Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dimethylnitrosamine maximally inhibits rat liver nuclear RNA synthesis by 50% at a dose of 40 mg/kg of body weight. The inhibition develops during the first 4 hr and persists through the 12th hr. All parenchymal cells of the lever lobule seem to be affected. The decreased RNA synthesis can be accounted for entirely by an inhibition of the RNA polymerase activities quantitatively solubilized and partially purified. A similar inhibition of the polymerase activities was demonstrated in the intact nuclei by inactivating the endogenous template with actinomycin D and assaying the polymerases with an added exogenous template, poly(deoxy-adenylate-deoxythymidylate). Chromatin was prepared by two methods differing in the extent to which they remove the endogenous polymerase activity. Each preparation was transcribed with either added Escherichia coli or partially purified rat liver nucleoplasmic RNA polymerase. With either polymerase or chromatin preparation, no inhibition of the template activity of liver nuclear chromatin isolated from the DMN-treated animals was detected. A similar mechanism of inhibition of RNA synthesis was produced by the action of the methylating agent methyl methanesulfonate on whole nuclei in vitro. The dose-dependent inhibition of RNA synthesis could be accounted for by an inhibition of the RNA polymerase activities quantitatively solubilized and partially purified from the affected nuclei. Chromatin prepared from the methyl methanesulfonate-treated nuclei had a normal template capacity with either E. coli or rat liver nucleoplasmic RNA polymerase. No preferential methylation of the RNA polymerases by [14C]methyl methanesulfonate could be demonstrated. It is concluded that the action of the two methylating agents on RNA metabolism is similar and that the inhibition of liver nuclear RNA synthesis results from inactivation of the RNA polymerases. At the same time, dimethylnitrosamine and methyl methanesulfonate leave the chromatin template intact, at least quantitatively, for the synthesis of RNA. The implications of such an effect on RNA synthesis are discussed.
Cancer Res 1976 May
PMID:Inhibition of rat liver RNA polymerases by action of the methylating agents dimethylnitrosamine in vivo and methyl methanesulfonate in vitro. 17 32

Two-dimensional polyacrylamide gel electrophoresis shows that in nuclei of Novikoff hepatoma ascites cells there are approximately 75 proteins in the chromatin fraction soluble in 3 M NaCl:7 M urea. Dialysis of this fraction to an ionic strength of 0.15 produces a soluble fraction and a precipitate. The proteins in the soluble fraction have been reported to be active in gene control. Antibodies to the soluble fraction distribute diffusely throughout the nucleus, and antibodies to the precipitate localized primarily in the nucleolus and the nuclear ribonucleoprotein network. The nucleolar proteins differ from the extranucleolar proteins in antigenicity and labeling patterns. The development of methods for isolation, purification, and identification of nuclear proteins provided the opportunity for analysis of chromatin antigens in tumor cells. Utilizing two-dimensional preparative polyacrylamide gel techniques as well as conventional procedures, several nuclear proteins have been isolated in electrophoretically homogeneous states including protein A-24, a histone-like nonhistone protein; C-14, a protein that stimulates nucleolar RNA polymerase; and a chromatin antigen soluble in 3 M NaCl:7 M urea that remains soluble after dialysis to 0.15 M NaCl to precipitate the histones and the DNA. This antigen has been found in the chromatin of both the Novikoff hepatoma and the Walker 256 carcinosarcoma but not in the chromatin of either normal or regenerating liver. It is a nonhistone nuclear protein as indicated by its amino acid analysis in which the ratio of the number of acidic to basic amino acids is approximately 1.4. Further studies are in progress on the function and structure of this chromatin protein. As an approach to analysis of relative rates of synthesis of this antigen and otherproteins, the products of translation of messenger RNA of Novikoff hepatoma and normal liver are being analyzed by autoradiography of two-dimensional electrophoretic gels.
Cancer Res 1976 Sep
PMID:Antigenically active nonhistone chromatin proteins in cancer cells. 18 49

