Gene Symbol: parE
Description: DNA topoisomerase IV, subunit B
Alias: ECK3021, JW2998, nfxD
Species: Escherichia coli str. K-12 substr. MG1655

Top Publications

  1. Crisona N, Strick T, Bensimon D, Croquette V, Cozzarelli N. Preferential relaxation of positively supercoiled DNA by E. coli topoisomerase IV in single-molecule and ensemble measurements. Genes Dev. 2000;14:2881-92 pubmed
    ..They also show that the rate of supercoil relaxation by topo IV is several orders of magnitude faster than hitherto appreciated, so that a single enzyme may suffice at each replication fork. ..
  2. Zechiedrich E, Cozzarelli N. Roles of topoisomerase IV and DNA gyrase in DNA unlinking during replication in Escherichia coli. Genes Dev. 1995;9:2859-69 pubmed
    ..We conclude that catenanes are kinetic intermediates in DNA replication and that the essential role of topo IV is to unlink daughter replicons. ..
  3. Zechiedrich E, Khodursky A, Cozzarelli N. Topoisomerase IV, not gyrase, decatenates products of site-specific recombination in Escherichia coli. Genes Dev. 1997;11:2580-92 pubmed
    ..We also discovered that topo IV has an unexpectedly strong DNA relaxation activity that, together with gyrase and topo I, is able to set the supercoiling levels in Escherichia coli. ..
  4. Lopez C, Yang S, Deibler R, Ray S, Pennington J, Digate R, et al. A role for topoisomerase III in a recombination pathway alternative to RuvABC. Mol Microbiol. 2005;58:80-101 pubmed
    ..These data are consistent with a role for topoisomerase III in disentangling recombination intermediates as an alternative to RuvABC to maintain the stability of the genome. ..
  5. Ullsperger C, Cozzarelli N. Contrasting enzymatic activities of topoisomerase IV and DNA gyrase from Escherichia coli. J Biol Chem. 1996;271:31549-55 pubmed
    ..This ability of Topo IV to selectively unlink catenated molecules mirrors its key role in decatenation of replicating chromosomes in vivo. ..
  6. Hardy C, Cozzarelli N. Alteration of Escherichia coli topoisomerase IV to novobiocin resistance. Antimicrob Agents Chemother. 2003;47:941-7 pubmed
    ..In this work we designed an alteration in the ParE subunit of topo IV at a site homologous to that which confers coumarin resistance in gyrase...
  7. Khodursky A, Cozzarelli N. The mechanism of inhibition of topoisomerase IV by quinolone antibacterials. J Biol Chem. 1998;273:27668-77 pubmed
    ..We interpret our results in terms of distinct but complementary roles of Topo IV and gyrase in DNA replication. ..
  8. Zechiedrich E, Khodursky A, Bachellier S, Schneider R, Chen D, Lilley D, et al. Roles of topoisomerases in maintaining steady-state DNA supercoiling in Escherichia coli. J Biol Chem. 2000;275:8103-13 pubmed
    ..09), greatly stimulating transcription from the supercoiling sensitive leu-500 promoter and increasing the number of supercoils trapped by lambda integrase site-specific recombination. ..
  9. Chen C, Malik M, Snyder M, Drlica K. DNA gyrase and topoisomerase IV on the bacterial chromosome: quinolone-induced DNA cleavage. J Mol Biol. 1996;258:627-37 pubmed
    ..coli. These findings provide a molecular explanation for quinolone action in bacteria and a new way to study topoisomerase IV-chromosome interactions. ..

More Information


  1. Yokochi T, Kato J, Ikeda H. DNA nicking by Escherichia coli topoisomerase IV with a substitution mutation from tyrosine to histidine at the active site. Genes Cells. 1996;1:1069-75 pubmed
    Escherichia coli topoisomerase IV is a type II topoisomerase composed of ParC and ParE subunits and plays a major role in the decatenation of replicated molecules...
