DNA from bovine parvovirus to a unit-length double-stranded DNA molecule. This product was not nicked and was covalently linked to the 3' hairpin primer. The reaction was inhibited by dideoxythymidine 5'-triphosphate, but was unaffected by ATP or aphidicolin. Double-stranded viral DNA was not a functional template for purified DNA polymerase gamma.
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PMID:Purified DNA polymerase gamma replicates bovine parvovirus DNA to a unit-length product. 666 Dec 43

Aphidicolin, a known inhibitor of DNA polymerase alpha, is a potent inhibitor of nuclear DNA synthesis in HeLa cells but has no effect on the replication of mitochondrial DNA. Parallel experiments with mitochondria incubated in vitro also show no inhibition of DNA synthesis by aphidicolin; however, DNA synthesis in these isolated mitochondria is completely blocked by dideoxycytidine triphosphate, which inhibits DNA polymerase gamma but not the alpha polymerase. The replication of mitochondrial DNA therefore requires only one DNA polymerase of the gamma type.
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PMID:Mitochondrial DNA replication does not involve DNA polymerase alpha. 677 85

There is strong evidence for a participation of DNA polymerase gamma in the replication of adenovirus (Ad) DNA. To study a possible additional role of DNA polymerase alpha we measured the effect of aphidicolin on viral DNA replication. In intact cells, aphidicolin inhibits Ad DNA synthesis weakly. The drug concentration required for 50% inhibition of Ad DNA replication was 300-400 fold higher than for a similar effect on cellular DNA synthesis. Such a differential inhibition was also observed in AGMK cells doubly infected with SV40 and the simian adenovirus SA7. No evidence was found for modification of aphidicolin in infected cells or for a change in aphidicolin sensitivity of DNA polymerase alpha after infection. The extent of inhibition of purified DNA polymerase alpha was dependent upon the dCTP concentration. The same situation was observed when DNA synthesis was studied in isolated nuclei from uninfected cells. However, in nuclei from Ad infected cells no effect of dCTP on aphidicolin sensitivity was found. These results were taken as evidence that DNA polymerase alpha does not participate in the replication of adenovirus DNA.
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PMID:Differential effect of aphidicolin on adenovirus DNA synthesis and cellular DNA synthesis. 677 59

DNA polymerase alpha, beta, gamma activities were determined after fractionation of loach (Misgurnus fossilis) cell extracts in glycerol gradients. The extracts of mature eggs, liver and testes cells yielded similar specific activities of DNA polymerase gamma (9-15 units/g protein) but differed markedly in the specific activities of DNA polymerases alpha and beta. A high activity of DNA polymerase alpha was revealed in the egg extract (2.0 X 10(3) units/g protein), while no DNA polymerase alpha activity was detected in liver cells. The specific beta-polymerase activity in the extract of mature eggs was extremely low (3.6 units/g protein), about two orders of magnitude lower than the enzyme activity in the extracts of liver or testes cells. The specific activity of DNA polymerases alpha and gamma changes insignificantly during oocyte maturation and embryogenesis up to the stage of hatching (50 h at 21.5 degrees C). As the mass of oocytes and embryos remains virtually unchanged at the stages studied, no substantial changes were observed in the alpha and gamma-polymerase activities per egg or embryo. The specific beta-polymerase activity in embryo cells increases about threefold by the completion of epiboly (20 h).
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PMID:Changes in DNA polymerase alpha, beta, gamma activities during early development of the teleost fish Misgurnus fossilis (loach). 688 67


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