Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel mouse gene, Enhancer trap locus 1 (Etl-1), was identified in close proximity to a lacZ enhancer trap integration in the mouse genome showing a specific beta-galactosidase staining pattern during development. In situ analysis revealed a widespread but not ubiquitous expression of Etl-1 throughout development with particularly high levels in the central nervous system and epithelial cells. The amino acid sequence of the Etl-1 protein deduced from the cDNA shows strong similarity, over a stretch of 500 amino acids, to the Drosophila brahma protein involved in the regulation of homeotic genes and to the yeast transcriptional activator protein SNF2/SWI2 as well as to the RAD54 protein and the recently described helicase-related yeast proteins STH1 and MOT1. Etl-1 is the first mammalian member of this group of proteins that are implicated in gene regulation and/or influencing chromatin structure. The homology to the regulatory proteins SNF2/SWI2 and brahma and the expression pattern during embryogenesis suggest that Etl-1 protein might be involved in gene regulating pathways during mouse development.
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PMID:The mouse Enhancer trap locus 1 (Etl-1): a novel mammalian gene related to Drosophila and yeast transcriptional regulator genes. 148 24

The DNA repair and recombination genes of Saccharomyces cerevisiae, RAD52 and RAD54, were transcriptionally induced approximately 10- to 15-fold in sporulating MATa/alpha cells. Congenic MATa/a cells, which did not sporulate, did not show similar increases. Assays of beta-galactosidase activity in strains harboring either a RAD52- or RAD54-lacZ gene fusion indicated that this induction occurred at a time concomitant with a commitment to meiotic recombination, as measured by prototroph formation from his1 heteroalleles.
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PMID:Two DNA repair and recombination genes in Saccharomyces cerevisiae, RAD52 and RAD54, are induced during meiosis. 250 37

The RAD52 and RAD54 genes in the yeast Saccharomyces cerevisiae are involved in both DNA repair and DNA recombination. RAD54 has recently been shown to be inducible by X-rays, while RAD52 is not. To further investigate the regulation of these genes, we constructed gene fusions using 5' regions upstream of the RAD52 and RAD54 genes and a 3'-terminal fragment of the Escherichia coli beta-galactosidase gene. Yeast transformants with either an integrated or an autonomously replicating plasmid containing these fusions expressed beta-galactosidase activity constitutively. In addition, the RAD54 gene fusion was inducible in both haploid and diploid cells in response to the DNA-damaging agents X-rays, UV light, and methyl methanesulfonate, but not in response to heat shock. The RAD52-lacZ gene fusion showed little or no induction in response to X-ray or UV radiation nor methyl methanesulfonate. Typical induction levels for RAD54 in cells exposed to such agents were from 3- to 12-fold, in good agreement with previous mRNA analyses. When MATa cells were arrested in G1 with alpha-factor, RAD54 was still inducible after DNA damage, indicating that the observed induction is independent of the cell cycle. Using a yeast vector containing the EcoRI structural gene fused to the GAL1 promoter, we showed that double-strand breaks alone are sufficient in vivo for induction of RAD54.
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PMID:Regulation of RAD54- and RAD52-lacZ gene fusions in Saccharomyces cerevisiae in response to DNA damage. 355 Apr 29

The relationship between the induction of the genes RAD54 and RNR2 and the induction and repair of specific DNA lesions was studied in the yeast Saccharomyces cerevisiae using Rad54-lacZ and RNR2-lacZ fusion strains. Gene induction was followed by measuring beta-galactosidase activity. At comparable levels of furocoumarin-DNA photoadducts, RAD54 was more effectively induced by bifunctional than by monofunctional furocoumarins indicating that mixtures of monoadducts (MA) and interstrand cross-links (CL) provide a stronger inducing signal than MA. RNR2 induction kinetics were measured in relation to cell growth and survival responses after treatment with the furocoumarins 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP), 3-carbethoxypsoralen (3-CPs), 7-methyl-pyrido[3,4-c]psoralen (MePyPs) and 4,4',6-trimethylangelicin (TMA), benzo[a]pyrene (B(a)P and 1,6-dioxapyrene (1,6-DP) plus UVA, 254 nm UV radiation and cobalt-60 gamma-radiation. Induction of RNR2 took place during the DNA repair period before resumption of cell growth and clearly increased with increasing equitoxic dose levels. Treatments with furocoumarin plus 365 nm radiation (UVA) and 254 nm (UV) radiation were effective inducers whereas gene induction was relatively weak after gamma-radiation and absent after the induction of oxidative damage by B(a)P and 1,6-DP and UVA. The results suggest that it is the specific processing of different DNA lesions that determines the potency of the induction signal. Apparently, DNA lesions such as CL, and probably also closely located MA or pyrimidine dimers in opposite DNA strands involving the formation of double-strand breaks as repair intermediates, are most effective inducers.
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PMID:Induction of the genes RAD54 and RNR2 by various DNA damaging agents in Saccharomyces cerevisiae. 752 Sep 95