  2. Li Y, Wong Y, Ng F, Liu B, Wong Y, Poh Z, et al. Escherichia coli Topoisomerase IV E Subunit and an Inhibitor Binding Mode Revealed by NMR Spectroscopy. J Biol Chem. 2016;291:17743-53 pubmed publisher
  3. Layton J, Foster P. Error-prone DNA polymerase IV is regulated by the heat shock chaperone GroE in Escherichia coli. J Bacteriol. 2005;187:449-57 pubmed
    ..We were unable to show that GroE interacts directly with Pol IV, suggesting that GroE may act indirectly. Together with previous results, these findings indicate that Pol IV is a component of several cellular stress responses. ..
  4. Breines D, Ouabdesselam S, Ng E, Tankovic J, Shah S, Soussy C, et al. Quinolone resistance locus nfxD of Escherichia coli is a mutant allele of the parE gene encoding a subunit of topoisomerase IV. Antimicrob Agents Chemother. 1997;41:175-9 pubmed
    The locus nfxD, which contributes to high-level quinolone resistance in Escherichia coli KF111b (gyrAr nfxB nfxD), is only expressed in the presence of a gyrA mutation, and maps to the region of the parC and parE genes, was outcrossed ..
  5. Hsu Y, Chung M, Li T. Distribution of gyrase and topoisomerase IV on bacterial nucleoid: implications for nucleoid organization. Nucleic Acids Res. 2006;34:3128-38 pubmed
    ..In sum, our study suggests a potential role of Topo IIs in the arrangement of DNA supercoiling loop domains in prokaryotic cells. ..
  6. Madabhushi R, Marians K. Actin homolog MreB affects chromosome segregation by regulating topoisomerase IV in Escherichia coli. Mol Cell. 2009;33:171-80 pubmed publisher
    ..In addition, MreB physically interacts with the ParC subunit of Topo IV. Together, these results may explain how dynamics of the bacterial cytoskeleton are coordinated with the timing of chromosome segregation. ..
  7. Charvin G, Bensimon D, Croquette V. Single-molecule study of DNA unlinking by eukaryotic and prokaryotic type-II topoisomerases. Proc Natl Acad Sci U S A. 2003;100:9820-5 pubmed
  8. Peng H, Marians K. Overexpression and purification of bacterial topoisomerase IV. Methods Mol Biol. 1999;94:163-9 pubmed
  9. Maxwell A, Burton N, O Hagan N. High-throughput assays for DNA gyrase and other topoisomerases. Nucleic Acids Res. 2006;34:e104 pubmed
    ..coli topoisomerase IV. The assays are readily adaptable to other enzymes that change DNA supercoiling (e.g. restriction enzymes) and are suitable for use in a high-throughput format. ..
  10. Peng H, Marians K. Decatenation activity of topoisomerase IV during oriC and pBR322 DNA replication in vitro. Proc Natl Acad Sci U S A. 1993;90:8571-5 pubmed
    Topoisomerase IV (Topo IV), encoded by parC and parE, is required for partition of the daughter chromosomes in Escherichia coli. This enzyme is likely responsible for decatenating the linked daughter chromosomes after replication...
  11. Levine C, Marians K. Identification of dnaX as a high-copy suppressor of the conditional lethal and partition phenotypes of the parE10 allele. J Bacteriol. 1998;180:1232-40 pubmed
    ..In Escherichia coli, topoisomerase IV (Topo IV), encoded by parE and parC, is responsible for decatenation of the two newly formed chromosomes...
  12. Weiss D. Bacterial cell division and the septal ring. Mol Microbiol. 2004;54:588-97 pubmed
    ..Finally, two murein hydrolases, AmiC and EnvC, have been shown to localize to the septal ring of Escherichia coli, where they play an important role in separation of daughter cells. ..
  13. Wang X, Reyes Lamothe R, Sherratt D. Modulation of Escherichia coli sister chromosome cohesion by topoisomerase IV. Genes Dev. 2008;22:2426-33 pubmed publisher
    ..Therefore, we propose that precatenanes, which form as replication progresses by interwinding of newly replicated sister chromosomes, are responsible for E. coli sister chromosome cohesion...
