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

The PHR1 gene of Saccharomyces cerevisiae encodes a photolyase which repairs specifically and exclusively pyrimidine dimers, the most frequent lesions induced in DNA by far-UV radiation. We have asked whether expression of PHR1 is modulated in response to UV-induced DNA damage and to DNA-damaging agents that induce lesions structurally dissimilar to pyrimidine dimers. Using a PHR1-lacZ fusion gene in which expression of beta-galactosidase is regulated by PHR1 5' regulatory elements, we found that exposure of cells to 254-nm light, 4-nitroquinoline-N-oxide, methyl methanesulfonate, and N-methyl-N'-nitro-N-nitrosoguanidine induced synthesis of increased amounts of fusion protein. In contrast to these DNA-damaging agents, neither heat shock nor exposure to photoreactivating light elicited a response. Induction by far-UV radiation was evident both when the fusion gene was carried on a multicopy plasmid and when it replaced the endogenous chromosomal copy of PHR1, and it was accompanied by an increase in the steady-state concentration of PHR1-lacZ mRNA. Northern (RNA) blot analysis of PHR1 mRNA encoded by the chromosomal locus was consistent with either enhanced transcription of PHR1 after DNA damage or stabilization of the transcripts. Neither the intact PHR1 or RAD2 gene was required for induction. Comparison of the region of PHR1 implicated in regulation of its expression with other damage-inducible genes from yeast cells revealed a common conserved sequence that is present in the PHR1, RAD2, and RNR2 genes and is required for damage inducibility of the latter two genes. These sequences may constitute elements of a damage-responsive regulon in S. cerevisiae.
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PMID:Expression of the yeast PHR1 gene is induced by DNA-damaging agents. 211

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 expression of beta-galactosidase from DNA damage-inducible RNR2-lacZ and RNR3-lacZ fusion constructs was compared in wild-type (WT) and pso5/rad16 mutant strains after treatment with five mutagens/oxidative stressors. While exposure to the mutagens UVC, 4NQO and H2O2 induced expression of the RNR2-lacZ and RNR3-lacZ fusion constructs in two WT strains, treatment with the two oxidative stressors tBOOH and paraquat did not. In the pso5-1 mutant induction of RNR2-lacZ was largely reduced after UVC and H2O2 while there was no significant induction of beta-galactosidase expression after 4NQO treatment for this construct. For RNR3-lacZ there was strongly reduced expression of pso5-1 after UVC and 4NQO while H2O2 failed to induce expression of beta-galactosidase. In the WT strains the ranking of the inducing power of the mutagens at 90% survival (as measured in the pso5-1 mutant) was 4NQO>UVC>H2O2. Though the WT strains were clearly more resistant that the pso5-1 mutant to the two oxidative stressors paraquat and tBOOH, these substances failed to significantly enhance expression of the RNR2-lacZ and RNR3-lacZ fusion constructs in both the WT and the pso5-1 mutant. Our data suggest that Pso5p/Rad16p has a function in the signal transducing pathway controlling DNA damage-inducible components of nucleotide excision repair.
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PMID:The Saccharomyces cerevisiae gene PSO5/RAD16 is involved in the regulation of DNA damage-inducible genes RNR2 and RNR3. 972 15

Yeast-based genotoxicity testing systems can sensitively detect DNA damaging agents in the environment. We have developed a novel "indirect" reporter assay system based on a recombinant yeast containing both a sensor and a reporter plasmid. The sensor plasmid contains a gene encoding the artificial transcription factor of the Escherichia coli LexA DNA binding domain fused to the transcriptional activation domain of yeast Gal4p, which is regulated by the DNA damage-inducible RNR2 promoter. The reporter plasmid contains the E. coli lacZ gene with the LexA binding site in the 5'-upstream region, allowing transcriptional activation by the induced LexA-GAL4 protein. The activity of DNA damage-dependent beta-galactosidase (beta-gal) in the "indirect" reporter assay system was compared with that of a current yeast-based "direct" reporter system. The "indirect" system exhibited 1.5- to 5-fold greater beta-gal activity upon induction by alkylating agents or camptothecin. To increase the sensitivity of the new reporter system further, several deletion yeast strains were tested, and enhanced induction of reporter activity was observed in DNA repair-deficient mag1Delta cells. The "indirect" 96-well microtiter plate assay system is a potentially inexpensive and sensitive method for detecting genotoxic activities in a wide range of compounds, and in polluted environmental samples.
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PMID:A novel yeast-based reporter assay system for the sensitive detection of genotoxic agents mediated by a DNA damage-inducible LexA-GAL4 protein. 1642 25