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)

Human x mouse hybrid clones obtained by fusing transformed human (VA2) cells with embryonic mouse brain cells were tested for their ability to spontaneously express type C virus particles. It had been previously shown that these hybrid cells preferentially retained human chromosomes while mouse chromosomes were lost. The culture fluid from one cell line was found to contain type C particle markers in abundance, and typical budding C particles were observed in the cells by electron microscopy. In contrast, no particle markers were detected in the culture fluid from parental cells and several other hybrid cell lines. Subclones of the virus-positive cell line continued to lose mouse chromosomes and were found to vary more than 100-fold in their culture fluid DNA polymerase activity. The hybrid cell viruses, termed HMV1, banded in a sucrose gradient between 1.14 and 1.16 g/ml, possessed viral group-specific antigens, and exhibited B-tropic host range for replication in mouse embryo cells, but did not replicate in human cells when directly applied. The virus did not transform mouse cells but was able to rescue the defective murine sarcoma virus from sarcoma-positive, helper-virus-negative cells. Activity of the DNA polymerase associated with HMV1 was similar to the activity of Rauscher murine leukemia virus (MuLV) DNA polymerase in its preference for poly(rA) over poly(dA) as a template, use of endogenous template, detergent requirement, and inhibition by antiserum directed against MuLV.DNA polymerase. The results suggest that human x mouse hybrid cells segregating mouse chromosomes can spontaneously express endogenous type C viruses and that such hybrid cell lines may be used for the isolation of latent mammalian oncornaviruses and analysis of viral gene regulation.
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PMID:Oncornavirus expression in human x mouse hybrid cells segregating mouse chromosomes. 436 59

Fourteen streptovaricin derivatives were tested for inhibition of cellular nucleotide polymerases (deoxyribonucleic acid polymerases alpha, beta, and gamma, terminal deoxynucleotidyltransferase [TdT], and ribonucleic acid polymerase II), simian sarcoma virus deoxyribonucleic acid polymerase, and herpes simplex virus type 1-induced deoxyribonucleic acid polymerase (HSV-DP). Three compounds (strep-tovadienal C, prestreptovarone, and streptoval Fc) preferentially inhibited TdT and HSV-DP over the other enzymes. These compounds inhibited HSV-DP more potently than they inhibited TdT. Evidence indicated that the mode of inhibition of TdT and HSV-DP by streptovadienal C and prestreptovarone was by interaction with the enzymes and not with template-primer, initiator, substrates, or divalent cations required for enzyme activity. Furthermore, data suggested that these compounds bind with greater affinity to HSV-DP than to TdT. Streptovadienal C and prestreptovarone were examined for their effect on the replication of herpes simplex virus type 1 in African green monkey kidney (CV1) cells. These compounds produced 2- and 3-log drops in virus titer, respectively, at concentrations not significantly affecting cell viability. This correlated with evidence indicating a greater binding affinity of these compounds for HSV-DP over cellular nucleotide polymerases.
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PMID:Inhibition of cellular and virus-associated nucleotide polymerases by, and anti-herpes simplex virus activity of, streptovaricin derivatives. 611 56

2',3'-Dideoxythymidine triphosphate differentially inhibited replicative DNA synthesis in permeable mouse ascites sarcoma cells and unscheduled DNA synthesis in bleomycin-treated permeable cells or in isolated rat liver nuclei. The mode of inhibition of 2',3'-dideoxythymidine triphosphate was competitive with respect to deoxythymidine triphosphate. 2',3'-Dideoxythymidine triphosphate inhibited replicative DNA synthesis with a Ki of 8 microM, whereas unscheduled DNA synthesis was more sensitive, the Ki being 0.5 microM. Referring to the differential sensitivity of DNA polymerases alpha and beta to 2',3'-dideoxythymidine triphosphate and to other related information reported previously, the present results suggested that DNA polymerase alpha is playing a major role in replicative DNA synthesis, and DNA polymerase beta in unscheduled DNA synthesis.
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PMID:Effects of 2',3'-dideoxythymidine triphosphate on replicative DNA synthesis and unscheduled DNA synthesis in permeable mouse sarcoma cells. 615 34