  14. Peng H, Marians K. The interaction of Escherichia coli topoisomerase IV with DNA. J Biol Chem. 1995;270:25286-90 pubmed
    ..In addition, Topo IV preferentially bound supercoiled rather than relaxed DNA. Thus, the DNA binding characteristics of Topo IV are more akin to those of the type II eukaryotic enzymes rather than those of its prokaryotic partner. ..
  15. El Sayyed H, Le Chat L, Lebailly E, Vickridge E, Pages C, Cornet F, et al. Mapping Topoisomerase IV Binding and Activity Sites on the E. coli Genome. PLoS Genet. 2016;12:e1006025 pubmed publisher
    ..These results show that Topo IV, XerCD/dif and MatP are part of a network dedicated to the final step of chromosome management during the cell cycle. ..
  16. Crisona N, Cozzarelli N. Alteration of Escherichia coli topoisomerase IV conformation upon enzyme binding to positively supercoiled DNA. J Biol Chem. 2006;281:18927-32 pubmed
    ..We show that the ParE subunits are in close enough proximity to be cross-linked only when the enzyme is bound to positively supercoiled ..
  17. Furukohri A, Goodman M, Maki H. A dynamic polymerase exchange with Escherichia coli DNA polymerase IV replacing DNA polymerase III on the sliding clamp. J Biol Chem. 2008;283:11260-9 pubmed publisher
    ..Our study suggests a model in which the interaction between pol III* and the beta clamp is mediated by pol IV to ensure that DNA replication proceeds with minimal interruption. ..
  18. Kang S, Han J, Park J, Skarstad K, Hwang D. SeqA protein stimulates the relaxing and decatenating activities of topoisomerase IV. J Biol Chem. 2003;278:48779-85 pubmed
  19. Bellon S, Parsons J, Wei Y, Hayakawa K, Swenson L, Charifson P, et al. Crystal structures of Escherichia coli topoisomerase IV ParE subunit (24 and 43 kilodaltons): a single residue dictates differences in novobiocin potency against topoisomerase IV and DNA gyrase. Antimicrob Agents Chemother. 2004;48:1856-64 pubmed
    ..Here, we report the crystal structures of a 43-kDa N-terminal fragment of Escherichia coli topoisomerase IV ParE subunit complexed with adenylyl-imidodiphosphate at 2...
  20. Bermejo R, Branzei D, Foiani M. Cohesion by topology: sister chromatids interlocked by DNA. Genes Dev. 2008;22:2297-301 pubmed publisher
    ..They propose that DNA precatenanes, arising during replication fork progression, hold sister chromatids together. ..
  21. Levine C, Hiasa H, Marians K. DNA gyrase and topoisomerase IV: biochemical activities, physiological roles during chromosome replication, and drug sensitivities. Biochim Biophys Acta. 1998;1400:29-43 pubmed
    ..These different roles can be attributed to differences in the biochemical properties of the two enzymes. The biochemical activities, physiological roles, and drug sensitivities of the enzymes are reviewed. ..
  22. Peng H, Marians K. Escherichia coli topoisomerase IV. Purification, characterization, subunit structure, and subunit interactions. J Biol Chem. 1993;268:24481-90 pubmed
    DNA sequence analysis of Escherichia coli parC and parE, encoding the subunits of topoisomerase IV (Topo IV) (Kato, J.-I., Suzuki, H., and Ikeda, H. (1992) J. Biol. Chem...
  23. Kato J, Nishimura Y, Imamura R, Niki H, Hiraga S, Suzuki H. New topoisomerase essential for chromosome segregation in E. coli. Cell. 1990;63:393-404 pubmed
    ..this gene were isolated and showed the typical Par phenotype at nonpermissive temperature; thus the gene was named parE. Enhanced relaxation activity of supercoiled plasmid molecules was detected in the combined crude cell lysates ..
  24. Stone M, Bryant Z, Crisona N, Smith S, Vologodskii A, Bustamante C, et al. Chirality sensing by Escherichia coli topoisomerase IV and the mechanism of type II topoisomerases. Proc Natl Acad Sci U S A. 2003;100:8654-9 pubmed
    ..Single-enzyme braid relaxation experiments also provide a direct measure of the processivity of the enzyme and offer insight into its mechanochemical cycle. ..
