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)

The effect of several divalent cations on the accuracy of DNA replication in vitro has been examined. Only Be2+ altered the accuracy of DNA synthesis using purified DNA polymerase (DNA nucleotidyltransferase; deoxynucleosidetriphosphate:DNA deoxynucleotidyltransferase; EC 2.7.7.7) from avian myeloblastosis virus. The Be2+-induced base substitutions occurred with all templates and with all nucleotides tested. Analysis of the product by equilibrium density centrifugation and processive hydrolysis with snake venom phosphodiesterase suggested that the noncomplementary nucleotides were present in phosphodiester linkage. Nearest neighbor studies indicated that many of the Be2+-induced errors were present as single base substitutions. The enhancement of error frequency could be duplicated by the pretreatment of the enzyme, but not the template, with Be2+. Glycerol gradient centrifugation dissociated the Be2+-DNA polymerase complex and restored the initial error frequency of the polymerase. Thus, the weak binding of a metal cation to a DNA polymerase could alter the accuracy with which that polymerase copied DNA. Beryllium is a known carcinogen. The potential use of this system as a screening technique to detect chemical mutagens and carcinogens is considered.
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PMID:Metal-induced infidelity during DNA synthesis. 106 82

1. The incorporation of thymidine into DNA of regenerating rat liver was measured at various times after partial hepatectomy. A single intravenous injection of 30mumol of beryllium/kg given immediately after the operation inhibited DNA synthesis 12, 16, 20, 24 and 28h later. 2. The activity of several enzymes critical to DNA synthesis (thymidine kinase, thymidylate kinase, thymidylate synthetase, deoxycytidylate deaminase and DNA polymerase) increased in control rats 20-24h after partial hepatectomy severalfold over the activity found in resting livers. After beryllium treatment this rise in activity was much less and it seemed as if beryllium would partially block the induction of DNA-synthesizing enzymes after partial hepatectomy. 3. Enzymes whose activities do not rise during liver regeneration were not affected by beryllium (aspartate transcarbamoylase, carbamoyl phosphate synthetase, uridine kinase and glucose 6-phosphatase). 4. No evidence was found in vitro that beryllium would specifically inhibit thymidine kinase or DNA polymerase. 5. The time-effect relationship between beryllium administration and thymidine kinase activity in vivo was examined. Measured 24h after partial hepatectomy, thymidine kinase activity was only affected if beryllium was given within the first 9-12h after partial hepatectomy. Beryllium given later, even in greatly increased doses, failed to have any effect on thymidine kinase. The possibility is discussed that beryllium inhibits enzyme induction at the transcriptional level.
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PMID:Effects of beryllium on deoxyribonucleic acid-synthesizing enzymes in regenerating rat liver. 549 75