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)

Both E. coli and calf thymus DNA polymerase can be phosphorylated by cAMP-dependent protein kinase and phosphorylation appears to stimulate the DNA polymerase reaction. Conversely, dephosphorylation of the polymerase molecule, by a protein phosphatase, inhibits the polymerase reaction.
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PMID:Phosphorylation of DNA polymerase. 17 41

The Mr = 38,300 polypeptide of the purified recombinant rat DNA polymerase beta served as an excellent substrate for protein kinase C (PKC) in vitro but not for the catalytic subunit of cAMP-dependent protein kinase. The phosphorylation by PKC resulted in inactivation of DNA polymerase beta activity, and recovery was achieved by dephosphorylation with alkaline phosphatase. Since the phosphorylated DNA polymerase beta was retained with use of a single-stranded DNA-cellulose column, inactivation might occur at a site different from that for the DNA binding. Amino acid sequence analysis of the phosphopeptides revealed that the phosphorylated sites were 2 serine residues at positions 44 and 55 from the NH2 terminus, either or both of which might be involved in the catalytic activity of DNA polymerase beta. Thus, the inactivation of the DNA repair enzyme, DNA polymerase beta, by PKC may be an important process in the modification of DNA metabolism in the nucleus through signal transduction processes.
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PMID:Inactivation of DNA polymerase beta by in vitro phosphorylation with protein kinase C. 204 Jun 2

We observed that lipopolysaccharide (LPS, 1 micrograms/ml) can suppress [3H]thymidine incorporation into acid-insoluble fraction in a mouse macrophage cell line J774 (over 70% at 6 h) without affecting the uptake of [3H]thymidine or DNA polymerase activity. Paralleling this suppression, a decrease in the thymidine kinase (TK) activity, but not of thymidine monophosphate (TMP) kinase and thymidine diphosphate (TDP) kinase, was observed. LPS dose-dependently increased intracellular cAMP levels to about 3.5-times basal at 6 h, proportionally to the decrease of the TK activity. Elevation of intracellular cAMP by several reagents also decreased TK activity. Apparently LPS treatment elevates cAMP concentration by decreasing the low Km cAMP phosphodiesterase activity (58% at 6 h). The time course of cAMP-dependent protein kinase (PK-A) activity during the first 6 h after LPS treatment correlated with that of cAMP concentration. Treatment with a PK-A inhibitor restored about 63% of LPS-induced reduction of TK activity at 6 h. At longer times, however, there was a discrepancy between the change of cAMP concentration or PK-A activity and the reduction of TK activity. Therefore, protein kinase activation caused by the accumulation of intracellular cAMP probably triggers some mechanism responsible for the reduction of the TK activity.
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PMID:The role of cyclic AMP in the lipopolysaccharide-induced suppression of thymidine kinase activity in macrophage. 769 50

Treatment of hamster cells in culture with the DNA alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induces DNA polymerase beta (beta-pol) gene expression and cellular levels of the enzyme. Transcriptional activity of a cloned beta-pol promoter in transient expression assays is also stimulated. Among the requirements for these responses are methylation damage to genomic DNA, cellular cAMP-dependent protein kinase, and the ATF/CREB site of the cloned beta-pol promoter. In the present study, HeLa cell nuclear extract from MNNG-treated cells was much more active in an in vitro transcription assay than nuclear extract from normal cells. By using an oligonucleotide affinity column to deplete the nuclear extract of ATF/CREB, we showed that the difference was due to ATF/CREB activator. Purified ATF/CREB activator from MNNG-treated cells was approximately 10-fold more active than ATF/CREB purified from normal cells as a transcriptional activator for the depleted nuclear extract. ATF/CREB in the extract from normal cells is known to activate in vitro transcription by increasing the rate of promoter clearance [Narayan, S., Widen, S. G., Beard, W. A., & Wilson, S. H. (1994) J. Biol. Chem. 269, 12755-12763]. With ATF/CREB from MNNG-treated cells, the amount of preinitiation complex formed was much greater than with ATF/CREB from normal cells, and the kinetics of both the closed to open preinitiation complex isomerization and promoter clearance were altered. These results indicate that the mechanism of transcriptional activation secondary to DNA alkylation damage is recruitment of more preinitiation complex and alteration of the kinetic scheme of transcription initiation.
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PMID:DNA damage-induced transcriptional activation of a human DNA polymerase beta chimeric promoter: recruitment of preinitiation complex in vitro by ATF/CREB. 781 26