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Gene Review

topA  -  DNA topoisomerase I, omega subunit

Escherichia coli str. K-12 substr. MG1655

Synonyms: ECK1268, JW1266, supX
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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


Biological context of topA


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


  1. DNA supercoiling in Escherichia coli: topA mutations can be suppressed by DNA amplifications involving the tolC locus. Dorman, C.J., Lynch, A.S., Bhriain, N.N., Higgins, C.F. Mol. Microbiol. (1989) [Pubmed]
  2. Viability of Escherichia coli topA mutants lacking DNA topoisomerase I. Stupina, V.A., Wang, J.C. J. Biol. Chem. (2005) [Pubmed]
  3. The Escherichia coli supX locus is topA, the structural gene for DNA topoisomerase I. Margolin, P., Zumstein, L., Sternglanz, R., Wang, J.C. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  4. Topoisomerase I of Helicobacter pylori: juxtaposition with a flagellin gene (flaB) and functional requirement of a fourth zinc finger motif. Suerbaum, S., Brauer-Steppkes, T., Labigne, A., Cameron, B., Drlica, K. Gene (1998) [Pubmed]
  5. New topoisomerase essential for chromosome segregation in E. coli. Kato, J., Nishimura, Y., Imamura, R., Niki, H., Hiraga, S., Suzuki, H. Cell (1990) [Pubmed]
  6. Suppression of chromosome segregation defects of Escherichia coli muk mutants by mutations in topoisomerase I. Sawitzke, J.A., Austin, S. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  7. The unexpected antitermination of gyrA-directed transcripts is enhanced by DNA relaxation. Carty, M., Menzel, R. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  8. Novobiocin-dependent topA deletion mutants of Escherichia coli. Hammond, G.G., Cassidy, P.J., Overbye, K.M. J. Bacteriol. (1991) [Pubmed]
  9. Increased sensitivity to oxidative challenges associated with topA deletion in Escherichia coli. Tse-Dinh, Y.C. J. Bacteriol. (2000) [Pubmed]
  10. Escherichia coli response to hydrogen peroxide: a role for DNA supercoiling, topoisomerase I and Fis. Weinstein-Fischer, D., Elgrably-Weiss, M., Altuvia, S. Mol. Microbiol. (2000) [Pubmed]
  11. Regulation of Escherichia coli topA gene transcription: involvement of a sigmaS-dependent promoter. Qi, H., Menzel, R., Tse-Dinh, Y.C. J. Mol. Biol. (1997) [Pubmed]
  12. Complete nucleotide sequence of the topA gene encoding Escherichia coli DNA topoisomerase I. Tse-Dinh, Y.C., Wang, J.C. J. Mol. Biol. (1986) [Pubmed]
  13. DNA gyrase on the bacterial chromosome. Oxolinic acid-induced DNA cleavage in the dnaA-gyrB region. Franco, R.J., Drlica, K. J. Mol. Biol. (1988) [Pubmed]
  14. Effects of ciprofloxacin on plasmid DNA supercoiling of Escherichia coli topoisomerase I and gyrase mutants. Aleixandre, V., Herrera, G., Urios, A., Blanco, M. Antimicrob. Agents Chemother. (1991) [Pubmed]
  15. Inhibition of Escherichia coli DNA topoisomerase I activity by phospholipids. Mizushima, T., Natori, S., Sekimizu, K. Biochem. J. (1992) [Pubmed]
  16. Identification of DNA topoisomerases involved in immediate and transient DNA relaxation induced by heat shock in Escherichia coli. Ogata, Y., Mizushima, T., Kataoka, K., Miki, T., Sekimizu, K. Mol. Gen. Genet. (1994) [Pubmed]
  17. Loss of topoisomerase I function affects the RpoS-dependent and GAD systems of acid resistance in Escherichia coli. Stewart, N., Feng, J., Liu, X., Chaudhuri, D., Foster, J.W., Drolet, M., Tse-Dinh, Y.C. Microbiology (Reading, Engl.) (2005) [Pubmed]
  18. Topoisomerase mutations affect the relative abundance of many Escherichia coli proteins. Steck, T.R., Franco, R.J., Wang, J.Y., Drlica, K. Mol. Microbiol. (1993) [Pubmed]
  19. Isolation of the topB gene encoding DNA topoisomerase III as a multicopy suppressor of topA null mutations in Escherichia coli. Broccoli, S., Phoenix, P., Drolet, M. Mol. Microbiol. (2000) [Pubmed]
  20. Effects of perturbing nucleoid structure on nucleoid occlusion-mediated toporegulation of FtsZ ring assembly. Sun, Q., Margolin, W. J. Bacteriol. (2004) [Pubmed]
  21. Tus-mediated arrest of DNA replication in Escherichia coli is modulated by DNA supercoiling. Valjavec-Gratian, M., Henderson, T.A., Hill, T.M. Mol. Microbiol. (2005) [Pubmed]
  22. Genetic analysis of mutations that compensate for loss of Escherichia coli DNA topoisomerase I. Raji, A., Zabel, D.J., Laufer, C.S., Depew, R.E. J. Bacteriol. (1985) [Pubmed]
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