Chicken myeloblasts transformed by avian myeloblastosis virus (AMV) in the absence of nondefective helper virus (termed nonproducer cells) were found to release a defective virus particle (DVP) that contains avian tumor viral gag proteins but lacks envelope glycoprotein and a DNA polymerase. Nonproducer cells contain a Pr76 gag precursor protein and also a protein that is indistinguishable from the Pr180 gag-pol protein of nondefective viruses. The RNA of the DVP is 7.5 kilobases (kb) long and is 0.7 kb shorter than the 8.2-kb RNAs of the helper viruses of AMV, MAV-1 and MAV-2. Comparisons based on RNA.cDNA hybridization and mapping of RNase T1-resistant oligonucleotides indicated that DVP RNA shares with MAV RNAs nearly isogenic 5'-terminal gag and pol-related sequences of 5.3 kb and a 3'-terminal c-region of 0.7 kb that is different from that found in other avian tumor viruses. Adjacent to the c-region, DVP RNA contains a contiguous specific sequence of 1.5 kb defined by 14 specific oligonucleotides. Except for two of these oligonucleotides that map at its 5' end, this sequence is unrelated to any sequences of nondefective avian tumor viruses of four different envelope subgroups as well as to the specific sequences of fibroblast-transforming avian acute leukemia and sarcoma viruses of four different RNA subgroups. The specific sequence of the DVP RNA is present in infectious stocks of AMV from this and other laboratories in an AMV-transformed myeloblast line from another laboratory, and it is about 70% related to nucleotide sequences of E26 virus, an independent isolate of an AMV-like virus. Preliminary experiments show DVP to be leukemogenic if fused into susceptible cells in the presence of helper virus. We conclude that DVP RNA is the leukemogenic component of infectious AMV and that its specific sequence, termed AMV, may carry genetic information for oncogenicity. Thus we have found here a transformation-specific RNA sequence, unrelated to helper virus, in a highly oncogenic virus that does not transform fibroblasts.
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PMID:Genetic structure of avian myeloblastosis virus, released from transformed myeloblasts as a defective virus particle. 615 39

The RNA-dependent DNA polymerase (the reverse transcriptase) was solubilized from three related strains of avian sarcoma virus (ASV B77, ASV tsLA334, and ASV QV2) as well as avian myeloblastosis virus (AMV) and a chicken endogenous virus (RAV-O), by a combination of non-ionic detergent treatment and CsCl step-gradient centrifugation, and was subsequently separated into individual enzyme forms by poly(C)-agarose column chromatography. The newly developed two-step method allowed us to purify the three molecular forms (alpha-, alpha beta- and beta-form) of highly active enzyme rapidly and quantitatively from all the five virus strains examined. The molar ratio of the three enzyme forms differed among the virus strains: For the three sarcoma viruses, the major species was the alpha beta-form enzyme, the putative holoenzyme, and the alpha- and beta-form enzymes were less than a few percent and 15-25%, respectively, while the alpha-form enzyme content was higher for the two leukosis viruses than for the three sarcoma viruses. Both the total DNA polymerase activity and the content of the two enzyme subunits in purified virions of the three sarcoma virus was in the following order: ASV tsLA334 greater than ASV B77 greater than ASV QV2, which paralleled the virus yield at a permissive temperature in roller bottle cultures of chick embryo fibroblasts. No alteration was found in the thermolability of DNA polymerases between tsLA334, which carries ts mutations affecting both virus growth and cell-transformation, and other viruses.
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PMID:Reverse transcriptase associated with avian sarcoma-leukosis viruses. I. Comparison of intra-virion content of multiple enzyme forms. 617 23

A RNA-directed DNA polymerase was partially purified from a human homologous, mixed mesodermal sarcoma by DEAE-cellulose chromatography after sucrose density centrifugation. The enzyme transcribed poly(rA) most effectively but also transcribed poly(rI), poly(dA) and poly(rG) and to a lesser extent, poly(rmC). It was unable to transcribe poly(rU). The product with poly(rA) as template contained large material (greater than 28S) in addition to some proper size product demonstrating a slippage reaction. This pattern of transcription, while similar to avian myeloblastosis virus DNA polymerase, reveals qualitative differences making direct extrapolation from studies with animal oncornaviruses to human cancer difficult. In this paper, the detection and purification of RNA-directed DNA polymerase from a patient with an uncommon uterine sarcoma is reported along with the template specificities of the enzyme.
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PMID:Template specificities of a RNA-directed DNA polymerase from a human homologous mixed mesodermal sarcoma. 619 Dec 64

