Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.4.2.7 (adenine phosphoribosyltransferase)
692 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Relative to rabbit erythrocytes, chicken red blood cells exhibit a much greater capacity to utilize [3H]adenine for nucleotide synthesis in vitro, even at 5 degrees C and in the absence of added inorganic phosphate. 2. This difference is largely due to a higher concentration of phosphoribosylpyrophosphate and greater activity of adenine phosphoribosyltransferase in the avian cells. 3. The capacity of avian erythrocytes for utilization of guanine and hypoxanthine is several fold less than that of adenine. 4. The data are consistent with lower activity for hypoxanthine/guanine phosphoribosyltransferase than for adenine phosphoribosyltransferase in intact chicken erythrocytes. 5. The results indicate that reutilization of adenine by chicken erythrocytes may be physiologically significant.
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PMID:Contrast in adenine uptake by chicken and rabbit erythrocytes in vitro. 128 Jan 89

Constitutional loss or inactivation of one copy of a tumor-suppressor gene, as exemplified by hereditary retinoblastoma, increases the propensity for malignancies by reducing the number of events necessary for the complete loss of the negative regulatory function. We developed a selectable mutation assay employing a human lymphoblastoid cell line (LCL) derived from a heterozygous carrier of 2,8-dihydroxyadenine urolithiasis, adenine phosphoribosyltransferase (APRT) deficiency, for dissecting the second step in loss-of-function mutations and for determining the potential of physical and chemical agents for producing such mutations. The mode of mutational events arising in the wild-type allele of the functionally heterozygous APRT gene resembled that reported for tumor-suppressor genes in malignancies in that mitotic non-disjunctions or recombinations as well as deletions prevailed. Ultraviolet light (UV) was much less efficient in inducing these types of mutations than ionizing radiation. A group of autosomal recessive cancer-prone diseases, including xeroderma pigmentosum (XP), has been characterized as being more susceptible to genomic insults, owing to some defects in DNA processing, such as replication, repair, or recombination. This increased genomic instability may accelerate the gain-of-function mutation at a proto-oncogene and/or the loss-of-function mutation at a tumor-suppressor gene. XP complementation group A (XP-A) LCLs were extremely sensitive to UV-mutagenesis at the hypoxanthine phosphoribosyltransferase (HPRT) locus even at equicytotoxic doses. Some unique mechanism may operate in UV-mutagenesis in XP-A. We have succeeded for the first time in rendering XP-A cells tumorigenic in athymic mice by applying multiple exposures to UV and subsequent treatment with TPA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular bases for hereditary cancer-prone diseases. 129 55

A mouse embryonal carcinoma cell line isolated for resistance to the adenine analogue 2,6-diaminopurine (DAP) was found to have near-wild-type levels of adenine phosphoribosyltransferase (APRT) activity in a cell-free assay. This DAP-resistant (DAPr) cell line, termed H29D1, also exhibited near-wild-type levels of adenine accumulation and the ability to grow in medium containing azaserine and adenine. Growth in this medium requires high levels of intracellular APRT activity. Using the polymerase chain reaction (PCR) and the dideoxy chain termination sequencing technique, an A-->G transition was discovered in exon 3 of the aprt gene in H29D1. This mutation resulted in an Arg-to-Gln change at amino acid 87 of the APRT protein that, in turn, resulted in a decreased affinity for adenine. An increased sensitivity of APRT to inhibition by AMP was observed when comparing H29D1 to P19, the parental cell line. Using a transgene containing the A-->G mutation, we demonstrated that this mutation is responsible for the biochemical and cellular phenotypes observed for the H29D1 cell line. The approach used in this study provides a definitive method for linking a mutation to a specific cellular phenotype.
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PMID:Molecular and biochemical elucidation of a cellular phenotype characterized by adenine analogue resistance in the presence of high levels of adenine phosphoribosyltransferase activity. 129 76

