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)

A DNA polymerase (DNA nucleotidyltransferase) has been partially purified from a neck mass of an American patient with Burkitt lymphoma and separated from the cellular DNA polymerases. The molecular weight of the enzyme was approximately 90,000. The enzyme differs from the cellular DNA polymerases, but resembles herpes-virus-induced DNA polymerase in its primer template preference, high monovalent cation requirement for activity, and sensitivity to phosphonoacetate. Enzyme activity was inhibited specifically by an antibody directed against herpes-simplex-virus-induced DNA polymerase but not by antibodies directed against DNA polymerase alpha of HeLa cells and DNA polymerase gamma of a normal human lymphoblast cell line, NC37. Although serum of the patient with Burkitt lymphoma contained high Epstein-Barr virus titer, addition of the serum to the assay mixture did not have any effect on the activity of Burkitt lymphoma DNA polymerase. Tissues from spleen and liver of the patient with Burkitt lymphoma did not contain the herpes-virus-induced DNA polymerase. Detection of the herpes virus polymerase in the Burkitt lymphoma tissue provides additional evidence for the association of Epstein-Barr virus with this malignancy.
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PMID:Isolation of a herpesvirus-specific DNA polymerase from tissues of an American patient with Burkitt lymphoma. 21 56

Specificity of TdT5 as a marker for ALL was evaluated by determining its activity in cells from normal control subjects and from 35 pediatric patients with ALL, AML, Hodgkin's disease and disseminated Burkitt's lymphoma. We evaluated the DNA polymerase activity, cell surface phenotypes (E rosettes, EAC rosettes, Smlg and la-like, HTLA and cALL antigens), and hematological and cytochemical characteristics in both the normal and patient groups. DNA polymerase alpha + beta and DNA polymerase gamma activity were indiscriminately high in all immature cells as found in ALL, AML, Burkitt's lymphoma and phytohemagglutinin-stimulated normal lymphocytes, when compared to mature leukocytes found in normal individuals or in patients whose cancer was in remission. High TdT activity was found in 24 of 26 T and non-T/non-B ALL patients in active phase as well as in two of three AML patients one of whom had Auer rods. Thus, TdT, although valuable for monitoring ALL patients, may have limitations in separating AML from ALL.
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PMID:High terminal deoxynucleotidyl transferase activity in pediatric patients with acute lymphocytic and acute myelocytic leukemias. 27 33

While both primary and chronic herpes simplex virus (HSV) in vitro infections of a Burkitt's lymphoma-derived cell line (Raji) were similarly characterized by the induction of IgG-Fe receptors in about 50% of cells, the persistent HSV infection of Raji cells was also accompanied by an induction of surface-bound IgM in approximately 80% of cells. This IgM induction was suppressed by treating the infected cells with interferon, but not with phosphonoacetic acid, an inhibitor of herpes virus DNA polymerase activity. The fact that only the cell population which had lost this IgM expression was superinfectable would suggest that this Ig may play a protective role (e.g. antibody activity?) against HSV.
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PMID:Interferon-sensitive expression of membrane-bound IgM on a human lymphoid B cell line persistently infected with herpes simplex virus. 31 9

Epstein-Barr virus (EBV) infection and Plasmodium falciparum malaria are two known cofactors in the aetiology of endemic Burkitt's lymphoma. To assess the relation between these factors, limiting dilution analysis was used to assess the number of EBV-carrying B cells in the circulation of Gambian children during and after acute malaria. Numbers of virus-carrying cells were five times higher in acute malaria patients and in UK patients with infectious mononucleosis than in convalescent malaria patients and in healthy control adults from the UK. Spontaneous outgrowth in limiting dilution cultures from acute malaria samples was inhibited by acyclovir, a viral DNA polymerase inhibitor. The mechanism of outgrowth, therefore, was virus release from the in-vivo infected cell, which led to infection and immortalisation of co-cultured normal B cells. The findings provide evidence that acute malaria is associated with an increase in the number of EBV-carrying B cells in the circulation. Because of this increase, there is a greater chance of a cytogenetic abnormality occurring in such a cell, with consequent evolution of Burkitt's lymphoma.
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PMID:Circulating Epstein-Barr virus-carrying B cells in acute malaria. 167 68

