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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)

DNA polymerase-alpha is the major replicative DNA polymerase in animal cells. The gene coding for a mutant DNA polymerase-alpha was transferred from one cell to another by transfection of DNA from mutant cells. The DNA was isolated from a mutant hamster cell line resistant to aphidicolin, a specific inhibitor of DNA polymerase-alpha, and transferred into an aphidicolin-sensitive cell line. The resulting transfectants exhibited increased survival in the presence of aphidicolin and contained an aphidicolin-resistant DNA polymerase-alpha.
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PMID:Transfection of the DNA polymerase-alpha gene. 643 77

In continuation of efforts to correlate the antitemplate activities of chemically modified polynucleotides with their base composition and structure, four synthetic copolymers, poly(A,C), poly(C,U), poly(A,C,U), and poly(A,C,G) were modified by thiolation of 2.6-4.8% of their pyrimidine bases. The resulting 5-mercaptoheteropolynucleotides and the previously described 5-mercapto-polycytidylate (MPC) and -polyuridylate (MPU) were tested in a comparative manner as inhibitors of the DNA polymerase-alpha from rat hepatoma. A wide scale of inhibitory potencies was obtained in the following (decreasing) order: MPU greater than M-poly(A,C,U) greater than M-poly(C,U) greater than MPC greater than M-poly(A,C) greater than or equal to M-poly(A,C,G). The sensitivity of the hepatoma DNA polymerase toward these antitemplates increased upon further purification of the enzyme through the DNA-agarose step. Partially thiolated DNA-isolates from rat hepatoma and calf thymus, respectively, showed significant inhibition of the hepatoma DNA polymerase, the thiolated hepatoma DNA being the more active inhibitor.
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PMID:Inhibition of DNA polymerase-alpha from rat hepatoma with a series of new synthetic polynucleotides. 661 28

Kinetics of cell replication was compared in regenerating livers of Mus musculus at ages ranging between 6 and 32 months. Incorporation of [3H]-thymidine into DNA and autoradiographic analysis showed that the maximal extent of DNA replication following partial hepatectomy became delayed with age. Furthermore, the total fraction of parenchymal and nonparenchymal cells in S phase at different intervals during regeneration diminished as mice aged. The specific activity of DNA polymerase-alpha, the putative replicative enzyme, declined progressively during aging. The specific activity of DNA polymerase-beta, the purported repair enzyme, declined to an appreciably lesser extent during the lifespan of the mouse. No evidence was found for the appearance of a specific inhibitor of polymerase-alpha in senescent mouse liver. Also, the bulk of the activities of both hepatic DNA polymerase-alpha and -beta remained localized in the cell nucleus throughout the lifetime of the animal and were mainly associated with chromatin.
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PMID:Delayed and reduced cell replication and diminishing levels of DNA polymerase-alpha in regenerating liver of aging mice. 669 97

3'-Amino-3'-deoxythymidine decreased the incorporation of [2-14C]thymidine into DNA of L1210 cells in vitro, and produced an accumulation of [2-14C]thymidine di- and triphosphate. The extent of these effects varied with the amount of recovery time after removal of 3'-amino-3'-deoxythymidine prior to addition of labeled thymidine. The distribution of radioactivity in the acid-soluble fraction derived from [3H]3'-amino-3'-deoxythymidine was as follows: 50% as 3'-amino-3'-deoxythymidine, 20% as the monophosphate, 10% as the diphosphate, and 20% as the triphosphate derivatives. No incorporation of [3H]3'-amino-3'-deoxythymidine into L1210 DNA could be detected. 3'-Amino-3'-deoxythymidine-5'-triphosphate is a competitive inhibitor against dTTP with a Ki of 3.3 microM, whereas the Km for dTTP was 8 microM using activated calf thymus DNA as the template and DNA polymerase-alpha. These data indicate that a major site of inhibition by 3'-amino-3'-deoxythymidine is inhibition of the DNA polymerase reaction.
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PMID:Molecular basis of the antineoplastic activity of 3'-amino-3'-deoxythymidine. 672 65

In the extract of mature sperm of the sea urchin, Hemicentrotus pulcherrimus, two species of DNA polymerase (deoxynucleosidetriphosphate:DNA deoxynucleotidyltransferase, EC 2.7.7.7.) activity were detected. One of them was eluted from a hydroxyapatite column at 0.08 M phosphate buffer and was insensitive to both N-ethylmaleimide and aphidicolin. The sedimentation coefficient was 3.3 S and the isoelectric point was pH 8.6. This activity corresponds to the DNA polymerase-beta activity. The other was eluted from the hydroxyapatite column at 0.14 M phosphate buffer and was inhibited by N-ethylmaleimide but not by aphidicolin. The sedimentation coefficient was 3.3 S and 6.0 S and the isoelectric point was pH 4.8. The template primer preference of this enzyme was coincident with DNA polymerase-gamma. The DNA polymerase-alpha activity was not detected in the extract of mature sperm.
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PMID:Characterization of DNA polymerases in mature sperm of the sea urchin. 677 24