When a functional murine adenine phosphoribosyltransferase (aprt) gene linked to bovine papilloma virus (BPV) DNA is transfected into Aprt- L cells, the cells are rendered Aprt+ and the aprt gene persists as an episome. Cotransfection with two BPV vectors, one containing the 5' half of the aprt gene and the other the 3' half of the gene, that share about 300 bp of common sequence in intron 2, produces Aprt+ cells with functional aprt as an episome. Southern blot analysis of low molecular weight DNA derived from Hirt extracts revealed the regeneration of a diagnostic SmaI fragment, consistent with establishment of an episome with functional aprt that was reconstituted as a consequence of recombination. To establish cells with an episomal target for recombination, BPV vectors containing a G418 resistance marker and either the 5' half or 3' half of aprt were transfected into Aprt- L cells. Stably transfected cells, selected by their growth in G418, were in turn transfected with DNA containing the other half of the aprt gene. Following selection of Aprt+ cells, Southern blot and polymerase chain reaction (PCR) analysis of low molecular weight DNA confirmed the presence of a complete episomal aprt gene. The region of DNA shared by the episomal aprt fragment and the transfected aprt half was sequenced after PCR amplification of the reconstituted, episomal gene and was found to be wild type. The region of overlap that serves as the substrate for recombination lies entirely within an intron and can, therefore, tolerate nucleotide substitutions and deletions. The absence of such errors in the sequences examined is consistent with recombination events that are not error prone.
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PMID:Reconstitution of an episomal mouse aprt gene as a consequence of recombination. 131 48

The colony of gray, short-tailed opossums (Monodelphis domestica) at the Southwest Foundation for Biomedical Research, the primary supplier of this species for research purposes, was founded with nine animals trapped in 1978 in the state of Pernambuco, Brazil. Since 1984, 14 newly acquired founders from the state of Paraiba, Brazil have contributed to the gene pool of the colony. The animals from Paraiba and their descendants are significantly larger than the founders from Pernambuco and their descendants. The two groups also differ significantly in several measurements of morphologic traits. The changes in proportional contribution of each founder to the colony, and changes in inbreeding coefficients during the colony's history, are evaluated. Using previously established markers and three newly identified markers (ACP2, APRT, and DIA1), we show that the Paraiba-derived animals differ significantly from the original founders in allele frequencies and heterozygosity. The genetic diversity of the colony has been substantially increased by acquisition of the new founders from Paraiba. The colony is highly polymorphic, with 22.2% of loci surveyed by protein electrophoresis being variable. We conclude that the genetic differences between populations and among projects within the colony should be considered in future colony management procedures and in selection of experimental subjects.
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PMID:Genetic diversity of laboratory gray short-tailed opossums (Monodelphis domestica): effect of newly introduced wild-caught animals. 132 Jan 55

In some biological systems ionizing radiation appears to induce large deletions and rearrangements, while in others point mutations predominate the mutational spectrum. Moreover, while the point mutations are often randomly distributed, some systems exhibit "hot spots." Retroviral shuttle vectors are particularly useful for investigating the basis of these differences since the genetic target can be conveniently analyzed in a variety of host backgrounds and genomic locations. We have studied the mutational specificity of X-rays in a Chinese hamster ovary cell line (CHO) containing a stably integrated retroviral shuttle vector, carrying the CHO aprt cDNA as the genetic target. Cells were irradiated with 7 Gy using a 180 kVp X-ray source. The predominant mutation (87% of all APRT mutants), as determined by Southern analysis, was the complete deletion of the shuttle vector construct. In addition, 23 APRT mutants, carrying an apparently intact shuttle vector, were characterized at the sequence level: 5 were transitions, 9 were transversions, 3 were small deletions or insertions, 4 were frameshifts, and 2 were small rearrangements. Although the type and the location of the point mutations characterized appeared largely random, small deletions, insertions, and frameshifts were frequently associated with direct sequence repeats.
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PMID:Investigation of the mutagenic specificity of X-rays using a retroviral shuttle vector in CHO cells. 133 May 46