The Vitotox and RadarScreen assays were evaluated as early screens for mutagenicity and clastogenicity, respectively. The Vitotox assay is a bacterial reporter assay in Salmonella typhimurium based on the SOS-response, and it contains a luciferase gene under control of the recN promoter. The RadarScreen assay is a RAD54 promoter-linked beta-galactosidase reporter assay in yeast. The expression of this beta-galactosidase can easily be quantified by use of the substrate d-luciferin-o-beta-galactopyranoside, which is converted into galactose and luciferin that can be measured luminometrically. Recently, an ECVAM workgroup defined a list of 20 genotoxic and 42 non-genotoxic compounds [D. Kirkland, P. Kasper, L. Muller, R. Corvi, G. Speit, Recommended lists of genotoxic and non-genotoxic chemicals for assessment of the performance of new or improved genotoxicity tests: a follow-up to an ECVAM workshop, Mutat. Res. 653 (2008) 99-108.] that can be used for the validation and/or optimization of in vitro genotoxicity assays. In the present study, this compound set was used for the validation of the assays. Moreover, an additional set of 192 compounds was used to broaden this validation study. The compounds of this additional set can be classified as non-genotoxins and genotoxins and consists of both in-house and reference compounds. In case of the ECVAM compound list, the results from the Vitotox and RadarScreen assays were compared to the genotoxic/non-genotoxic classification of the compounds in this list. In case of the additionally tested compounds, the results of the Vitotox and RadarScreen assays were compared, respectively, with bacterial mutagenicity (Ames) results or in vitro clastogenicity data obtained in-house or from the literature. The validation with respect to the ECVAM compound list resulted in a sensitivity for both the Vitotox and RadarScreen assay of 70% (14/20). If both assays were combined the sensitivity increased to 85% (17/20). Both tests also gave a low number of false positive results. The specificity of the Vitotox and RadarScreen assays was 93% (39/42) and 83% (35/42), respectively. This resulted in a predictivity of the Vitotox and RadarScreen assay of 85% (53/62) and 79% (49/62), respectively. In case both tests were combined the specificity and the predictivity of the Vitotox and RadarScreen assay turned out to be 81% (34/42) and 82% (51/62), respectively. The results from the additional list of 192 compounds confirmed the results found with the ECVAM compound list. The results from the Vitotox assay showed a high correlation with Ames test of 91% (132/145). Subsequently, the RadarScreen assay had a correlation with in vitro clastogenicity of 76% (93/123). The specificity of the Vitotox assay was 94% (90/96) for Ames test results and that of the RadarScreen assay was 74% (34/46) for clastogenicity. Moreover, the sensitivities of the Vitotox and RadarScreen assays were 86% (42/49) and 77% (59/77), respectively. Implementation of the Vitotox and RadarScreen assays in the early research phase of drug development can lead to fast de-selection for genotoxicity. It is expected that this application will reduce the number of compounds that have a positive score in the regulatory Ames and clastogenicity tests. Moreover, problems with a complete compound class can be foreseen at an early time point in the research phase, which gives more time for issue resolution than late detection of these problems with the regulatory tests.
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PMID:Evaluation of the Vitotox and RadarScreen assays for the rapid assessment of genotoxicity in the early research phase of drug development. 1939 35