Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ninety hypoxanthine phosphoribosyltransferase-deficient mutants were isolated from lymphocytes of 31 individuals drawn from both control populations and populations exposed to low doses of ionizing radiation. Southern analysis of the DNA revealed altered hybridization patterns in 15 mutants. Of these, 14 changes consisted of deletions of 2 to 40 kilobases or more.
Mol Cell Biol 1987 Feb
PMID:Molecular characterization of 15 rearrangements among 90 human in vivo somatic mutants shows that deletions predominate. 382 35

Two protocols have been developed, both of which utilize the thymidine analog 5-bromodeoxyuridine (BrdUrd) to induce mutations in mammalian cells in culture (E. R. Kaufman and R. L. Davidson, Proc. Natl. Acad. Sci. USA 75:4982-4986, 1978; E. R. Kaufman, Mol. Cell. Biol. 4:2449-2454, 1984). The first protocol, termed incorporational (INC) mutagenesis, utilizes high concentrations of BrdUrd in the culture medium to generate a high intracellular ratio of BrdUTP/dCTP. The second protocol, termed replicational (REP) mutagenesis, entails the incorporation of BrdUrd into DNA under nonmutagenic conditions, the removal of all BrdUrd from the culture medium, and the subsequent replication of the bromouracil-containing DNA in the presence of high intracellular levels of dTTP and dGTP. Genetic studies using reversion analysis at the hypoxanthine-guanine phosphoribosyltransferase locus were used to determine whether the mechanisms of these two BrdUrd mutagenesis protocols had enough specificity to be distinguishable by their ability to revert various mutants. The results of these studies indicated that (i) mutants induced by INC mutagenesis were induced to revert only by REP mutagenesis and not by INC mutagenesis, (ii) mutants induced by REP mutagenesis were more efficiently reverted by INC mutagenesis than by REP mutagenesis, and (iii) both spontaneous mutants and mutants induced by the chemical mutagen ethyl methanesulfonate showed a high degree of specificity when tested for reversion by the BrdUrd mutagenesis protocols.
Mol Cell Biol 1985 Nov
PMID:Reversion analysis of mutations induced by 5-bromodeoxyuridine mutagenesis in mammalian cells. 383 41

A pan T-cell antigen with a molecular weight of 120 kilodaltons (kd) is recognized by a monoclonal antibody, Tp120, produced in our laboratories. Two hybrid clones reactive with this Tp120 antibody were established from the fusion between concanavalin A-stimulated human peripheral blood lymphocytes and hypoxanthine-guanine phosphoribosyltransferase-deficient mouse T cell leukemia, BW5147. These two clones were also positive with two other antibodies, 12.1 and T12, both of which detect 120kd pan T-cell antigen. Karyotype analysis showed that one clone retained human chromosomes 6, 7pq-, and 11, and the other maintained chromosomes 11 and 21. As soon as both of these clones lost the chromosome 11, the expression of Tp120 became negative. The presence of human chromosome 11 was confirmed by the isozyme analysis of lactate dehydrogenase-A. The results indicated that the presence of chromosome 11 was essential for expression of 120kd pan T-cell antigen.
Somat Cell Mol Genet 1985 May
PMID:Assignment of gene coding human T-cell differentiation antigen, Tp120, to chromosome 11. 392 29

Two hypoxanthine phosphoribosyltransferase-deficient human cell lines, D98/AH-2 and HT1080-6TG, were stably transfected with pSV2 gpt, a plasmid containing the selectable marker Escherichia coli xanthine-guanine phosphoribosyl transferase (Eco gpt). Hypoxanthine-aminopterin-thymidine-resistant transformants arose with a frequency of ca. 10(-6) and contained mostly single, but occasionally multiple, copies of the plasmid sequences. These transformants actively express the Eco gpt marker. Single chromosomes from two different HT1080 gpt transformants and one D98 gpt transformant, containing the integrated plasmid sequences, were transferred via microcell-mediated chromosome transfer to hypoxanthine phosphoribosyl transferase-deficient mouse A9 cells. The transferred human chromosomes were identified as 2, 4, and 22, by using a combination of G-11 staining, G-banding, isoenzyme analysis, and in situ hybridization. This system is being used to create a library of interspecies microcell hybrid clones, each clone containing a unique single human chromosome in a mouse background. The complete library will represent the entire human karyotype.
Mol Cell Biol 1985 Jan
PMID:Selective transfer of individual human chromosomes to recipient cells. 398 14

