Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have used a polymerase chain reaction (PCR)-based exon screening assay to determine the spectrum of spontaneous hypoxanthine phosphoribosyltransferase (hprt) gene mutations occurring in an aphidicolin-resistant V79 Chinese hamster cell line (designated Aphr-4-2) that contains a mutant DNA polymerase-alpha and displays a spontaneous mutator phenotype. PCR analyses of 71 independent, 6-thioguanine (TG)-resistant sublines isolated from Aphr-4-2 or parental V79-743X cells using hprt exon 3- and exon 9-specific oligonucleotide primer pairs revealed the loss of exon 3 or 9 from 6 of 60 Aphr-4-2 derived-, and from 1 of 11 parental V79-derived, TG-resistant mutants. Exons 3 and 9 were both lost from 5 of 60 Aphr-4-2-derived mutants, while none of the 11 V79-derived mutants had lost both exons. The results of these PCR-screening assays were further corroborated by Southern and Northern blot hybridization analyses of 28 mutants: 22 of 28 mutants contained an intact hprt gene by Southern analysis; of these 22 mutants 6 of 11 Aphr-4-2-derived mutants contained either reduced or undetectable steady state mRNA levels in contrast to all 11 V79-derived mutants that contained normal amounts of a normal-sized hprt mRNA. The results of our PCR and blot hybridization analyses indicate that the rates of base substitution and deletion mutagenesis are elevated in Aphr-4-2 cells, and suggest that DNA polymerase-alpha may play a role in determining the rate of different molecular types of spontaneous mutations in vivo.
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PMID:Spectrum of spontaneous mutation in animal cells containing an aphidicolin-resistant DNA polymerase alpha. 768 82

The expression of seven enzymes involved in the biosynthesis of DNA was measured in HL-60 promyelocytic leukemia cells treated with dimethylsulfoxide (DMSO) or all-trans retinoic acid (RA) to gain information on their role in the termination of proliferation in cells undergoing granulocytic differentiation. The steady-state levels of the mRNAs for topoisomerase I, topoisomerase II. DNA polymerase-alpha, thymidylate synthase, thymidine kinase and hypoxanthine-guanine phosphoribosyltransferase progressively declined from day 3 to day 7 of exposure to the polar solvent or the retinoid suggesting that the expression of these enzymes is coordinately regulated. In contrast, a pronounced difference between the two inducers of differentiation occurred in the expression of the mRNA of the M2 subunit of ribonucleotide reductase, with DMSO causing virtually complete inhibition of the expression of the M2 subunit of the enzyme from day 5 through day 7, with no change in the steady-state levels of the mRNA being produced by retinoic acid. Measurement of the enzymatic activities of two of these catalysts, thymidylate synthase and thymidine kinase, in cells exposed to the two inducers of maturation corroborated the findings at the level of the mRNAs, with corresponding decreases in the activity of these enzymes. The findings collectively demonstrate that the down-regulation of the expression of a relatively wide variety of enzymes involved in DNA replication occurs as late events in the granulocytic differentiation of HL-60 cells, ensuring that cellular replication cannot occur in terminally differentiated cells.
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PMID:Regulation of the expression of enzymes involved in the replication of DNA in chemically-induced granulocytic differentiation of HL-60 leukemia cells. 968 95