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)

Mutagenesis by N-acetoxy-N-trifluoroacetyl-4-aminobiphenyl, a reactive form of the human bladder carcinogen 4-aminobiphenyl (ABP), was studied in Escherichia coli virus M13mp10. N-acetoxy-N-trifluoroacetyl-4-ABP-treated DNA containing 140 lesions/duplex genome, when introduced into excision repair-competent cells induced for SOS mutagenic processing, resulted in a 40-fold increase in mutation frequency over background in the lacZ alpha gene fragment. DNA sequence changes were determined for 20 independent mutants. G-C base pairs were the major targets for base pair substitution mutations, although significant mutagenic activity was also observed at certain A-T base pairs. Deletion and frameshift mutations also were found in this sample. The salient feature of this partial "mutational spectrum" was a hotspot that occurred at position 6357 (amino acid 30 of the beta-galactosidase fragment encoded by M13mp10); this A-T to T-A transversion appeared in 6 of the 20 mutants. The property of ABP to mutate A-T base pairs was consistent with the result that N-hydroxy-ABP reverted Salmonella typhimurium strain TA104, which is presumed to revert primarily due to mutations at these sites. The ability of the major carcinogen-DNA adduct formed by ABP in vivo and in vitro, N-(deoxyguanosin-8-yl)-4-aminobiphenyl, to cause base pair substitution mutations was also investigated. This adduct was positioned specifically in the minus strand at position 6270 in duplex M13mp10 DNA. In the presence of the mutagenesis-enhancing plasmid pGW16 and UV induction of SOS mutagenic processing, it was shown that fewer than 0.02% of the adducts resulted in transition or transversion mutations following transfection of DNA into excision-repair competent cells. Similar results were obtained in uvrA and uvrC backgrounds. Although the major adduct did not cause base substitution mutations under these experimental conditions, the contribution of this lesion to the entire spectrum of mutations in the lacZ alpha fragment seems likely.
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PMID:Specificity of mutagenesis by 4-aminobiphenyl. A possible role for N-(deoxyadenosin-8-yl)-4-aminobiphenyl as a premutational lesion. 304 8

The previously described hybrid plasmid pC7 which carries lacI+O+delta(Z)Y+A+ on a 12.3 X 10(6)-Mr DNA fragment [Teather et al. (1978) Mol. Gen. Genet. 159, 239-248] was partially digested with the restriction endonuclease EcoRI under conditions reducing the recognition sequence to d(A-A-T-T) and ligated to the vector pB322. lac Y-carrying inserts of various sized (Mr 1.5-4.7 X 10(6)) were obtained. Hybrid plasmid pTE18 (2300-base-pair insert) carries part of the I (repressor) gene, the promotor-operator region, part of the Z (beta-galactosidase) gene, the Y (lactose carrier) gene and part of the A (transacetylase) gene. Upon induction of pTE18-harbouring strains the Y-gene product is expressed at a nearly constant rate for several generations and accumulates to a level of 12-16% of the total cytoplasmic membrane protein. Integration into the membrane leads to active carrier as judged by binding and transport measurements.
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PMID:Lactose carrier protein of Escherichia coli. Structure and expression of plasmids carrying the Y gene of the lac operon. 625 Aug 28

The spo0B gene is one of the genes involved in initiation of sporulation of Bacillus subtilis. This gene, previously cloned into the pHV33 shuttle vector, is expressed in Escherichia coli and B. subtilis. We have determined the sequence of 1118 base pairs (bp) of the DNA insert carrying the spo0B gene. The promoter sequence of this gene shows the canonical T-A-T-A-A-T region at 10 bp from the transcriptional start (-10 region) but an unusual sequence, T-T-T-T-C-T-, in the -35 region. The nucleotide sequence shows an open reading frame encoding a 192-amino-acid polypeptide of Mr 22,542, which is close to the molecular weight of the spo0B product synthesized in E. coli minicells. To investigate the regulation of the spo0B gene under a variety of physiological conditions, we constructed an in-frame fusion between the spo0B promoter proximal region and the lacZ gene of E. coli. This hybrid gene was subsequently integrated into the B. subtilis chromosome, and the beta-galactosidase activity was measured. It was found that the spo0B gene is preferentially expressed during exponential growth; it is not induced by exhaustion of the growth medium nor repressed by glucose.
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PMID:Nucleotide sequence of the spo0B gene of Bacillus subtilis and regulation of its expression. 643 29

Androgenetic alopecia (AGA), a hereditary disorder that involves the progressive thinning of hair in a defined pattern, is driven by androgens. The hair follicle dermal papilla (DP) expresses androgen receptors (AR) and plays an important role in the control of normal hair growth. In AGA, it has been proposed that the inhibitory actions of androgens are mediated via the DP although the molecular nature of these interactions is poorly understood. To investigate mechanisms of AGA, we cultured DP cells (DPC) from balding and non-balding scalp and confirmed previous reports that balding DPC grow slower in vitro than non-balding DPC. Loss of proliferative capacity of balding DPC was associated with changes in cell morphology, expression of senescence-associated beta-galactosidase, as well as decreased expression of proliferating cell nuclear antigen and Bmi-1; upregulation of p16(INK4a)/pRb and nuclear expression of markers of oxidative stress and DNA damage including heat shock protein-27, super oxide dismutase catalase, ataxia-telangiectasia-mutated kinase (ATM), and ATM- and Rad3-related protein. Premature senescence of balding DPC in vitro in association with expression of p16(INK4a)/pRB suggests that balding DPC are sensitive to environmental stress and identifies alternative pathways that could lead to novel therapeutic strategies for treatment of AGA.
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PMID:Premature senescence of balding dermal papilla cells in vitro is associated with p16(INK4a) expression. 1798 30