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)

A number of reports have suggested that platelets from polycythemia vera patients contain reverse transcriptase activity that might be correlated with C-type retrovirus-like particles. As described herein, we devised a new assay method for reverse transcriptase activity using MS-2 phage RNA hybridized with synthetic oligodeoxynucleotide (18-mer) as a template/primer. Using this new, sensitive assay method, we examined the platelet enzyme. By the conventional assay method using poly(rA)-oligo(dT), extracts of platelets showed a considerable amount of incorporation. However, by the new assay method using MS-2 RNA, no incorporation was observed. The poly(rA)-oligo(dT)-dependent activity was purified on Mono Q column, and it was shown that this activity coincided with that of DNA polymerase gamma.
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PMID:Re-examination by improved reverse transcriptase assay of DNA polymerase in platelets from myelodysplastic disease patients. 248 74

Analysis of controlled studies performed by the Polycythemia Vera Study Group (P.V.S.G.) and the European Organization for Research in Treatment of Cancer (E.O.R.T.C.) indicate that busulphan (Myleran) (BU) is the treatment of choice for polycythemia vera (PV). BU is particularly effective as compared to aspirin and dipyridamole (Persantine) or radioactive phosphorus (32P) in preventing the thrombotic and atherosclerotic complications of PV. In contradistinction to chlorambucil (CM), BU is not associated with an unacceptable increase in the incidence of leukemia. The pharmacology of BU remains unclear, but certainly it cannot be considered a classic alkylating agent. BU suppresses the activity of the reverse transcriptase-like RNA dependent DNA polymerase in the platelets of these patients. A clearer understanding of the role of BU in the treatment of the myeloproliferative disorders will provide important insights into the etiology and pathogenesis not only of preneoplastic states, but also thrombosis and atherosclerosis.
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PMID:Busulphan: effect on platelet RNA dependent DNA polymerase--implications in the treatment of polycythemia vera, thrombosis and atherosclerosis. 618 58

Only 8% of the sequences of the genomes of pseudorabies (PRV) and herpes simplex (type 1) (HSV) viruses are homologous. These homologous sequences have been shown previously to be distributed throughout most of the genomes of the two viruses. By means of blot hybridization of restriction fragments of HSV-1 DNA to cloned, nick-translated restriction fragments of PRV DNA, it was possible to compare the location on the genomes of these viruses of the homologous regions. The results showed that the genome of PRV is, for the most part, colinear with the IL arrangement of the genome of HSV-1. An inversion or translocation of sequences mapping on the PRV genome between 0.07 and 0.39 map units was observed on the genome of one of these viruses. A comparison of the map positions of five genes with known functions confirmed these findings. The genes coding for the major immediate-early protein, the major capsid protein, and the thymidine kinase occupy similar positions on the genome of PRV and on the genome of HSV-1 in the IL arrangement. However, the genes for DNA polymerase and for the major DNA binding protein appear to be inverted relative to one another on the genomes of the two viruses.
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PMID:Localization of the regions of homology between the genomes of herpes simplex virus, type 1, and pseudorabies virus. 630 15

We have previously reported that particles resembling retroviral particles and possessing an RNA-directed DNA polymerase activity can be prepared from platelets. Furthermore, we and others have shown that these particles are present at higher levels in patients with essential thrombocythemia and polycythemia vera. We show here that these particles package RNA molecules that encode HERV-K-related pol genes. A subset of the RNA molecules that are packaged are likely to encode the RNA directed DNA polymerase activity and, because these RNAs possess long/full-length open reading frames for the reverse transcriptase and RNaseH (also for part of the integrase domains in genomic clones) of HERV-K, we propose that these transcripts are indeed strong candidates for encoding the enzyme activity found in these particles. Moreover, by using a modification of the polymerase chain reaction-based reverse transcriptase assay in which activated DNA is added during cDNA synthesis to suppress DNA polymerase-mediated RNA-directed DNA synthesis, we have found that the particle-associated enzyme behaves like a retroviral reverse transcriptase, further supporting the conclusion that retrovirus-like, perhaps HERV-K sequences, encode this enzyme activity.
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PMID:Evidence for copurification of HERV-K-related transcripts and a reverse transcriptase activity in human platelets from patients with essential thrombocythemia. 935 71

Substrate properties of the earlier synthesized and characterized dCTP derivatives bearing in the exo-N-position of cytosine 2-(4-azido-2,3,5,6-tetrafluorobenzoylamino)ethyl (I), 2-(2-nitro-5-azidobenzoylamino)ethyl (II), 2-(4-azido-2,3,5,6-tetrafluorobenzylideneaminooxymethylcarbonylamino)ethyl (III), 4-(4-azido-2,3,5,6-tetrafluorobenzylideneaminooxy)butyloxy (IV), or 4-(4-azido-2,3,5,6-tetrafluorobenzylidenehydrazinocarbonyl)butyl- carbonylamino (V) groups were studied in the primer extension reaction catalyzed by rat DNA polymerase beta. Unlike the earlier results obtained with HIV reverse transcriptase, dCTP derivatives (I)-(III) were not recognized by rat DNA polymerase beta as dTTP analogues, and all the five nucleotides were utilized as dCTP analogues. When compared with dCTP, Km values for the synthesized dCTP derivatives were higher by a factor of 4-20; Vmax were 1-2.3 times higher for (I)-(III) and (V) but 20-fold lower for derivative (IV). Site-specific photomodifications of the primer-template-DNA polymerase beta complexes were carried out using photoreactive reagents PRI-PRV, obtained in situ by extension of 5'-32P-labeled primers with dCTP analogues (I)-(V), respectively, when exposed to UV irradiation at 303-313 nm. Reagents PRI and PRIV provided the maximum photocrosslinking of the 5'-32P-labeled primer to the DNA template (56%) and to the enzyme (20%), respectively. The lowest efficiency of photocrosslinking was observed for PRII (about 1%).
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PMID:[Reagents for modification of protein-nucleic acids complexes. II. Site-specific photomodification of DNA-polymerase beta complexes with primers elongated by the dCTP exo-N-substituted arylazido derivatives]. 1144 42