Expression plasmids containing the human alpha 1-antitrypsin (alpha 1 AT) promoter fused to either adenine phosphoribosyltransferase (aprt) or xanthine-guanine phosphoribosyltransferase (gpt) coding sequences were sequentially introduced into APRT- HPRT- rat hepatoma cells. Stable transfectants expressing both transgenes were isolated and characterized. Nonexpressing variants were subsequently obtained by selecting against expression of one or both transgenes. Variants isolated by selecting against expression of either transgene alone generally displayed deficiency phenotypes in cis, as only three of 20 clones tested were affected for expression of alpha 1AT mRNA. In contrast, double selection yielded predominantly trans effects: 12 of 14 lines tested showed impaired ability to express their chromosomal alpha 1AT genes. Furthermore, expression of several other liver genes, including the gene encoding the HNF-1 trans-activator, was repressed in many of the variant lines. Thus, double selection using chimeric transgenes is a useful approach for generating variant cell lines deficient in expression of specific mammalian genes.
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PMID:Direct selection of hepatoma cell variants deficient in alpha 1-antitrypsin gene expression. 133 97

We analyzed mutant alleles of adenine phosphoribosyltransferase (APRT) deficiency in Japanese patients. Among 141 defective APRT alleles from 72 different families, 96 (68%), 30 (21%), and 10 (7%) had an ATG to ACG missense mutation at codon 136 (APRT*J allele), TGG to TGA nonsense mutation at codon 98, and duplication of a 4-bp sequence in exon 3, respectively. The disease-causing mutations of only four (3%) of all the alleles among Japanese remain to be elucidated. Thus, a diagnosis can be made for most of the Japanese APRT-deficient patients by identifying only three disease-causing mutations. All of the different alleles with the same mutation had the same haplotype, except for APRT*J alleles, thereby suggesting that alleles with the same mutation in different families were derived from the same ancestral gene. Evidence for a crossover or gene conversion event within the APRT gene was observed in an APRT*J mutant allele. Distribution of mutant alleles encoding APRT deficiency among the Japanese was similar to that seen in cystic fibrosis genes among Caucasians and Tay-Sachs genes among the Ashkenazi Jews.
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PMID:Only three mutations account for almost all defective alleles causing adenine phosphoribosyltransferase deficiency in Japanese patients. 135 80

Early work with adenine phosphoribosyltransferase-deficient mutants of CHO cells suggested that a site existed in the third exon of this gene which was preferentially susceptible to mutation by ethyl methanesulphonate. To determine whether this was real we analysed a large collection of induced mutants, and generated a high-density mutational spectrum for this exon. In addition, 4 sites outside exon 3 were analysed by blot. 37 mutations were found in 19 available sites, six of which were at nucleotide 1365, 1 of 2 sites in the putative hotspot (P less than 0.02). One other site, 1308, also was mutated in 6 cell lines and may also be preferentially mutable.
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PMID:A mutational hotspot in the aprt gene of Chinese hamster cells. 137 32

We analyzed the nature of mutations at the autosomal locus coding for adenine phosphoribosyltransferase (aprt) in human cells to elucidate the process(es) governing mutagenesis at autosomal loci. A human lymphoblastoid cell line, WR10, was found to be heterozygous for mutated allele at the aprt locus, and was used for mutation analyses. By the use of a restriction fragment length polymorphism associated with the aprt locus in WR10 cells, the molecular characteristics of mutations arising spontaneously or induced by gamma-rays were investigated. Eighty-five percent (22/26) of the spontaneous mutant clones and 93% (64/69) of the gamma-ray-induced mutant clones resulted from loss of one of the two aprt alleles. Determination of the dosage of aprt genes in those mutants with allelic losses revealed that approximately half of them retained two copies of the mutated allele. These data suggest that the mutational events leading to APRT deficiency are analogous to those reported for tumor suppressor genes in malignancies.
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PMID:Allelic losses in mutations at the aprt locus of human lymphoblastoid cells. 138 71


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