Disease relevance of uvrA

• Amplification of the uvrA gene product of Escherichia coli to 7% of cellular protein by linkage to the pL promoter of pKC30 [1].
• The genetic end point studied was the reversion of strains of Salmonella typhimurium (TA 100, TA 98, TA 1537) and Escherichia coli (WP2 uvrA), auxotrophic for histidine and tryptophan, respectively [2].
• In addition, a gamma transducing phage carrying the E. coli uvrA+ gene has been shown to also carry the ssbA+ gene and to be capable of producing increased amounts of binding protein [3].
• Although it is established that nucleotide excision repair (NER) significantly protects against cisplatin toxicity, most recombination-deficient strains were as sensitive to the drug as the NER-deficient uvrA mutant [4].
• Identification and characterization of uvrA, a DNA repair gene of Deinococcus radiodurans [5].

High impact information on uvrA

• We confirm that the uvrA gene product is induced by DNA damage in a recA+lexA+-dependent fashion [6].
• We have investigated this possibility further and describe here the generation and characterization of a set of fusions of the lac genes to the promoter of the uvrA gene [6].
• MFD is abolished by mutations in the uvrA, -B, or -C genes, which prevent excision repair, or by a mfd mutation, which reduces the rate of excision but does not affect survival [7].
• The denV gene was found to be expressed, probably from its own promoter, causing pyrimidine dimer incision-deficient uvrA, uvrB, uvrC strains to be rescued by the denV gene [8].
• The cloned uvrA and uvrB genes of Escherichia coli K-12 were amplified by linkage to the PL promoter of plasmid pKC30 [9].

Chemical compound and disease context of uvrA

• The inhibitor of protein synthesis, chloramphenicol, added before irradiation, prevented a small amount of postreplication repair and completely eliminated mutation fixation in E. coli WP2s uvrA [10].
• K-region aziridines of polycyclic aromatic hydrocarbons reverted Salmonella typhimurium his- (TA100, TA98) and Escherichia coli trp- strains (WP2 uvrA), without requiring activation by mammalian enzymes [11].
• N4-Aminocytidine was strongly mutagenic to bacteria (Salmonella typhimurium TA100 and TA1535, and E. coli WP2 uvrA) and to phage (phi X174 am3) [12].
• Soy sauce treated with nitrite was found to be more mutagenic to Escherichia coli WP2 uvrA/pKM101 than Salmonella typhimurium TA100 without S9 mix [13].
• The compounds consisted of 12 chemicals judged previously positive only in E. coli WP2 uvrA/pKM101, 15 of their derivatives, and the 2 well-known mutagens hydrazine and formaldehyde [14].

Biological context of uvrA

• We have constructed a hybrid pKC30-uvrA plasmid (pGHY5003) in which transcription of the uvrA gene can be induced under pL control to amplify the uvrA gene product to 7% of cellular protein [1].
• N'-Methyl-N4-aminocytidine, N'-(2-hydroxyethyl)-N4-aminocytidine and N',N'-dimethyl-N4-aminocytidine showed direct-acting mutagenicity on S. typhimurium TA100 and E. coli WP2 uvrA, tester strains that are sensitive to base-pair substitutions [15].
• Upstream of the uvrA+ gene are two large open reading frames, both of which are directionally divergent from the uvrA+ gene [5].
• Selection for UV resistance, after 5-bromouracil (BU) treatment of E. coli B/r uvrA lexA-102, has yielded derivatives more resistant than lexA but still refractory to UV mutagenesis [16].
• The epoxides were assayed for mutagenicity in the absence of metabolic activation in S. typhimurium TA1535 and E. coli WP2 uvrA and for preferential inhibition of growth of DNA-repair-deficient E. coli [17].

Anatomical context of uvrA

• The results were clear cut: AA did not induce any gene mutations in Salmonella/microsome test systems (TA98, TA100, TA1535, TA1537), Escherichia coli/microsome assay (WP2 uvrA-) up to a dose of 50 mg AA/plate, or in HPRT-locus in Chinese hamster V79H3 cells (AA, 1-7 mM, 24 h treatment) [18].
• High level expression of P 450 1A2 in E. coli WP2 uvrA membranes was determined in SDS-PAGE [19].
• On the other hand, using spheroplasts prepared from E. coli strains, deficient in one of the proteins involved in excision DNA repair (uvrA- or uvrC-) or in post-replication repair (recA-), clear differences between damage originating from OH or H radical attack were found [20].

Associations of uvrA with chemical compounds

• However, chloramphenicol did not affect strand joining: (a) in uvrA bacteria allowed 20 min of growth between irradiation and antibiotic treatment; (b) in nonmutable uvrA exrA bacteria; and (c) in uvrA tif bacteria grown at 42 degrees for 70 min before irradiation [10].
• Three distinct sections of the ultraviolet mutation frequency response (MFR) curve toward tryptophan prototrophy have been demonstrated in Excherichia coli B/r WP2 trp thy and its uvrA derivative in log-phase growth in minimal medium [21].
• Hydroxyurea experiments and thymine starvation of lexA3 and uvrA DNA repair mutants rule out unbalanced growth, the SOS response, and nucleotide excision repair as explanations for TLD [22].
• It is proposed that pyrimidine dimers, although induced, are not significant 365-nm lethal lesions in uvrA and wild-type strains because of their efficient dark repair [23].
• It has been found that tannic acid stimulates the excision repair encoded by the uvrA gene thereby reducing the yield of mutants [24].

Other interactions of uvrA

• In an excision-deficient (uvrA 155) background the yield of UV-induced streptomycin-resistant mutations was lower in gyrB bacteria at all doses; the yield of tryptophan-independent mutations was slightly lower at low doses and slightly higher at high doses [25].

Analytical, diagnostic and therapeutic context of uvrA

• Urinary mutagenic activity detected by the bacterial fluctuation assay, using Salmonella typhimurium TA98 and Escherichia coli WP2 uvrA with and without metabolic activation (S9 mix), was studied in a group of 21 workers exposed to inorganic lead and a control group of 22 non-occupationally exposed subjects [26].
• In the bacterial mutagenicity tests using the Ames Salmonella typhimurium strains TA98, TA100, TA97 and TA102, and Escherichia coli WP2 and WP2 uvrA pKM101 Schistosoma soluble egg antigen and a homogenate of adult Schistosoma worms showed no positive responses either in the presence or in the absence of S9 mix [27].
• Abortus ssb, uvrA, GroES, and GroEL genes into the prokaryotic expression vector pMAL-c2 using PCR [28].

References