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. 1994 Jul 11;22(13):2547–2551. doi: 10.1093/nar/22.13.2547

The gene encoding topoisomerase II from Plasmodium falciparum.

S Cheesman 1, S McAleese 1, M Goman 1, D Johnson 1, P Horrocks 1, R G Ridley 1, B J Kilbey 1
PMCID: PMC308208  PMID: 8041616

Abstract

The gene for topoisomerase II has been isolated from genomic libraries of strain K1 of the human malarial parasite, Plasmodium falciparum. The sequence reveals an open reading frame of 4194 nucleotides which predicts a polypeptide of 1398 amino acids. There are apparently no introns. The sequence is present as a single copy which has an identity of 47.4% and a similarity of 65.4% with its human homologue. Sequences conserved in topoisomerase II from other species are present in Pftopoisomerase II but in addition it has two adjacent asparagine-rich insertions which are unique to it. We have also detected asparagine-rich regions in the gene for PfDNA polymerase alpha. The gene for Pftopoisomerase II has been localised to chromosome 14 and northern analysis reveals a transcript of 5.8 kb. Two independent antisera raised in mice against glutathione-S-transferase fusion proteins containing the amino terminal portion of the malarial protein detect a weak band on western blots at about 160kDa, the expected size of the protein. Use of the same antisera for immunofluorescence analysis suggests that the protein is present at all stages of intraerythrocytic growth of the parasite.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adachi Y., Luke M., Laemmli U. K. Chromosome assembly in vitro: topoisomerase II is required for condensation. Cell. 1991 Jan 11;64(1):137–148. doi: 10.1016/0092-8674(91)90215-k. [DOI] [PubMed] [Google Scholar]
  2. Cardenas M. E., Dang Q., Glover C. V., Gasser S. M. Casein kinase II phosphorylates the eukaryote-specific C-terminal domain of topoisomerase II in vivo. EMBO J. 1992 May;11(5):1785–1796. doi: 10.1002/j.1460-2075.1992.tb05230.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cardenas M. E., Gasser S. M. Regulation of topoisomerase II by phosphorylation: a role for casein kinase II. J Cell Sci. 1993 Feb;104(Pt 2):219–225. doi: 10.1242/jcs.104.2.219. [DOI] [PubMed] [Google Scholar]
  4. Chavalitshewinkoon P., Wilairat P., Gamage S., Denny W., Figgitt D., Ralph R. Structure-activity relationships and modes of action of 9-anilinoacridines against chloroquine-resistant Plasmodium falciparum in vitro. Antimicrob Agents Chemother. 1993 Mar;37(3):403–406. doi: 10.1128/aac.37.3.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  6. Delves C. J., Alano P., Ridley R. G., Goman M., Holloway S. P., Hyde J. E., Scaife J. G. Expression of alpha and beta tubulin genes during the asexual and sexual blood stages of Plasmodium falciparum. Mol Biochem Parasitol. 1990 Dec;43(2):271–278. doi: 10.1016/0166-6851(90)90151-b. [DOI] [PubMed] [Google Scholar]
  7. Delves C. J., Ridley R. G., Goman M., Holloway S. P., Hyde J. E., Scaife J. G. Cloning of a beta-tubulin gene from Plasmodium falciparum. Mol Microbiol. 1989 Nov;3(11):1511–1519. doi: 10.1111/j.1365-2958.1989.tb00137.x. [DOI] [PubMed] [Google Scholar]
  8. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DiNardo S., Voelkel K., Sternglanz R. DNA topoisomerase II mutant of Saccharomyces cerevisiae: topoisomerase II is required for segregation of daughter molecules at the termination of DNA replication. Proc Natl Acad Sci U S A. 1984 May;81(9):2616–2620. doi: 10.1073/pnas.81.9.2616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Earnshaw W. C., Halligan B., Cooke C. A., Heck M. M., Liu L. F. Topoisomerase II is a structural component of mitotic chromosome scaffolds. J Cell Biol. 1985 May;100(5):1706–1715. doi: 10.1083/jcb.100.5.1706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fairman R., Brutlag D. L. Expression of the Drosophila type II topoisomerase is developmentally regulated. Biochemistry. 1988 Jan 26;27(2):560–565. doi: 10.1021/bi00402a009. [DOI] [PubMed] [Google Scholar]
