Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.7 (DNA polymerase)
17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Terminal deoxynucleotidyl transferase (TDT) is an unusual DNA polymerase that does not use template information to synthesize new strands of DNA. It is normally found in high concentration in thymus (50 u/10(8) cells) and in low concentration in bone marrow (less than 5 u/10(8)). We report TDT measurements in the marrow and/or peripheral blood of 51 adult patients, 28 of whom had leukaemia. TDT is present in very high levels (greater than 50 u/10(8) cells) in leukaemic lymphoblasts and in low levels in leukaemic myeloblasts (less than 9 u/10(8) cells). Of two patients who developed lymphosarcoma-cell leukaemia following treatment of poorly differentiated lymphocytic lymphoma, one had high and one low levels of TDT in the leukaemic blast cells. Leukaemic cells from three of seven patients with chronic myeloid leukaemia in blast crisis had TDT levels within the range expected of acute lymphoblastic rather than acute myeloid leukaemia. High TDT in leukaemic cells probably marks them as derivatives of lymphoid progenitor, thymic or pluripotential stem cells. Quantitative assay of TDT may provide information useful in classifying haematological neoplasms.
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PMID:Terminal deoxynucleotidyl transferase measurements in the differential diagnosis of adult leukaemias. 6 84

Northern poke lymphosarcoma DNA polymerase was partially purified from particulate fractions banding at 1.15 to 1.16 g/ml from homogenates prepared from frozen necropsies of tumor-bearing pike. The enzyme behaves as a typical reverse transcriptase, in that it prefers ribotemplates to deoxytemplates. The isoelectric point (pl 5.5) is similar to that of avian myeloblastosis virus polymerase. The pike enzyme elutes from a phosphocellulose column at 0.22 M potassium phosphate, the same as avian myeloblastosis virus DNA polymerase. The enzyme activity is inhibited by pyran, a specific inhibitor of viral DNA polymerases. The most striking difference between the pike lymphoma polymerase and the other viral DNA polymerases tested is the low maximum temperature of 20 degrees, compared to 30 degrees for Rauscher leukemia virus polymerase and 38 degrees for avian myeloblastosis virus and Rous sarcoma virus.
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PMID:Presence of DNA polymerase in lymphosarcoma in northern pike (Esox lucius). 6 92

For attempt to detect an etiological agent, cultures from bovine lymphosarcoma cases (adult form (ALS), calf form (CLS), and thymic form (TLS) were maintained in vitro for over a 18 month period. In two cultures from ALS, bovine leukemia virus (BLV) antigen was constantly detected. On the other hand, BLV antigen remained negative in cultures from two CLS and one TLS cases up to 40 passages. The RNA dependent DNA polymerase activities in these cultures were also negative. Treatment of a culture from CLS (3178) originated from liver tumor with 5'-iodo-2'-deoxyuridine (IdU) and dexamethasone (DXM) resulted in production of an agent serologically and morphologically similar to BLV and in alteration of cell morphology. No virus was detected in culture from TLS after treatment with IdU and DXM.
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PMID:Induction of C-type virus in cell lines derived from calf form bovine lymphosarcoma. 8 38

Two lines of the 6C3HED (Gardner lymphosarcoma), 6C3HED-LeP and 6C3HED-ADL, were studied. The former is exquisitely sensitive to 9-beta-D-arabinofuranosyladenine (ara-A) and the latter is resistant. Cytological examinations and strain specificity tests indicated that they are both 6C3HED. DNA synthesis in the sensitive line was found to be more sensitive to ara-A in whole-cell incubations than it was in the resistant line. In cell-free extracts, the DNA synthesis of the sensitive line showed greater inhibition by 9-beta-D-arabinofuranosyladenine 5'-triphosphate. Lower ability to form 9-beta-D-arabinofuranosyladenine 5'-triphosphate or to allow access to the intracellular space was eliminated as an explanation for the resistance. Cells from an ara-A-resistant human leukemia were tested, and the DNA synthesis of the cells, in either whole cells or cell-free extract, was unaffected by ara-A or 9-beta-D-arabinofuranosyladenine 5'-triphosphate, respectively. This suggests that resistance has emerged by reason of change in the DNA polymerase(s) and that the finding may be important in the clinical use of ara-A.
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PMID:Resistance to 9-beta-D-arabinofuranosyladenine in murine tumor cells. 58 Sep 2

2-Aza-1,N6-etheno-adenosine triphosphate (aza-epsilonATP), a fluorescent analog of adenosine triphosphate, significantly inhibits polyadenylate [poly(A)] polymerase of bovine lymphosarcoma and calf thymus, with 50% inhibition at 200 muM (in the presence of an equal concentration of adenosine triphosphate). Calf thymus RNA polymerases II and III are inhibited 32 and 20%, respectively, by a 3.8-fold excess of aza-epsilonATP; DNA polymerase alpha is not inhibited. The inhibition of poly(A) polymerase by aza-epsilonATP appears to be competitive with adenosine triphosphate; incorporation of aza-epsilonATP is not observed. Polymers of 2-aza 1,N6-etheno-adenosine monophosphate are used as primers, but pootly. 1,N-Etheno-adenosine triphosphate and 9-beta-D-arabinofuranosyladenine triphosphate are poor inhibitors of poly(A) polymerase; adenosine diphosphate is ineffective. Deoxyadenosine triphosphate inhibits to the same extent as aza-epsilonATP, while other naturally occurring nucleotides inhibit poly(A) polymerase to varying degrees, with deoxynucleoside triphosphates more potent than ribonucleoside triphosphates. Inhibition of poly(A) polymerase by naturally occurring nucleoside triphosphates suggests that nucleotides may regulate the enzyme in vivo; inhibition by the fluorescent analog aza-epsilonATP suggests that this compound may be useful in elucidating poly(A) metabolism in both normal and neoplastic cells.
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PMID:Inhibition of mammalian polyadenylate polymerase by 2-aza-1,N6-etheno-adenosine triphosphate. 98 43

The response of different tumours to radiation varies. This variation has been attributed to, among others, varying DNA repair capabilities The response of three tumour lines, differing in their sensitivities to radiation, namely, murine fibrosarcoma, lymphosarcoma and ascites, was studied by following the activities of enzymes known to be involved in DNA repair. The activities of poly (ADP-ribose) polymerase (PARP), DNA polymerase b and DNA ligase in fibrosarcoma, lymphosarcoma and ascites recorded varying degrees of increase following gamma irradiation (2 Gy). The increase was more pronounced in fibrosarcoma, which recorded a maximum 2 h after irradiation for b polymerase, and at 4 h for ligase and PARP, thereafter declining to near normal levels after 24 h. In contrast, the activity of DNA Topoisomerase I declined, corresponding to an increase in the PARP activity. The maximum increase in the activity of beta polymerase, ligase and PARP from lymphosarcoma and ascites was observed 2 h after irradiation with a corresponding decrease in Topoisomerase I activity. Search for the target enzymes and proteins for modification by PARP in gamma -irradiated fibrosarcoma tumour cells revealed that nuclei, and not chromatin, were preferentially modified by PARP. Among the nuclear proteins, histones were found to be ribosylated. The enzyme topoisomerase was ribosylated by PARP in vitro, and this modification was found to inhibit topoisomerase activity. We speculate that a possible role of PARP is to coordinate the activities of other enzymes in DNA repair by selectively inhibiting certain enzymes by the ribosylation process.
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PMID:Response of DNA repair enzymes in murine fibrosarcoma, lymphosarcoma and ascites cells following gamma irradiation. 1464 26