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Gene Review

Top1  -  Topoisomerase 1

Drosophila melanogaster

Synonyms: CG6146, DNA topoisomerase 1, DNA topoisomerase I, Dmel\CG6146, TOP1, ...
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Disease relevance of Top1


High impact information on Top1

  • The in vivo distribution of topoisomerase I on specific DNA sequences is determined at high resolution in Drosophila cells using a photo-crosslinking method [5].
  • Like RNA polymerase II, topoisomerase I is recruited to heat-shock genes during the heat-shock response [5].
  • The Drosophila ATP-dependent topoisomerase appears to be closely related to E. coli DNA gyrase in that both use a similar mechanism to change the topology of DNA, both require ATP and both are inhibited by the antibiotic novobiocin [6].
  • We have identified a factor, Drosophila Topoisomerase I-interacting RS protein (dTopors) that interacts with the insulator protein complex and is required for gypsy insulator function [7].
  • Although Topo II relaxes left-handed (L) and right-handed (R-) braids similarly at a rate of approximately 2.9 s-1, Topo IV has a marked preference for L-braids, which it relaxes completely and processively at a rate of approximately 2.4 s-1 [1].

Biological context of Top1


Anatomical context of Top1


Associations of Top1 with chemical compounds

  • Drosophila topoisomerase IIIbeta forms a covalent linkage to 5' DNA phosphoryl groups, and the DNA cleavage reaction prefers single-stranded substrate over double-stranded, suggesting an affinity of this enzyme for DNA with non-double-helical structure [16].
  • The top1 coding region contains a new class of opa repeats, encoding clusters of serine residues instead of glutamine repeats usually seen in Drosophila genes of the neurogenic loci [17].
  • The kinase and topoisomerase activities are not separated when the enzyme is subjected to analytical chromatography (phosphocellulose, single-strand DNA agarose, and Sephacryl S-300) and analytical glycerol gradient sedimentation [18].
  • Phosphoamino acid analysis identified phosphoserine and phosphothreonine in polypeptides modified by the topoisomerase-associated protein kinase [18].
  • Calmodulin-dependent protein kinase II, but not cyclic AMP-dependent protein kinase, was also able to phosphorylate the topoisomerase [11].

Physical interactions of Top1

  • Topoisomerase I also interacted with the DNA throughout the transcriptionally active hsp83 gene, including an intron, in both heat-shocked and non-heat-shocked cells [19].

Other interactions of Top1

  • The top3 cDNA encodes an 875-amino acid protein, which is nearly 60% identical to mammalian topoisomerase IIIbeta enzymes [16].
  • These studies suggest that the topo III enzyme behaves as a structure-specific endonuclease in vivo, providing a reversible DNA cleavage activity that is specific for unpaired regions in the DNA [20].
  • The ATPase activity of the topoisomerase was stimulated 17-fold by the presence of negatively supercoiled DNA and approximately 4 molecules of ATP were hydrolyzed/supercoil removed [21].
  • A model for achiasmatic pairing in Drosophila males based upon the combined action of topoisomerase I and a strand transferase is proposed [22].
  • The presence of a putative site for topoisomerase I at the 5' end of the 18S rRNA gene would allow for the exchange between X and Y chromosomes of some 240 subrepeats, the promoter, and the ETS region, leaving the rest of the rDNA unit to evolve along separate chromosomal lineages [23].