An aryl hydrocarbon hydroxylase (AHH)-deficient gene A- mutant of the mouse line Hepa-1 was treated with calcium phosphate precipitates of DNA from Hepa-1, the rat line H4IIEC3, or an A- -human hybrid in which the A- mutation is complemented by the corresponding human gene. AHH+ transfectants were isolated by selection with benzo[ghi]perylene plus near UV. In addition, a gene A- mutant which also carries a mutation for hypoxanthine phosphoribosyltransferase deficiency was treated with the above genomic DNAs together with pSV2-gpt DNA, and cotransfectants were isolated after treatment with both benzo[ghi]pereylene and HAT. All transfectants and cotransfectants were inducible for AHH by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Both transfectants and cotransfectants were unstable during culture, rapidly losing AHH activity. Rat DNA-derived transfectants were probed in Southern blots with a cDNA probe to mouse cytochrome P1-450 that cross-hybridizes to the corresponding rat gene. All rat DNA-derived transfectants contained the rat P1-450 gene. In half of the transfectants, the rat gene was amplified four- to sevenfold. In one transfectant, the rat gene was truncated at the 3' end. The proportion of rat DNA in different transfectants, as determined by hybridization to a rat repetitive sequence, ranged from less than 1% to 5%. AHH activity and the rat P1-450 gene segregated together in subclones of one of the transfectants. These results demonstrate that the A gene is either the structural gene for cytochrome P1-450, or another very closely linked gene. Previous results (O. Hankinson et al., J. Biol. Chem. 260:1790-1795, 1985) favor the former alternative.
Mol Cell Biol 1985 Apr
PMID:Transfection by genomic DNA of cytochrome P1-450 enzymatic activity and inducibility. 399 Jun 91

Comparative Southern hybridization of cDNA probes to DNA from cells carrying either one or four X chromosomes has been used to distinguish sequences derived from the functional locus for hypoxanthine-guanine phosphoribosyltransferase (HPRT) on the X chromosome from four independent HPRT-like autosomal sequences in the human genome. Subfragments of cDNA were then used to orient fragments from the HPRT locus with respect to the mRNA sequence. The chromosomal origin of each of the autosomal sequences was determined by Southern analysis using DNA from a panel of human-Chinese hamster somatic cell hybrids. Two of the HPRT-like sequences were localized to chromosome 11, the third to chromosome 3, and the fourth to the region between p13 and q11 on chromosome 5. Three of these four autosomal sequences were isolated from genomic recombinant libraries and subcloned fragments from each were used as probes to study restriction fragment length polymorphisms (RFLP) at these loci. A RFLP for MspI was found at the HPRT-like locus on chromosome 5 with a 1.3-kb major allele (frequency = 0.8) and a 3.6-kb minor allele (frequency = 0.2).
Somat Cell Mol Genet 1984 Sep
PMID:Organization of the HPRT gene and related sequences in the human genome. 608 58

We have developed a system to study mutations that affect xanthine-guanine phosphoribosyltransferase gene (gpt) expression in hypoxanthine-guanine phosphoribosyltransferase-deficient CHO cells that have been transformed by the plasmid vector pSV2gpt. One isolated transformant, designated AS52, carries a single copy of the Escherichia coli gpt gene stably integrated into the high-molecular-weight DNA and expresses the bacterial gene for the enzyme xanthine-guanine phosphoribosyltransferase. Mutants deficient in this enzyme can be induced in the AS52 cell line by a variety of mutagens, and spontaneous or induced mutants can be selected for resistance to 6-thioguanine (Tgr). Two Tgr clones derived from the AS52 line were analyzed by Southern blot hybridization and were found to contain deletions involving at least a portion of the gpt gene. Because of the small size and stability of the integrated pSV2gpt plasmid, and the well-defined selection protocol for mutant isolation, the AS52 line offers promise as a system suitable for the study of mutation at the molecular level in CHO cells.
Mol Cell Biol 1984 Jul
PMID:Detection of deletion mutations in pSV2gpt-transformed cells. 609 70

