Disease relevance of uvrB

• We examined the cellular response of two deoxyribonucleic acid repair systems to treatment with spermidine-nitrite reaction products. uvrB- deficient mutants of Salmonella typhimurium LT2 showed enhanced lethal and mutagenic response to the reaction products [1].
• The plasmid increased the ability of wild-type, polA, and uvrB hosts to support plaque production by UV-irradiated phage, and made strain LT2 hisG46 less sensitive to methyl methane sulfonate and to X rays and more responsive to the mutagenic effect of visible-light irradiation [2].
• 9-Aminoacridine and other acridines appeared similar to the anilinoacridines for the most part, in that frameshift mutagenesis and toxicity appeared to be unaffected by the uvrB mutation or by the presence of plasmid pKM101 [3].
• Phototoxicity was essentially identical in hisC3076, hisD3052 and hisG46 strains; uvrB- excision-repair-deficient bacteria were considerably more susceptible to lethal effects than wild-type parental strains, while the presence of pKM101 had no apparent effect on survival [4].

High impact information on uvrB

• These include the R factor pKM101, which has the SOS-inducible mucAB system; a deletion of the uvrB component of excision repair; and rfa mutations to increase the accessibility of bulky chemicals to the bacteria [5].
• The presence of a uvrB mutation or a recA mutation suppressed the generation of spontaneous deletion revertants to approximately 1/2 [6].
• On the other hand, the DNA damage does not contribute significantly to the cytotoxicity caused by the treatment as an excision repair deficiency (uvrB) has no influence on cell killing [7].
• The garA gene mapped near gal and uvrB at about 18 map units, and the garB gene mapped near purC at about 49 map units [8].
• The uvrB gene product is involved in the excision repair of bulky DNA adducts, and the mutMST gene encodes 8-oxoguanine (8-oxoG) DNA glycosylase, which removes 8-oxoG from DNA [9].

Chemical compound and disease context of uvrB

• Group A compounds (nitracrine and its Cl, F, Me and OMe derivatives) were very toxic to bacteria, and uvrB and recA deletions enhanced toxicity by 10-80-fold [10].
• The simple reversible intercalating agents isopropyl-oxazolopyridocarbazole and 9-aminoacridine have been found to induce frameshift -1 mutations at a much lower level in Salmonella typhimurium delta uvrB TA 1537 than in the uvr+ wild type TA 1977 strain [11].
• Three strains of Salmonella typhimurium carrying frameshift mutations affectin g the histidine genes (hisC3076, hisD3052 and hisC207) showed increased sensitivity to mutagenesis by ICR-191 (as judged by measuring back mutation to prototrophy), if they were made deficient in excision repair by deleting the uvrB gene [12].
• The enhanced sensitivity of some Salmonella typhimurium strains to the mutagenic action of a number of chemicals appears to be due to the defect in the uvrB gene product and not to an inability to produce H-2-S or to the absence of formic acid hydrogenlyase which also characterizes these strains [13].
• Vanillin (VAN) and cinnamaldehyde (CIN) are dietary antimutagens that, when added to assay plates, reduced the spontaneous mutant frequency in Salmonella typhimurium strain TA104 (hisG428, rfa, uvrB, pKM101) by 50% [14].

Biological context of uvrB

• Exceptions were ICR191, 3-NO2-acridine and 1- or 3-NO2-anilinoacridine derivatives in which mutagenesis was increased in uvrB strains and also when pKM101 was present [3].
• The base-pair substitution Salmonella typhimurium mutant hisG46 and the hisG46-bearing uvrB excision-repair-deficient mutants TA100, TA1530, TA1535 or TA1950 were used as test organisms [15].
• Reversion of the hisD3052 (frameshift) mutation, on the other hand, was decreased in both uvrB deletion and recA-type strains [16].
• Mitomycin C (MMC)-induced expression of lac-operon fusions to uvrB and to a second SOS locus, din-9, was largely eliminated in topA bacteria [17].
• Ergothioneine blocks the mutagenicity for Salmonella strain TA1950 (hisG46 uvrB) of the nitrosation products of spermidine to an extent that is approximately proportional to the ergothioneine concentration [18].

Anatomical context of uvrB

• The bacteria themselves possessed the deep rough cell wall and uvrB- mutations, thereby minimizing comutagenic effects resulting from transport or DNA repair [19].

Associations of uvrB with chemical compounds

• This synergism was seen both in the induction of 8-azaguanine resistance and the reversion of histidine auxotrophy and was observed in the repair-proficient strain TA1975 as well as its repair-defective (uvrB-) derived strain TA1535 [20].
• The bisulfite-induced base-pair substitution mutations were slightly enhanced by the presence of the plasmid, pKM101, but inhibited by the presence of the uvrB and rfa mutations [21].
• Testing conducted with strains that carry the nonsense mutation in different repair backgrounds indicates that the presence of pKM101 and the deletion of the uvrB gene facilitate the detection of enals and dicarbonyls, but not malondialdehyde, as mutagens [22].
• The alkylating agents SZN and MNNG induced fewer mutations in TA1530 and TA1950 uvrB excision-repair-deficient strains than in the hisG46 excision-proficient strain, indicating that with these mutagens excision-repair is also a mutation-prone process [15].
• The small amount of base-substitution activity exhibited by 2-AAF at the hisG46 allele required the presence of both the pKM101 plasmid and the uvrB mutation [23].

References