Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have designed an Ha-ras/thymidine kinase (TK) cassette that permits the incorporation of chemically synthesized adducts within specific domains of the rat Ha-ras protooncogene. This cassette has been used to evaluate the mutagenicity of O6-substituted guanine residues, including O6-methylguanine and O6-benzylguanine, incorporated within the 12th codon of this locus. Mutations were monitored by the ability of these modified Ha-ras DNAs to transform Rat4 TK-cells. Our results indicate that both types of O6-substituted guanines are substantially mutagenic, although the methyl substituent induced a 2-fold higher percentage of transformed Rat4 TK+ colonies than its bulkier benzyl analogue. Interestingly, the mutagenicity of both O6-substituted guanines was found to be independent of their relative position within codon 12, therefore suggesting that the specific activation of Ha-ras oncogenes by GGA----GAA mutations in tumors induced by methylating carcinogens might be due to differences in the accessibility of these guanine residues to the carcinogen rather than to a differential rate of repair. Molecular analysis of the mutations induced by these O6-substituted guanines indicated that O6-methylguanine exclusively induced G----A transitions. In contrast, O6-benzylguanine produced G----C and G----T transversions in addition to G----A transitions. These results suggest that O6-methylguanine and its bulkier analogue O6-benzylguanine may induce mutagenesis by different mechanisms.
 ...
PMID:Molecular analysis of O6-substituted guanine-induced mutagenesis of ras oncogenes. 268 55

Chromosome-mediated gene transfer (CMGT) of the human genes for hypoxanthine phosphoribosyl transferase (HPRT) and cytosol thymidine kinase (TK1) into HPRT deficient mouse A9 cells or TK deficient Swiss mouse 3T3TK- cells was found to occur at frequencies at least one order of magnitude higher than DNA-mediated gene transfer (DMGT). The frequency of CMGT into 3T3TK- cells was reduced by more than an order of magnitude by a posttreatment of the recipient cells with dimethyl sulphoxide (DMSO). After CMGT, expression of the non-selected genes coding for galactokinase (GALK) and acid alpha-glucosidase (GAA), both syntenic with TK1, was observed in a number of transformants. From the pattern of cotransfer, a tentative gene ordering of CENTROMERE-GALK-TK1-GAA on human chromosome 17 was deduced. Chromosome-mediated cotransfer of X-linked human phosphoglycerate kinase (PGK) with HPRT was observed in two out of 33 A9 transformants analysed. DNA-mediated cotransfer of a syntenic gene was only observed for GALK, cotransferred with TK1 in two out of 18 TK+ transformants of mouse LTK- cells. Therefore, with murine cells as recipients of human donor genetic material, CMGT results in a higher frequency of transfer and a higher incidence of cotransfer of syntenic genes than DMGT using cellular DNA in the same cell system.
 ...
PMID:Cotransfer of syntenic human genes into mouse cells using isolated metaphase chromosomes or cellular DNA. 388 35

The pro alpha 1 (I) collagen structural gene (COL1A1), the acid alpha-glucosidase (GAA), and the thymidine kinase (TK) genes, known to be closely linked in man (HSA) and mapped to HSA17, were found syntenic in two Cercopithecoidae species, the baboon (Papio papio, PPA) and the African green monkey (Cercopithecus aethiops, CAE) and assigned to homoeologous chromosomes, PPA16 and CAE19, respectively. The assignment of COL1A1 was obtained using two human cDNA probes. Hind III restriction sites found in man were present in the two species. The particular CAE individual used in the experiment showed a polymorphism for one DNA fragment.
 ...
PMID:Conservation of the human COL1A1-TK-GAA synteny and homoeologous assignment in the African green monkey and the baboon (Cercopithecoidae). 609 58

Previous deletion analysis of the Drosophila hsp70 heat-shock promoter has identified a sequence upstream of the TATA box that is required for heat induction. This region contains homology to other heat-shock promoters, and it was proposed that the common sequence is an important element in the regulation of the heat-shock genes. We have constructed sequences similar to the consensus CT-GAA-TTC-AG from synthetic oligonucleotides and placed them upstream of the TATA box of the herpes virus thymidine kinase gene, in place of the normal upstream promoter element. The resultant genes are heat-inducible both in monkey COS cells and in Xenopus oocytes. We conclude that the transcriptional heat-shock response is mediated by some factor that interacts with this sequence.
 ...
PMID:A synthetic heat-shock promoter element confers heat-inducibility on the herpes simplex virus thymidine kinase gene. 632 71

We have confirmed the localization of human acid alpha-glucosidase (GAA) to 17q21----q25 and of adenosine deaminase (ADA) to 20q13----20qter by examination of hybrid clones derived from a fusion between a human cell line carrying a 17/20 balanced translocation (17pter----17q25::20q13----20qter;20pter-- --20q13::17q25----17qter) and a mouse line deficient in thymidine kinase. These hybrids were constantly maintained in HAT selective media in order to select for the presence of the human thymidine kinase gene on the intact chromosome 17 (17q21----22) or the 17/20 (17pter----17q25::20q13----20qter) translocation chromosome. We detected human GAA by rocket immunoelectrophoresis, using a heterologous antibody raised against human acid alpha-glucosidase. A clone which contained the 17/20 translocation and no intact chromosome 17 was still positive for GAA. This finding confirms the exclusion of GAA from 17q25----17qter reported by Nickel et al. (1982). Combined with earlier results (Weil et al. 1979), GAA can be assigned to 17q21----17q25. A clone which contained only the 17/20 translocation chromosome and no intact chromosome 20 contained ADA. This confirms the previous localization of ADA to 20q13.2----qter by gene dosage studies (Philip et al. 1980).
 ...
PMID:Confirmation of the regional localization of the genes for human acid alpha-glucosidase (GAA) and adenosine deaminase (ADA) by somatic cell hybridization. 637 91

Genomic DNA clones of human acid alpha glucosidase (GAA) and thymidine kinase (TK1) were used to map the exact location and order of these genes on human chromosome 17. Both genes were localized to the 17q25-qter band (17q25.2-q25.3), with GAA distal to TK1. They were also shown to be, respectively, distal and proximal to an anonymous cosmid (cK17.71) previously mapped to this region.
 ...
PMID:Localization and ordering of acid alpha-glucosidase (GAA) and thymidine kinase (TK1) by fluorescence in situ hybridization. 878 92