Analytical, diagnostic and therapeutic context of Top1


  1. Single-molecule study of DNA unlinking by eukaryotic and prokaryotic type-II topoisomerases. Charvin, G., Bensimon, D., Croquette, V. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  2. Knotting of the circular duplex DNA by type II DNA topoisomerase from Drosophila melanogaster. Hsieh, T. J. Biol. Chem. (1983) [Pubmed]
  3. Loss of drug-stimulated topoisomerase II DNA breaks in living cells is different at two unrelated loci. Binaschi, M., Borgnetto, M.E., Capranico, G. Nucleic Acids Res. (2000) [Pubmed]
  4. Topoisomerase I is essential in Cryptococcus neoformans: role In pathobiology and as an antifungal target. Del Poeta, M., Toffaletti, D.L., Rude, T.H., Dykstra, C.C., Heitman, J., Perfect, J.R. Genetics (1999) [Pubmed]
  5. Topoisomerase I interacts with transcribed regions in Drosophila cells. Gilmour, D.S., Pflugfelder, G., Wang, J.C., Lis, J.T. Cell (1986) [Pubmed]
  6. ATP-dependent DNA topoisonmerase from D. melanogaster reversibly catenates duplex DNA rings. Hsieh, T., Brutlag, D. Cell (1980) [Pubmed]
  7. The ubiquitin ligase dTopors directs the nuclear organization of a chromatin insulator. Capelson, M., Corces, V.G. Mol. Cell (2005) [Pubmed]
  8. Drosophila melanogaster topoisomerase IIIalpha preferentially relaxes a positively or negatively supercoiled bubble substrate and is essential during development. Plank, J.L., Chu, S.H., Pohlhaus, J.R., Wilson-Sali, T., Hsieh, T.S. J. Biol. Chem. (2005) [Pubmed]
  9. Developmental regulation of DNA-topoisomerases during Drosophila embryogenesis. Gemkow, M.J., Dichter, J., Arndt-Jovin, D.J. Exp. Cell Res. (2001) [Pubmed]
  10. Genotoxic profile of inhibitors of topoisomerases I (camptothecin) and II (etoposide) in a mitotic recombination and sex-chromosome loss somatic eye assay of Drosophila melanogaster. Sortibrán, A.N., Téllez, M.G., Rodríguez-Arnaiz, R. Mutat. Res. (2006) [Pubmed]
  11. Protein kinase C phosphorylates topoisomerase II: topoisomerase activation and its possible role in phorbol ester-induced differentiation of HL-60 cells. Sahyoun, N., Wolf, M., Besterman, J., Hsieh, T., Sander, M., LeVine, H., Chang, K.J., Cuatrecasas, P. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  12. Gadd45, a p53-responsive stress protein, modifies DNA accessibility on damaged chromatin. Carrier, F., Georgel, P.T., Pourquier, P., Blake, M., Kontny, H.U., Antinore, M.J., Gariboldi, M., Myers, T.G., Weinstein, J.N., Pommier, Y., Fornace, A.J. Mol. Cell. Biol. (1999) [Pubmed]
  13. Interaction in vitro of type III intermediate filament proteins with supercoiled plasmid DNA and modulation of eukaryotic DNA topoisomerase I and II activities. Li, G., Tolstonog, G.V., Sabasch, M., Traub, P. DNA Cell Biol. (2002) [Pubmed]
  14. Cloning and characterization of the gene for the somatic form of DNA topoisomerase I from Xenopus laevis. Pandit, S.D., Richard, R.E., Sternglanz, R., Bogenhagen, D.F. Nucleic Acids Res. (1996) [Pubmed]
  15. DNA superhelicity affects the formation of transcription preinitiation complex on eukaryotic genes differently. Mizutani, M., Ura, K., Hirose, S. Nucleic Acids Res. (1991) [Pubmed]
  16. Cloning and characterization of Drosophila topoisomerase IIIbeta. Relaxation of hypernegatively supercoiled DNA. Wilson, T.M., Chen, A.D., Hsieh, T. J. Biol. Chem. (2000) [Pubmed]
  17. Structure of the Drosophila DNA topoisomerase I gene and expression of messages with different lengths in the 3' untranslated region. Brown, S.D., Zhang, C.X., Chen, A.D., Hsieh, T.S. Gene (1998) [Pubmed]
  18. A protein kinase activity tightly associated with Drosophila type II DNA topoisomerase. Sander, M., Nolan, J.M., Hsieh, T. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  19. Localization of specific topoisomerase I interactions within the transcribed region of active heat shock genes by using the inhibitor camptothecin. Gilmour, D.S., Elgin, S.C. Mol. Cell. Biol. (1987) [Pubmed]
  20. Preferential cleavage of plasmid-based R-loops and D-loops by Drosophila topoisomerase IIIbeta. Wilson-Sali, T., Hsieh, T.S. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  21. DNA topoisomerase II from Drosophila melanogaster. Relaxation of supercoiled DNA. Osheroff, N., Shelton, E.R., Brutlag, D.L. J. Biol. Chem. (1983) [Pubmed]
  22. Evidence that intergenic spacer repeats of Drosophila melanogaster rRNA genes function as X-Y pairing sites in male meiosis, and a general model for achiasmatic pairing. McKee, B.D., Habera, L., Vrana, J.A. Genetics (1992) [Pubmed]
  23. Patterns of variation in the intergenic spacers of ribosomal DNA in Drosophila melanogaster support a model for genetic exchanges during X-Y pairing. Polanco, C., González, A.I., Dover, G.A. Genetics (2000) [Pubmed]
  24. Novel HeLa topoisomerase II is the II beta isoform: complete coding sequence and homology with other type II topoisomerases. Austin, C.A., Sng, J.H., Patel, S., Fisher, L.M. Biochim. Biophys. Acta (1993) [Pubmed]
  25. The gene encoding topoisomerase I from the human malaria parasite Plasmodium falciparum. Tosh, K., Kilbey, B. Gene (1995) [Pubmed]
  26. Topoisomerase II-catalyzed ATP hydrolysis as monitored by thin-layer chromatography. Kingma, P.S., Fortune, J.M., Osheroff, N. Methods Mol. Biol. (2001) [Pubmed]
  27. Association of topoisomerase I with transcriptionally active loci in Drosophila. Gilmour, D.S., Elgin, S.C. NCI monographs : a publication of the National Cancer Institute. (1987) [Pubmed]
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