During eight successive isologous passages of hepatoma induced in male C3HA mice by N-nitrosodiethylamine, no common features of tumor progression were observed, although both the mitotic pattern and ploidy differed from generation to generation. These additional cytologic criteria allowed the biochemical examination of material least changed due to tumor progression. Tumor nDNA's were characterized by greater actinomycin D (AD)- and acridine orange (AO)-binding abilities than were normal nDNA's; this could have resulted from a higher proportion of double-stranded regions in tumor DNA. Isolated tumor deoxyribonucleoprotein had both lower template activity in an RNA polymerase system and fewer AD- and AO-binding sites, when compared with the activity and sites from normal mouse liver. RNA-DNA hybridization data with the above-mentioned findings showed that in hepatoma, part of the nuclear genome was repressed. Also, RNA "new classes" appeared and a certain proportion of nuclear genes controlling mitochondrial protein biosynthesis were derepressed in tumor mitochondria. The hybridization of mitochondrial RNA (mtRNA) and DNA revealed new classes of pulse-labeled RNA's in in vitro-incubated liver mitochondria that were absent from intact cell organelles; the hybridization properties of in vivo- and in vitro-formed hepatoma mtRNA's were similar. Competition and hybridization experiments demonstrated that in tumor mitochondria in vivo, some new classes of RNA existed. Hepatoma mitochondrial mRNA had a higher metabolic stability than did normal mRNA.
J Natl Cancer Inst 1976 Jul
PMID:Nucleic acids from subcellular fractions of N-nitrosodiethylamine-induced hepatoma in mice. 18 62

The strands of the polyoma genome coding for early and late viral RNA were separated by means of asymmetric cRNA synthesized under high salt conditions by Escherichia coli RNA polymerase. Each strand was then employed in RNA-DNA hybridization experiments to determine the degree to which it is transcribed in transformed cells under several conditions. Except for a concanavalin-A-selected revertant, approximately one-quarter of the early strand was expressed in all of the situations investigated. In contrast, while no significant late strand transcription was detected in transformed cells in culture, the tumors induced by these cells contained transcripts complementary to about 12% of this strand. The results are discussed in terms of current knowledge of the amount of the virus genome required to transform cells.
Int J Cancer 1977 Feb 15
PMID:Polyoma genome transcription in transformed mouse cells growing in culture and as tumors in syngeneic mice. 19 Jan 75

A single peak of DNA polymerase activity was detectable by phosphocellulose chromatography of leukemic guinea pig lymphoblast whole cell extracts. The inability to detect multiple peaks of activity as described with other cell types is shown to be due to the insolubility of a large proportion of the DNA polymerase activity under the extraction condition used. Multiple forms of DNA polymerase with different template specificities were recognized in extracts of the subcellular fractions of these cells after chromatography on phosphocellulose and DEAE cellulose. On Sephadex G-200 gel filtration these enzymes had apparent molecular weights in excess of 140,000 daltons. No RNA polymerase (reverse transcriptase) was detected in any subcellular fraction despite the presence of oncornavirus like particles in these cells.
Cancer Biochem Biophys 1978
PMID:Studies of the template preference and other characteristics of the DNA polymerases of leukemic guinea pig lymphoblasts. 29

The effects of cordycepin (3'-deoxyadenosine) and cordycepin triphosphate on phosphorylation of non-histone chromosomal proteins were assessed in isolated hepatic nuclei in vitro. Cordycepin and cordycepin triphosphate competitively inhibited phosphorylation of urea-soluble nuclear proteins with a Ki of 1.2 X 10(-3) and 8 X 10(-5) M, respectively. Isoelectric focusing of urea-soluble proteins indicated that inhibition occurred predominantly in nuclear proteins with isoelectric points of pH 4 to 7. Quaternary aminoethyl-Sephadex chromatography of extracts of nuclei incubated with cordycepin and cordycepin triphosphate also showed inhibition of phosphorylation of non-histone chromosomal proteins with similar isoelectric points, although greater resolution of proteins with isoelectric points of pH 6 to 7 was achieved. RNA polymerase I and II were not affected by cordycepin and cordycepin triphosphate after quaternary aminoethyl-Sephadex chromatography of nuclear extracts incubated with either agent. However, RNA polymerase I and II in isolated nuclei were competitively inhibited by cordycepin triphosphate but not by cordycepin. These results suggest that cordycepin triphosphate, and perhaps cordycepin too, may affect transcription via interference with the phosphorylation of non-histone chromosomal proteins.
Cancer Res 1978 Apr
PMID:Inhibition of the phosphorylation of non-histone chromosomal proteins of rat liver by cordycepin and cordycepin triphosphate. 30 21