  12. Fu S., Xiao S. H. Pyronaridine: A new antimalarial drug. Parasitol Today. 1991 Nov;7(11):310–313. doi: 10.1016/0169-4758(91)90267-r. [DOI] [PubMed] [Google Scholar]
  13. Gasser S. M., Laemmli U. K. Cohabitation of scaffold binding regions with upstream/enhancer elements of three developmentally regulated genes of D. melanogaster. Cell. 1986 Aug 15;46(4):521–530. doi: 10.1016/0092-8674(86)90877-9. [DOI] [PubMed] [Google Scholar]
  14. Gasser S. M., Laroche T., Falquet J., Boy de la Tour E., Laemmli U. K. Metaphase chromosome structure. Involvement of topoisomerase II. J Mol Biol. 1986 Apr 20;188(4):613–629. doi: 10.1016/s0022-2836(86)80010-9. [DOI] [PubMed] [Google Scholar]
  15. Giaever G., Lynn R., Goto T., Wang J. C. The complete nucleotide sequence of the structural gene TOP2 of yeast DNA topoisomerase II. J Biol Chem. 1986 Sep 25;261(27):12448–12454. [PubMed] [Google Scholar]
  16. Goman M., Langsley G., Hyde J. E., Yankovsky N. K., Zolg J. W., Scaife J. G. The establishment of genomic DNA libraries for the human malaria parasite Plasmodium falciparum and identification of individual clones by hybridisation. Mol Biochem Parasitol. 1982 Jun;5(6):391–400. doi: 10.1016/0166-6851(82)90012-3. [DOI] [PubMed] [Google Scholar]
  17. Goman M., Mons B., Scaife J. The complete sequence of a Plasmodium malariae SSUrRNA gene and its comparison to other plasmodial SSUrRNA genes. Mol Biochem Parasitol. 1991 Apr;45(2):281–288. doi: 10.1016/0166-6851(91)90096-o. [DOI] [PubMed] [Google Scholar]
  18. Heck M. M., Hittelman W. N., Earnshaw W. C. Differential expression of DNA topoisomerases I and II during the eukaryotic cell cycle. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1086–1090. doi: 10.1073/pnas.85.4.1086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Holm C., Goto T., Wang J. C., Botstein D. DNA topoisomerase II is required at the time of mitosis in yeast. Cell. 1985 Jun;41(2):553–563. doi: 10.1016/s0092-8674(85)80028-3. [DOI] [PubMed] [Google Scholar]
  20. Hwang J. L., Shyy S. H., Chen A. Y., Juan C. C., Whang-Peng J. Studies of topoisomerase-specific antitumor drugs in human lymphocytes using rabbit antisera against recombinant human topoisomerase II polypeptide. Cancer Res. 1989 Feb 15;49(4):958–962. [PubMed] [Google Scholar]
  21. Kilbey B. J., Fraser I., McAleese S., Goman M., Ridley R. G. Molecular characterisation and stage-specific expression of proliferating cell nuclear antigen (PCNA) from the malarial parasite, Plasmodium falciparum. Nucleic Acids Res. 1993 Jan 25;21(2):239–243. doi: 10.1093/nar/21.2.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Klein F., Laroche T., Cardenas M. E., Hofmann J. F., Schweizer D., Gasser S. M. Localization of RAP1 and topoisomerase II in nuclei and meiotic chromosomes of yeast. J Cell Biol. 1992 Jun;117(5):935–948. doi: 10.1083/jcb.117.5.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lambros C., Vanderberg J. P. Synchronization of Plasmodium falciparum erythrocytic stages in culture. J Parasitol. 1979 Jun;65(3):418–420. [PubMed] [Google Scholar]
  24. Li W. B., Bzik D. J., Horii T., Inselburg J. Structure and expression of the Plasmodium falciparum SERA gene. Mol Biochem Parasitol. 1989 Feb;33(1):13–25. doi: 10.1016/0166-6851(89)90037-6. [DOI] [PubMed] [Google Scholar]
