Disease relevance of topA

• Escherichia coli strains lacking topoisomerase I (topA mutants) normally fail to grow in the absence of compensatory mutations which are presumed to relax DNA [1].
• The viability of the topA mutants lacking DNA topoisomerase I was thought to depend on the presence of compensatory mutations in Escherichia coli but not Salmonella typhimurium or Shigella flexneri [2].
• Mutations in the supX locus, which result in the absence of DNA topoisomerase I enzyme activity in both Salmonella typhimurium and Escherichia coli, are all selected as suppressors of the leu-500 promoter mutation in S. typhimurium [3].
• Cloning and nucleotide sequence analysis showed that in Helicobacter pylori the gene encoding topoisomerase I (topA) lies about 170 nucleotides upstream from flaB, a gene encoding one of the two flagellin proteins that is required for virulence [4].

High impact information on topA

• A topA mutation defective in topoisomerase I could be compensated by increasing both the parC and the parE gene dosage [5].
• Defects in topA allow 99% of cell division events in muk null mutants to proceed without chromosome loss or loss of cell viability [6].
• We show that transcription originating at the gyrA promoter of Escherichia coli is less subject to termination at the lambda Toop terminator (22% read-through) than is transcription originating from either the galOP (1% read-through) or topA (3% read-through) control regions [7].
• Three such E. coli strains, each carrying cloned DNA from episomes with different nonsense-mutant supX alleles, all lacked DNA topoisomerase I activity but expressed antigenic determinants specific to the enzyme; control cells lacked both enzyme activity and antigenic determinants [3].
• These topA(-) cells exhibit cold sensitivity in their growth, however, and this cold sensitivity phenotype appears to be caused by excessive negative supercoiling of intracellular DNA [2].

Chemical compound and disease context of topA

• Novobiocin-dependent topA deletion mutants of Escherichia coli [8].
• Deletion of topA in Escherichia coli was found to result in a higher level of killing after treatment with either hydrogen peroxide or N-ethylmaleimide [9].

Biological context of topA

• Our results suggest that topA activation by Fis is an important component of the Escherichia coli response to oxidative stress [10].
• The peroxide-dependent topA P1 activation is independent of oxyR, but is mediated by Fis. This nucleoid-associated protein binds to the promoter region of topA [10].
• The P3 promoter that is active on the plasmid was not utilized at the chromosomal topA gene under the conditions employed [11].
• Complete nucleotide sequence of the topA gene encoding Escherichia coli DNA topoisomerase I [12].
• When cells started to enter stationary phase, promoter Px1 gradually became the major transcription initiation site for topA, while transcription from promoters P2 and P4 decreased [11].

Associations of topA with chemical compounds

• Not all sites were equally sensitive to oxolinic acid concentration, some sites exhibited an altered cleavage frequency when the gyrB225 delta topA mutant strain DM800 was compared with wild-type cells, and coumermycin selectively changed the cleavage frequency at a few sites in the mutant strain DM800 [13].
• In quinolone-susceptible cells (top+ gyr+) as well as in topA mutants and in gyrB mutants, plasmid DNA was relaxed after the addition of ciprofloxacin [14].
• This DNA relaxation was not observed in a topA mutant, suggesting that this relaxation by chlorpromazine in vivo is catalysed by topoisomerase I [15].
• We show that P1-mediated transduction of delta topA in the presence of sublethal concentrations of novobiocin, an inhibitor of the DNA gyrase B subunit, yields uncompensated Top- isolates which are dependent on novobiocin for optimum growth [8].
• However, the reaction was inhibited by nalidixic acid or by oxolinic acid in the topA mutant and the reaction was resistant to nalidixic acid in a topA mutant carrying, in addition, the nalA26 mutation [16].

Regulatory relationships of topA

• The effect of the topA mutation could be suppressed by an hns mutation, so topoisomerase I might be required to counteract the effect of H-NS protein on gene expression, in addition to its influence on RpoS-dependent transcription [17].

Other interactions of topA

• The relative abundance of 88 proteins was measured in extracts from three strains of Escherichia coli K-12 that are isogenic except for the topA and gyrB genes [18].
• Isolation of the topB gene encoding DNA topoisomerase III as a multicopy suppressor of topA null mutations in Escherichia coli [19].
• We found that NO was mostly normal in cells with inactivated DNA gyrase or in mukB-null mutants lacking topA, although some suppression of NO was evident in the latter case [20].
• Resistance to tus expression mapped to a mutation in the stop codon of the topA gene (topA869), generating an elongated topoisomerase I protein with a marked reduction in activity [21].
• Northern blot analysis showed that induction of gadA and gadB transcription in stationary phase and at pH 5.5 was decreased in the topA mutant [17].

Analytical, diagnostic and therapeutic context of topA

• A transposon Tn10 insertion in topA, the structural gene of Escherichia coli DNA topoisomerase I, behaves as an excluded marker in genetic crosses with many strains of E. coli [22].
• Western blot analysis showed that the topA mutation did not affect accumulation of RpoS, GadX or GadW proteins [17].

References