Substantial evidence has implicated Epstein-Barr virus (EBV) in the aetiology of two human neoplasms, nasopharyngeal carcinoma (NPC) and Burkitt's lymphoma. This is supported by the presence of high antibody titres to EBV early antigen and virus capsid antigen, as well as antibody to two viral-associated enzymes, DNase and DNA polymerase. Patients with NPC, particularly the undifferentiated form, are commonly found to have EBV DNA in the tumour. Ito and others have presented strong epidemiological evidence that phorbol esters are related to the unusual geographic distribution of NPC in southeastern regions of China. There appears to be a close link between the widespread EBV infection of the Asian population and the distinct regional distribution in China of plants that produce diterpene ester. Naturally occurring phorbol esters are produced by plants of the Euphorbiaceae and Thymelaeaceae, which are used as traditional herbal medicines. Although it has been established that EBV can infect epithelial cells isolated from NPC as well as certain normal epithelial cells, there has been no in vitro evidence that EBV induces neoplastic transformation in normal human epithelial cells with or without exposure to phorbol esters. We report here evidence that transformation of normal human epithelial cells results from exposure to infectious EBV and that transformation is dependent on the presence of phorbol esters.
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PMID:Phorbol ester and Epstein-Barr virus dependent transformation of normal primary human skin epithelial cells. 244 17

Epstein-Barr virus (EBV)-specified DNA polymerase was purified from P3HR-1 cells, a Burkitt lymphoma EBV producer cell line, treated with phorbol-12,13-dibutyrate (PDB) and n-butyrate. Its inhibition by aphidicolin, phosphonoformate (PFA) and 5'-GMP was examined. Aphidicolin could inhibit EBV DNA polymerase competitively with respect to dATP and dCTP and noncompetitively with respect to dGTP and dTTP; whereas 5'-GMP was a noncompetitive inhibitor with respect to all four dNTPs. Combinations of aphidicolin and PFA, or PFA and 5'-GMP, produced a mutually exclusive inhibition pattern of EBV DNA polymerase that suggested that the binding sites of these compounds on the enzyme molecule are kinetically overlapping.
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PMID:Interaction of Epstein-Barr virus DNA polymerase with aphidicolin, phosphonoformate and 5'-GMP. 285 12

Until recently, lineage fidelity was thought to be preserved in leukaemic cells, which by available tests showed surface markers and enzymatic patterns characteristic of an appropriate normal cell lineage and stage of differentiation. Our data indicate that this theory is too restrictive. If leukaemogenesis occurs in pluripotent progenitors in a relatively high percentage of cases, we would propose a model in which lymphoid and myeloid differentiation antigens are expressed simultaneously until the progenitor cell commits to a single lineage. Lineage commitment could involve external factors, e.g. growth factors (Sherr et al, 1985), that cause genes specific for the opposite lineage to be 'switched off'. The control of gene expression in mammalian cells and the specific chromosomal sites of genes coding for the various lineage-associated markers remain uncertain. However, recent studies indicate that most, if not all, leukaemic cells contain chromosomal abnormalities, many involving rearrangements of DNA (Williams et al, 1986). Since the control of eukaryotic gene expression is known to involve numerous sequence elements, some acting at a distance from the site of transcription (Dynan and Tjian, 1985), genetic perturbations within the cell (e.g. a reciprocal translocation) could be expected to deregulate certain genes, leading to their under- or overexpression analogous to activation of the c-myc oncogene by the 8;14 translocation in Burkitt's lymphoma. Thus, an almost infinite variety of cell lineage-related phenotypes could be expected from this mechanism alone, even if the transforming event did not involve a pluripotent stem cell. Also, we have hypothesized that enzymes such as TdT, a DNA polymerase that catalyses polymerization of deoxyribonucleotides without a DNA template, could serve as a modifier of DNA sequences, permitting otherwise inactive genes to be expressed (Stass and Mirro, 1985). It is interesting that most cases of childhood acute mixed-lineage leukaemia are TdT positive, even though this is not true for the chronic leukaemias of adults. It is now clear that unusual combinations of myeloid and lymphoid cell lineages are much more common in acute leukaemia than have been generally recognized or suspected. The traditional division of the acute leukaemias into ALL and AML may not be the most accurate way to represent this class of haematological malignancies. That mixed-lineage leukaemia may require alternative therapy is a clinically important observation and underscores the need for comprehensive testing of blast cells at diagnosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Lineage heterogeneity in acute leukaemia: acute mixed-lineage leukaemia and lineage switch. 353 42