Eight 10-substituted benzo[b][1,5]naphthyridine derivatives containing N-(pyrrolidino)alkylamines, methanesulfonanilides, and aminoacetanilides were prepared, and their binding with DNA was studied by (a) Tm measurements and (b) the effect on DNA-dependent RNA polymerase in vitro. In addition, they were evaluated as antineoplastic agents in the P-388 test. None of the compounds exhibited anti-cancer activity.
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PMID:Synthesis and biological activities of 10-substituted benzo[b][1,5]naphthyridines. 34 48

Purine riboside (nebularine, 9-beta-ribofuranosylpurine) is a naturally occurring base analog which closely resembles adenosine. It inhibits carcinogenic growth. Purine riboside strongly inhibits RNA and DNA synthesis in different cancer ascites cells. Gel electrophoretic analysis of RNA synthesis in vivo in the presence of purine riboside shows the ribosomal components to be inhibited the most. A method for assaying purine riboside or its phosphates intracellularly has been devised, and by using this it has been shown that purine riboside is extensively phosphorylated in the cells. The triphosphate derivative of purine riboside has been isolated and tested in the Escherichia coli RNA polymerase assay. It appears not to be incorporated into this type of RNA and to competitively inhibit this reaction with regard to ATP.
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PMID:Effects of purine riboside on nucleic acid synthesis in ascites cells. 35 98

The effects of 4'-epi-daunorubicin, 4'-epi-adriamycin, and the corresponding beta anomers on the in vitro activity of Escherichia coli DNA polymerase I and RNA polymerase were determined and compared with the effects of the parent compounds. The observed effects parallel the cytotoxic activities, assayed by inhibition of mouse embryo fibroblast proliferation, and the inhibitory activities on DNA synthesis in cultured cells. The data indicate that the inverted configuration at position 1 of the amino sugar results in a markedly reduced biological activity. This conclusion is also substantiated by the data obtained with the beta anomer of adriamycin. A preliminary investigation on the binding properties of these derivatives suggests that the inverted configuration at C-1' produces a significant decrease in the binding to DNA. In contrast, epimerization at position 4' did not produce any significant change in activity. The relationship between biological and biochemical activity and DNA binding properties of the tested compounds are discussed with particularly reference to antitumor activity.
Cancer Res 1976 Jun
PMID:Relationship between activity and amino sugar stereochemistry of daunorubicin and adriamycin derivatives. 77 33

This study compares the effects of in vitro modification of native duck reticulocyte DNA by [14C]-N-acetoxy-2-acetylaminofluorene in terms of alterations in DNA secondary structure, ability to reconstitute nucleosome structures in chromatin, and template activity for in vitro transcription. In contrast to the control native DNA, the carcinogen-modified DNA was susceptible to partial digestion by the single-strand-specific endonuclease S1. Depending on the particular conditions, for every [14C]-N-2-acetylaminofluorene residue released, about 5 to 35 base pairs of DNA were also released during the S1 nuclease digestion. Chromatin was reconstituted in vitro utilizing [14C]-N-2-acetylaminofluorene-modified DNA and unmodified chromatin-associated proteins. This reconstituted chromatin showed the same kinetics and extent of digestion by staphylococcal nuclease and similar nucleosome profiles on sucrose gradient density centrifugation as those obtained with native chromatin or chromatin reconstituted with unmodified DNA. The carcinogen-modified DNA and also chromatin reconstituted from this DNA showed, however, marked reductions in their abilities to serve as templates for transcription with Escherichia coli RNA polymerase. These results suggest that the covalent binding of N-2-acetylaminofluorene to DNA produces localized regions of denaturation in the DNA and that this is associated with a marked impairment in template activity during transcription. This modification, however, does not grossly affect the ability of the DNA to interact with chromosomal proteins to form apparently normal nucleosome structures.
Cancer Res 1977 Mar
PMID:Effect of N-2-acetylaminofluorene modification on the structure and template activity of DNA and reconstituted chromatin. 83 69


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