The metabolism of pyrimidine nucleotides in various tissues and tumor cells of rodents was investigated. Ribonucleoside diphosphate reductase, thymidine monophosphate kinase and DNA polymerase (alpha, beta) were specifically localized in tumor cells, i.e., the activities of these enzymes in tumor cells were at least three times higher than those in normal tissues, including rapidly growing tissues, such as bone marrow, thymus, and spleen. The activities of deoxycytidine monophosphate deaminase and all the nucleoside kinase were high not only in tumor cells, but also in rapidly growing normal tissues, so that these enzymes are unsuitable as targets for cancer chemotherapy. The tissue distribution of other enzymes, including orotate phosphoribosyltransferases, cytidine triphosphate synthetase, thymidine monophosphate synthase, nucleoside phosphorylases and cytidine deaminase had no relation with the cell growth rate. AH130 tumor cells and the thymus showed specific increases in the activities of enzymes involved in de novo DNA synthesis. In contrast, Yoshida sarcoma and bone marrow showed high activities of enzymes in the salvage pathway of DNA synthesis, which suggested that the two tumors have different patterns of nucleotide metabolism.
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PMID:Metabolism of pyrimidine nucleotides in various tissues and tumor cells from rodents. 627 49

Short-term cultures of cells from human rain tumours have been reported to synthesise RNA particles of density in the range characteristic of C type RNA retroviruses, with associated DNA polymerase activity. Fresh tumour cells obtained from 6 children with astrocytoma and 7 children with medulloblastoma, together with one sample of normal brain tissue and normal leukocytes from brain tumour patients were assayed by several characteristics for the primate retrovirus. 1 or 6 (17%) astrocytomas and 4 of 7 (57%) medulloblastomas released RNA particles which banded in sucrose gradients at a density of 1.16-1.18 g/cm3 together with a short segment of DNA, which was eliminated by prior ribonuclease treatment and two proteins of 28k and 16k daltons. These findings were compatible with the presence of a primate retrovirus. Immune coprecipitation of 125I-labelled proteins from the 1.16-1.18 g/cm3 gradient region failed to show any reactivity with antisera to p28 core antigens or the p70 reverse transcriptase antigens of simian sarcoma virus, baboon endogenous virus or Mason Pfizer virus. Assays for DNA polymerase activity in culture supernatant fluid showed only a low amount of activity with template preferences not characteristic of the retroviral reverse transcriptase enzyme.
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PMID:Children's brain tumour cells produce RNA particles with incomplete retrovirus characteristics. 628 9

An unusual isozyme of lactate dehydrogenase, originally detected in Kirsten sarcoma virus-infected cells and later shown to be induced in normal mammalian cells by anaerobic shock, has also been reported at elevated levels in several human carcinomas. This enzyme is subject to inhibition by guanosine triphosphate and by the dinucleosides 5',5"'-diadenosine tetraphosphate and 5',5"'-diguanosine tetraphosphate (4). Fluctuation of the activity of this enzyme in soluble extracts of synchronized HeLa cells suggests the enzyme may be linked to DNA synthesis. The lactate dehydrogenase K activity increased in early S phase and then decreased to nearly undetectable levels during the period of most active DNA synthesis. This was observed in cells synchronized by thymidine excess or by aphidicolin, an inhibitor of DNA polymerase alpha.
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PMID:Fluctuation of a cancer-associated lactate dehydrogenase during S phase of the cell cycle in HeLa cells. 641 78

Aphidicolin clearly discriminated replicative DNA synthesis from unscheduled DNA synthesis. Aphidicolin inhibited replicative DNA synthesis in permeable mouse ascites sarcoma cells. The mode of inhibition of aphidicolin was a mixed type with respect to deoxycytidine triphosphate but was non-competitive with respect to the other three deoxynucleoside triphosphates. Aphidicolin did not affect the activity of unscheduled DNA synthesis in either bleomycin-treated permeable sarcoma cells or isolated rat liver nuclei. Considering the difference in sensitivity of DNA polymerase alpha and beta to aphidicolin, and other related information reported previously, the results are compatible with the idea that DNA polymerase alpha is involved in replicative DNA synthesis and DNA polymerase beta in unscheduled DNA synthesis in the present systems.
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PMID:Differential effects of aphidicolin on replicative DNA synthesis and unscheduled DNA synthesis in permeable mouse sarcoma cells. 678 76


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