  25. Charvin G, Strick T, Bensimon D, Croquette V. Topoisomerase IV bends and overtwists DNA upon binding. Biophys J. 2005;89:384-92 pubmed
    ..89 and a strongly bound state (with probability p = 0.11). The methodology introduced here to characterize the Topo IV/DNA complex is very general and could be used to study other DNA/protein complexes. ..
  26. Tran J, Jacoby G, Hooper D. Interaction of the plasmid-encoded quinolone resistance protein QnrA with Escherichia coli topoisomerase IV. Antimicrob Agents Chemother. 2005;49:3050-2 pubmed
    ..With a gel displacement assay, tagged QnrA was shown to bind to topoisomerase IV and its subunits in a reaction that did not depend on the presence of DNA, quinolone, or ATP. ..
  27. Mossessova E, Levine C, Peng H, Nurse P, Bahng S, Marians K. Mutational analysis of Escherichia coli topoisomerase IV. I. Selection of dominant-negative parE alleles. J Biol Chem. 2000;275:4099-103 pubmed
    In order to define regions of ParE, one of the two subunits of topoisomerase IV, that are involved in catalysis during topoisomerization, we developed a selection procedure to isolate dominant-negative parE alleles...
  28. Donachie W. Co-ordinate regulation of the Escherichia coli cell cycle or The cloud of unknowing. Mol Microbiol. 2001;40:779-85 pubmed
    ..A discussion of some aspects of the regulation of chromosome replication, segregation and cell division in Escherichia coli. ..
  29. Hojgaard A, Szerlong H, Tabor C, Kuempel P. Norfloxacin-induced DNA cleavage occurs at the dif resolvase locus in Escherichia coli and is the result of interaction with topoisomerase IV. Mol Microbiol. 1999;33:1027-36 pubmed
    ..This interaction required XerC and XerD, but did not require the C-terminal region of FtsK or cell division. ..
  30. Moon D, Seol S, Gurung M, Jin J, Choi C, Kim J, et al. Emergence of a new mutation and its accumulation in the topoisomerase IV gene confers high levels of resistance to fluoroquinolones in Escherichia coli isolates. Int J Antimicrob Agents. 2010;35:76-9 pubmed publisher
    ..In this study, we determined mutations in gyrA, gyrB, parC and parE among 57 ciprofloxacin-resistant Escherichia coli isolates from a South Korean hospital and analysed the ..
  31. Versalovic J, Koeuth T, McCabe E, Lupski J. Use of the polymerase chain reaction for physical mapping of Escherichia coli genes. J Bacteriol. 1991;173:5253-5 pubmed
  32. Belotserkovskii B, Arimondo P, Cozzarelli N. Topoisomerase action on short DNA duplexes reveals requirements for gate and transfer DNA segments. J Biol Chem. 2006;281:25407-15 pubmed
    ..Topo IV cleaved the DNA-DNA duplex, but not the DNA-RNA duplex implying that the DNA-RNA duplex can be a T-segment but not a G-segment. ..
  33. Hiraga S. Chromosome and plasmid partition in Escherichia coli. Annu Rev Biochem. 1992;61:283-306 pubmed
  34. Trovatti E, Cotrim C, Garrido S, Barros R, Marchetto R. Peptides based on CcdB protein as novel inhibitors of bacterial topoisomerases. Bioorg Med Chem Lett. 2008;18:6161-4 pubmed publisher
    ..These findings demonstrate that the mechanism by which CcdBET2 inhibits DNA gyrase is different of the mechanism by which inhibits Topo IV. Therefore, CcdBET2 is a new type II topoisomerase inhibitor with specificity for Topo IV. ..
  35. Luzzaro F. [Fluoroquinolones and Gram-negative bacteria: antimicrobial activity and mechanisms of resistance]. Infez Med. 2008;16 Suppl2:5-11 pubmed
    ..have developed resistance mechanisms consisting in some target mutations (GyrA/GyrB for DNA gyrase and ParC/ParE for topoisomerase IV) or in a reduced access to the target itself, by either decreased permeability or augmented ..