  25. Lindsley J. E., Wang J. C. Proteolysis patterns of epitopically labeled yeast DNA topoisomerase II suggest an allosteric transition in the enzyme induced by ATP binding. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10485–10489. doi: 10.1073/pnas.88.23.10485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Liu L. F. DNA topoisomerase poisons as antitumor drugs. Annu Rev Biochem. 1989;58:351–375. doi: 10.1146/annurev.bi.58.070189.002031. [DOI] [PubMed] [Google Scholar]
  27. Moens P. B., Earnshaw W. C. Anti-topoisomerase II recognizes meiotic chromosome cores. Chromosoma. 1989 Nov;98(5):317–322. doi: 10.1007/BF00292383. [DOI] [PubMed] [Google Scholar]
  28. Ridley R. G. Proteins of unusual sequence composition from the malarial parasite Plasmodium falciparum. Biochem Soc Trans. 1991 Apr;19(2):525–528. doi: 10.1042/bst0190525. [DOI] [PubMed] [Google Scholar]
  29. Ridley R. G., White J. H., McAleese S. M., Goman M., Alano P., de Vries E., Kilbey B. J. DNA polymerase delta: gene sequences from Plasmodium falciparum indicate that this enzyme is more highly conserved than DNA polymerase alpha. Nucleic Acids Res. 1991 Dec 25;19(24):6731–6736. doi: 10.1093/nar/19.24.6731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Schneider E., Hsiang Y. H., Liu L. F. DNA topoisomerases as anticancer drug targets. Adv Pharmacol. 1990;21:149–183. doi: 10.1016/s1054-3589(08)60342-7. [DOI] [PubMed] [Google Scholar]
  32. Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
  33. Sullivan D. M., Glisson B. S., Hodges P. K., Smallwood-Kentro S., Ross W. E. Proliferation dependence of topoisomerase II mediated drug action. Biochemistry. 1986 Apr 22;25(8):2248–2256. doi: 10.1021/bi00356a060. [DOI] [PubMed] [Google Scholar]
  34. Thaithong S., Beale G. H. Resistance of ten Thai isolates of Plasmodium falciparum to chloroquine and pyrimethamine by in vitro tests. Trans R Soc Trop Med Hyg. 1981;75(2):271–273. doi: 10.1016/0035-9203(81)90333-3. [DOI] [PubMed] [Google Scholar]
  35. Triglia T., Wellems T. E., Kemp D. J. Towards a high-resolution map of the Plasmodium falciparum genome. Parasitol Today. 1992 Jul;8(7):225–229. doi: 10.1016/0169-4758(92)90118-l. [DOI] [PubMed] [Google Scholar]
  36. Tsai-Pflugfelder M., Liu L. F., Liu A. A., Tewey K. M., Whang-Peng J., Knutsen T., Huebner K., Croce C. M., Wang J. C. Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21-22. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7177–7181. doi: 10.1073/pnas.85.19.7177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Uemura T., Ohkura H., Adachi Y., Morino K., Shiozaki K., Yanagida M. DNA topoisomerase II is required for condensation and separation of mitotic chromosomes in S. pombe. Cell. 1987 Sep 11;50(6):917–925. doi: 10.1016/0092-8674(87)90518-6. [DOI] [PubMed] [Google Scholar]
  38. White J. H., Kilbey B. J., de Vries E., Goman M., Alano P., Cheesman S., McAleese S., Ridley R. G. The gene encoding DNA polymerase alpha from Plasmodium falciparum. Nucleic Acids Res. 1993 Aug 11;21(16):3643–3646. doi: 10.1093/nar/21.16.3643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Worland S. T., Wang J. C. Inducible overexpression, purification, and active site mapping of DNA topoisomerase II from the yeast Saccharomyces cerevisiae. J Biol Chem. 1989 Mar 15;264(8):4412–4416. [PubMed] [Google Scholar]
  40. Wyckoff E., Natalie D., Nolan J. M., Lee M., Hsieh T. Structure of the Drosophila DNA topoisomerase II gene. Nucleotide sequence and homology among topoisomerases II. J Mol Biol. 1989 Jan 5;205(1):1–13. doi: 10.1016/0022-2836(89)90361-6. [DOI] [PubMed] [Google Scholar]
  41. Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]
  42. Zolg J. W., MacLeod A. J., Dickson I. H., Scaife J. G. Plasmodium falciparum: modifications of the in vitro culture conditions improving parasitic yields. J Parasitol. 1982 Dec;68(6):1072–1080. [PubMed] [Google Scholar]

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