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)

When mouse lymphoma cells (L-1210) are treated with methylnitrosourea, a DNA-damaging agent, polyadenosine diphosphoribose (poly(ADP-ribose)) synthetase activity increases 5-8-fold in 2-3 h, while RNA polymerase activity remains constant for an initial 2 h and then gradually decreases to 25-30% of the control level in 5 h. Both alpha-amanitin-sensitive and -resistant RNA polymerase activities are depressed to the same degree by the treatment with methylnitrosourea. The depression in RNA synthesis is virtually prevented when the treated cells are cultured in the presence of 3-aminobenzamide, a specific inhibitor of poly(ADP-ribose) synthetase. Analyses of the RNA extracted from the cells labeled with [3H]uridine by agarose gel electrophoresis and by poly(U)-Sepharose column chromatography show that the contents of ribosomal precursor RNA and poly(A)-containing RNA are both low in the methylnitrosourea-treated cells as compared with those in the untreated cells and that the reduction in the contents of these kinds of RNA is almost completely prevented by the addition of 3-aminobenzamide to the culture medium. These results suggest that the enhancement of poly(ADP-ribosyl)ation causes the decrease in both synthesis of ribosomal RNA and messenger RNA.
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PMID:Participation of poly(ADP-ribosyl)ation in the depression of RNA synthesis caused by treatment of mouse lymphoma cells with methylnitrosourea. 617 37

When permeabilized hamster fibroblasts were incubated with 4 mM-NAD+, the substrate for poly(ADP-ribose) polymerase, RNA polymerase I activity was inhibited by about 85%. This inhibition was not relieved by prior incubation of cells with 3-aminobenzamide, a potent inhibitor of the poly(ADP-ribose) polymerase. Digestion of cells with pancreatic deoxyribonuclease I resulted in the inhibition of RNA polymerase I by 80% and the activation of poly(ADP-ribose) polymerase by up to 300%; prior incubation with 3-aminobenzamide did not prevent the inhibition of the RNA polymerase activity. No radioactivity was found associated with RNA polymerase I during later stages of purification of this enzyme from permeabilized cells previously incubated with [14C]NAD+. The inhibitory effect of NAD+ on RNA polymerase I was not specific for NAD+, as other small, negatively charged molecules with a nuclear location also inhibited the enzyme. The results do not support the concept of a role for ADP-ribosylation in transcription catalysed by RNA polymerase I.
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PMID:NAD+, ADP-ribosylation and transcription in permeabilized mammalian cells. 628 Jun 77

Events preceding glucocorticoid-induced growth inhibition and cytolysis were studied in CEM-C7 human leukaemic lymphoblasts. Inhibitory effects on uridine and thymidine incorporation and on RNA polymerase A activity preceded cell killing, and may relate to the arrest of the cells in the G1 phase of the cell cycle. An inhibitory effect on RNA polymerase B activity emerged later than the effect on RNA polymerase A; this action may reflect commitment to cell death. Cell death was not apparent within the first 24 hr of steroid treatment but thereafter was associated with extensive DNA fragmentation. The lethal action of dexamethasone in CEM-C7 cells was potentiated by 3-aminobenzamide, an inhibitor of poly(ADP-ribose)polymerase.
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PMID:Temporal relationships between inhibitory effects of glucocorticoids on cells of the CEM-C7 human leukaemic lymphoblast cell line. 689 52

S100 extract prepared from rapidly growing mouse FM3A cells (approx. 5 x 10(5) cells/ml) transcribed ribosomal RNA gene (rDNA) much more actively in vitro than that from stationary phase cells (1-2 x 10(6) cells/ml). When the inactive S100 extract was preincubated with NAD+, rDNA transcriptional activity was restored almost to the level of the active extract. The extract activated with NAD+ exhibited a gel-shift band in the gel mobility shift assay and enhancement of protection of the sequence between -44 and -8 nt from the initiation site from exonuclease III digestion. Such an extract labeled with [32P]NAD+ was analyzed by immunoprecipitation with anti-RNA polymerase I (pol I) antibody; a protein with M(r) 130 kDa was detected. In contrast, the polypeptide was hardly labeled in the active extract. 3-Aminobenzamide, a specific inhibitor of poly ADP-ribosylation, did not inhibit the activation by NAD+. These results suggest that the activation by NAD+ is due to enhancement of the formation of initiation complex by mono ADP-ribosylation of the second-largest subunit (130 kDa) of pol I.
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PMID:Transcription of mouse ribosomal RNA gene with inactive extracts is activated by NAD+ in vitro. 845 71