The relationship between the intracellular levels of DNA polymerase alpha (DP-alpha), adenosine deaminase (ADA) and lactate dehydrogenase (LDH) and the degree of malignancy of human lymphomas was investigated. Twelve non-neoplastic lymph nodes and 88 malignant lymphomas were examined. For non-Hodgkin's lymphomas (NHL) the low or high grade of malignancy was established according to three classifications: the Rappaport, the Kiel and the Working Formulation for Clinical Usage, with the latter also recognizing an intermediate grade group. Non-neoplastic lymph nodes had significantly lower levels of all the three enzymes than those found in high-grade malignant NHL (the P value ranged from less than 0.02 to less than 0.001). Hodgkin's disease, a slowly evolving neoplasia, showed lower levels of DP-alpha (P less than 0.001) and ADA (P less than 0.001), but not of LDH, than high-grade NHL. Among NHL, whatever classification was used, the low-grade malignant lymphomas had significantly lower levels than the high-grade ones for all the three enzymes (P less than 0.005 or P less than 0.001). The intermediate-grade group of the Working Formulation differed from the high-grade group for DP-alpha (P less than 0.01) and ADA (P less than 0.02) but not for LDH. It differed from the low-grade group only for ADA (P less than 0.005). Lymphoblastic and Burkitt's lymphomas were the groups with the highest levels of the three enzymes. Among low-grade lymphomas very low values were found in the histological entities defined as DLWD in the Rappaport classification, CLL and lymphoplasmacytoid immunocytoma in the Kiel classification and small lymphocytic (group A) in the WF. The levels of all enzymes in these histotypes were always significantly different from the other low-grade histotypes, and from the intermediate-grade ones of the WF. In the Kiel classification polymorphous lymphoplasmacytoid lymphoma, recently recognized as a group with a quite aggressive clinical course, was characterized by high levels of all three enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relation between enzymatic activities and the degree of malignancy of human lymphomas. 404 77

We have determined the levels of cellular DNA polymerases and Epstein-Barr virus specific DNA polymerase in three Burkitt's lymphoma cell lines producing varying amounts of EBV, one of which was induced by 12-0-tetra-decanoylphorbol-13-acetate (TPA). There was a proportional increase in the level of EBV-DNA polymerase with an increase in the percent of virus-producing cells. However, there was a reciprocal relationship between the levels of EBV-DNA polymerase and DNA polymerase alpha i.e., in cell line containing the highest level of EBV-DNA polymerase, activity of DNA polymerase alpha, but not of DNA polymerase beta, was reduced to an insignificantly low level. TPA does not have any direct effect on activities of either EBV-DNA polymerase or DNA polymerase alpha. EBV-DNA polymerases isolated from cells grown with or without TPA are indistinguishable in their properties such as elution position on phosphocellulose column, molecular weight, mono and divalent cation requirements, pH optimum, and other requirements for optimum activity. Addition of crude extracts of cells grown in presence of TPA to the purified DNA polymerase alpha did not inhibit its activity indicating that the observed loss was not due to any specific inhibitor present in TPA treated cells. Raji, a nonproducer cell line, did not contain EBV-DNA polymerase. There was no induction of EBV-DNA polymerase when Raji cells were grown in presence of TPA. The phenomenon of reduction in the levels of DNA polymerase alpha in cells induced to produce EBV may represent a mechanism by which the host DNA replication is shut off following virus infection.
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PMID:Cellular and Epstein-Barr virus specific DNA polymerases in virus-producing Burkitt's lymphoma cell lines. 628 81

The incorporation of ATP on poly(A) primers catalyzed by poly(A) polymerase was investigated in normal and neoplastic lymphoid cells from animal and human sources. High levels of the enzyme were found in mouse thymus, in chicken bursa and thymus, as well as in neoplastic cells from patients affected by lymphoblastic and Burkitt's lymphomas. Low or very low quantities were found in peripheral blood lymphocytes, chronic lymphocytic leukemia cells, normal lymph nodes and solid lymphoid tissues of Hodgkin's disease. In general, the enzymatic content of neoplastic lymphoid cells reflected those of their normal counterpart. No effect of fasting or cortisone treatment on poly(A) polymerase in mouse spleen, thymus or liver was found. No particular relationships with B, T or non-T, non-B lineages were observed, but some relationship with DNA polymerase alpha was found. Therefore, it may be that poly(A) polymerase levels are related to the proliferative activity of the cellular populations.
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PMID:Poly(A) polymerase distribution in normal and malignant lymphoid cells. 632 15


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