  36. Webber M, Piddock L. Quinolone resistance in Escherichia coli. Vet Res. 2001;32:275-84 pubmed
  37. Grossman T, Bartels D, Mullin S, Gross C, Parsons J, Liao Y, et al. Dual targeting of GyrB and ParE by a novel aminobenzimidazole class of antibacterial compounds. Antimicrob Agents Chemother. 2007;51:657-66 pubmed
    ..Sequencing of DNA corresponding to the GyrB and ParE ATP-binding regions in VRT-125853- and VRT-752586-resistant mutants revealed that their primary target in ..
  38. Espeli O, Lee C, Marians K. A physical and functional interaction between Escherichia coli FtsK and topoisomerase IV. J Biol Chem. 2003;278:44639-44 pubmed
    ..Topo IV and FtsK appear to cooperate in the cell as well. Rescue of a parE temperature-sensitive mutation by overproduction of DnaX, which leads to stabilization of the temperature-sensitive ..
  39. Bahng S, Mossessova E, Nurse P, Marians K. Mutational analysis of Escherichia coli topoisomerase IV. III. Identification of a region of parE involved in covalent catalysis. J Biol Chem. 2000;275:4112-7 pubmed
    The products of three dominant-negative alleles of parE, encoding the ATP-binding subunit of topoisomerase IV (Topo IV), were purified and their activities characterized when reconstituted with ParC to form Topo IV...
  40. Paltansing S, Kraakman M, Ras J, Wessels E, Bernards A. Characterization of fluoroquinolone and cephalosporin resistance mechanisms in Enterobacteriaceae isolated in a Dutch teaching hospital reveals the presence of an Escherichia coli ST131 clone with a specific mutation in parE. J Antimicrob Chemother. 2013;68:40-5 pubmed publisher
    ..We sequenced gyrA, gyrB, parC and parE. The presence of plasmid-encoded genes qnrA, qnrB, qnrS, aac(6')-Ib, qepA, bla(TEM), bla(SHV,) bla(OXA), bla(CTX-M) ..
  41. Nolivos S, Upton A, Badrinarayanan A, Müller J, Zawadzka K, Wiktor J, et al. MatP regulates the coordinated action of topoisomerase IV and MukBEF in chromosome segregation. Nat Commun. 2016;7:10466 pubmed publisher
    ..We propose that the interplay between MukBEF and MatP directs chromosome organization in relation to MukBEF clusters and associated topisomerase IV, thereby ensuring timely chromosome unlinking and segregation. ..
  42. Springer A, Schmid M. Molecular characterization of the Salmonella typhimurium parE gene. Nucleic Acids Res. 1993;21:1805-9 pubmed
    The DNA sequence of the wild type S. typhimurium parE gene was determined. The predicted protein has 96.7% amino acid identity with the ParE protein of E...
  43. Espeli O, Levine C, Hassing H, Marians K. Temporal regulation of topoisomerase IV activity in E. coli. Mol Cell. 2003;11:189-201 pubmed
    ..factory, as occurs in wild-type cells, and was instead distributed uniformly on the nucleoid; the distribution of ParE, the other subunit of topoisomerase IV, was unaffected...
  44. Khodursky A, Zechiedrich E, Cozzarelli N. Topoisomerase IV is a target of quinolones in Escherichia coli. Proc Natl Acad Sci U S A. 1995;92:11801-5 pubmed
    ..Our results imply that the quinolone binding pockets of gyrase and topo IV are similar and that substantial levels of drug resistance require mutations in both enzymes. ..
  45. Kato J, Suzuki H, Ikeda H. Purification and characterization of DNA topoisomerase IV in Escherichia coli. J Biol Chem. 1992;267:25676-84 pubmed
    The subunits of topoisomerase IV (topo IV), the ParC and ParE proteins in Escherichia coli, were purified to near homogeneity from the respective overproducers...
  46. Grompone G, Bidnenko V, Ehrlich S, Michel B. PriA is essential for viability of the Escherichia coli topoisomerase IV parE10(Ts) mutant. J Bacteriol. 2004;186:1197-9 pubmed
    ..This lethality is suppressed by the activation of a PriA-independent replication restart pathway (dnaC809 mutation). This result suggests that topo IV acts prior to full-chromosome replication completion. ..