Antibodies to homogeneous calf thymus DNA polymerase-beta and calf thymus DNA polymerase-alpha preparations were raised in rabbits. The antiserum against calf thymus DNA polymerase-beta cross-reacts with all vertebrate DNA polymerase-beta preparations tested, but does not cross-react with trypanosome DNA polymerase-beta, DNA polymerase-gamma, terminal transferase, yeast DNA polymerases, and Escherichia coli DNA polymerase I. The antibodies against calf thymus DNA polymerase-alpha cross-react with DNA polymerase-alpha from mouse, human, and chicken, but do not cross-react with DNA polymerase-alpha from sea urchin embryos and Drosophila embryos, DNA polymerase-beta, DNA polymerase-gamma, terminal transferase, yeast DNA polymerases, and E. coli DNA polymerase I.
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PMID:Immunological reagents for comparisons of DNA polymerase-alpha and DNA polymerase-beta. 677 65

Four distinctive DNA polymerases have been isolated from mature oocytes of the starfish, Asterina pectinifera, and characterized. The N-ethylmaleimide-resistant DNA polymerase activity was separated from the other three DNA polymerases by hydroxyapatite column chromatography. The enzyme, whose approximate sedimentation coefficient was 3.3S, effectively utilized poly(dA)-oligo(dT) as a template-primer and was completely inhibited by 10 microM 2', 3'-dideoxythymidine-5'-triphosphate but was not inhibited by aphidicolin. Therefore, this enzyme was classified as a eukaryotic DNA polymerase-beta. Three species of the N-ethylmaleimide-sensitive DNA polymerase were separated with a phosphocellulose column. Two (5.5S and 6.5S) of the enzymes eluted from the column preferred activated DNA as a template-primer. Both of the DNA polymerases were inhibited by aphidicolin but not by 2',3'-dideoxythymidine-5'-triphosphate. Judging from the above results, these two DNA polymerases were classified as eukaryotic DNA polymerase-alpha. The third N-ethylmaleimide-sensitive enzyme (approximately 7S) eluted from the phosphocellulose column utilized poly(rA)-oligo(dT) as well as poly(dA)-oligo(dT) as template-primers. The enzyme activity was resistant to aphidicolin but sensitive to 2',3'-dideoxythymidine-5'-triphosphate. This enzyme resembles eukaryotic DNA polymerase-gamma. Thus, it is concluded that the four species of DNA polymerase found in starfish oocytes resemble eukaryotic DNA polymerase-alpha, -beta, and -gamma.
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PMID:Isolation and characterization of DNA polymerases from mature oocytes of the starfish, Asterina pectinifera. 687 60

A DNA polymerase activity has been identified in the plasma membranes isolated from a rat hepatoma (the Zajdela Ascitic Hepatoma). The enzyme activity was found specifically associated with the detergent insoluble skeleton of the plasma membranes from which it cannot be dissociated by conventional methods. The properties of the enzyme are indistinguishable from those of DNA polymerase-alpha.
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PMID:A DNA polymerase activity associated with the skeletal framework of the plasma membranes of a rat hepatoma. 688 43

In the present study, effects of various 2- and 2'-substituted polyadenylic acid analogs on eukaryotic, bacterial and viral DNA polymerases were investigated. The polymer containing 2'-deoxy-2'fluoroadenosine, (dAfl)n, showed a concentration dependent stimulation of (rA)n . (dT)12-catalyzed reverse transcriptase reaction from Rauscher Leukemia Virus (RLV). A similar stimulation of the (rA)n . (dT)12-catalyzed DNA polymerase-gamma reaction was also observed. However, the (rC)n . (dG)12-dependent reverse transcriptase activity was inhibited by (dAfl). The DNA polymerase-beta activity catalyzed by (dA)n . (dT)12 was also inhibited by (dAfl)n. The reported data indicate that (dAfl)n closely resembles (rA)n as a functional template. In contrast, the 2-substituted derivatives, poly(2-methylthioadenylic acid) and poly(2-ethylthioadenylic acid), are not able to discriminate between the reactions catalyzed by different templates. For example, both derivatives inhibit (rA)n . (dT)12- and (rC)n . (dG)12-catalyzed reverse transcriptase reaction to the same extent; though the methylthio derivative is a much better inhibitor than the ethylthio analog. The DNA polymerase-alpha was less sensitive to these inhibitors; whereas the bacterial DNA polymerase (Kornberg enzyme; DNA polymerase I) was completely resistant to the action of all the derivatives used in this study.
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PMID:A study of antitemplate inhibition of mammalian, bacterial and viral DNA polymerases by 2- and 2'-substituted derivatives of polyadenylic acid. 697 88

The specific activity of DNA polymerase (90% alpha) was determined in nine "neoplastoid" cell lines (Martin and Sprague, 1973) and in three different strains of HDF (human diploid fibroblast-like cells), all examined in logarithmic phases of growth. This was compared to the ability of each cell type to "rescue" (reinitiate DNA synthesis in) senescent HDF cells subsequent to polyethylene glycol-mediated cell fusions. A sharp "threshold" value of DNA polymerase activity was observed below which reinitiation of DNA synthesis in heterokaryons with senescent HDF does not occur. This threshold was especially obvious when the specific activity of DNA polymerase (p moles dTTP incorporated per mg protein or per cell) was divided by the percent of S-phase cells present in each culture as determined by flow microfluorometry. Our results indicate that the specific activity of DNA polymerase-alpha (or some other factor tightly coregulated with it) in "recessive" cell types (those unable to rescue senescent cells) is only about two times this theoretical "threshold" value, and that fusion of recessive cell types to senescent HDF cells reduces the specific activity in the heterokaryon to below this minimum, thus preventing the cells from entering S phase.
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PMID:Evidence that a critical threshold of DNA polymerase-alpha activity may be required for the initiation of DNA synthesis in mammalian cell heterokaryons. 713 Feb 87


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