Two anonymous X-specific sequences isolated from a genomic library of flowsorted X chromosomal DNA were selected for study because they revealed restriction fragment length polymorphisms in the region Xq26----qter. One sequence, DXS10, detected a two-allele TaqI polymorphic system with allele frequencies of 0.33 and 0.67. The other, 4D-8, defined an MspI polymorphism with allele frequencies of 0.18 and 0.82. DXS10 is tightly linked to the hypoxanthine phosphoribosyltransferase (HPRT) locus with recombination distance theta = O cM at LOD = 5.55 (95% probability limit theta less than 15 cM). DXS10 maps to Xq26 but is not contained within the HPRT locus itself. 4D-8 shows no detectable linkage to the HPRT locus, with maximum likelihood estimate for theta = 50 cM and a LOD score of -2.61 at theta = 5 cM. These two polymorphisms provide additional chromosomal loci for gene mapping by linkage at the distal end of the long arm of the human X chromosome.
Somat Cell Mol Genet 1984 Nov
PMID:Two anonymous X-specific human sequences detecting restriction fragment length polymorphisms in region Xq26----qter. 609 63

Guanine is transported into germinated conidia of Neurospora crassa by the general purine base transport system. Guanine uptake is inhibited by adenine and hypoxanthine but not xanthine. Guanine phosphoribosyltransferase (GPRTase) activity was demonstrated in cell extracts of wild-type germinated conidia. The Km for guanine ranged from 29 to 69 micro M in GPRTase assays; the Ki for hypoxanthine was between 50 and 75 micro M. The kinetics of guanine transport differ considerably from the kinetics of GPRTase, strongly suggesting that the rate-limiting step in guanine accumulation in conidia is not that catalyzed by GPRTase. Efflux of guanine or its metabolites appears to have little importance in the regulation of pools of guanine or guanine nucleotides since very small amounts of 14C label were excreted from wild-type conidia preloaded with [8-14C]guanine. In contrast, excretion of purine bases, hypoxanthine, xanthine, and uric acid appears to be a mechanism for regulation of adenine nucleotide pools (Sabina et al., Mol. Gen. Genet. 173:31-38, 1979). No label from exogenous [8-14C]guanine was ever found in any adenine nucleotides, nucleosides, or the base, adenine, upon high-performance liquid chromatography analysis of acid extracts from germinated conidia of wild-type of xdh-l strains. The 14C label from exogenous [8-14C]guanine was found in GMP, GDP, GTP, and the GDP sugars as well as in XMP. Xanthine and uric acid were also labeled in wild-type extracts. Similar results were obtained with xdh-l extracts except that uric acid was not present. The labeled xanthine and XMP strongly suggest the presence of guanase and xanthine phosphoribosyltransferase in germinated conidia.
 ...
PMID:Guanine uptake and metabolism in Neurospora crassa. 617

Transfer of genetic information can be effected by incubation of cultured eucaryotic cells with isolated metaphase chromosomes. In most cases, a resulting transformed cell contains only a fragment of a donor chromosome. The amount of transferred donor DNA has been quantified in 11 independent mouse A9 transformants by nucleic acid hybridization analysis. Each transformant had been selected for hprt (hypoxanthine phosphoribosyltransferase; EC 2.4.2.8) transfer and contained part of the human X chromosome. A labeled probe of transcribed human X-chromosomal DNA was prepared by hybridization of nick-translated unique-sequence human DNA with whole cellular RNA from a human-mouse hybrid cell line, A9/HRBC2-A, containing a single human chromosome., X. The amount of human X-chromosomal DNA in the transformants was quantitated by comparing the hybridization of this probe with transformant and A9/HRBC2-A DNAs. Two unstable transformants which had a microscopically detectable donor chromosome fragment contained 15% of the human X-chromosomal single-copy DNA. Four other unstable transformants contained 4 to 7% of human X-chromosomal DNA sequences. The transferred DNA was below the level of detection in three other unstable and in all three stable transformants. We conclude that the initial transfer event can introduce a substantial amount of genetic information but only smaller amounts of DNA are stably incorporated by integration.
Mol Cell Biol 1982 Jan
PMID:Measurement of transcribed human X-chromosomal DNA sequences transferred to rodent cells by chromosome-mediated gene transfer. 618 Feb 99


<< Previous 1 2 3 4 5 6 7 8 9 10