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DNA Topoisomerases pp 1–9Cite as

Introduction: Emerging Themes in DNA Topoisomerase Research

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Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 582))

Abstract

DNA topoisomerases are enzymes that alter the topology of DNA. They have important functions in DNA replication, transcription, Holliday junction dissolution, chromosome condensation, and sister chromatid separation. Deficiencies in these enzymes are associated with diseases that result from genome instability. The last 10–15 years has seen a great deal of exciting research in the field of topoisomerase. Here we discuss a selection of the new themes that have been recently introduced into the already large body of topoisomerase research.

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References

  1. Cook, P. R. (1991) The nucleoskeleton and the topology of replication. Cell 66, 627–35.

    Article  PubMed  CAS  Google Scholar 

  2. Champoux, J. J. (1978) Proteins that affect DNA conformation. Annu Rev Biochem 47, 449–79.

    Article  PubMed  CAS  Google Scholar 

  3. Liu, L. F., Liu, C. C. and Alberts, B. M. (1979) T4 DNA topoisomerase: a new ATP-dependent enzyme essential for initiation of T4 bacteriophage DNA replication. Nature 281, 456–61.

    Article  PubMed  CAS  Google Scholar 

  4. Brown, P. O. and Cozzarelli, N. R. (1979) A sign inversion mechanism for enzymatic supercoiling of DNA. Science 206, 1081–3.

    Article  PubMed  CAS  Google Scholar 

  5. Baxter, J. and Diffley, J. F. (2008) Topoisomerase II inactivation prevents the completion of DNA replication in budding yeast. Mol Cell 30, 790–802.

    Article  PubMed  CAS  Google Scholar 

  6. Clarke, D. J., Vas, A. C., Andrews, C. A., Diaz-Martinez, L. A. and Gimenez-Abian, J. F. (2006) Topoisomerase II checkpoints: universal mechanisms that regulate mitosis. Cell Cycle 5, 1925–8.

    Article  PubMed  CAS  Google Scholar 

  7. Skoufias, D. A., Lacroix, F. B., Andreassen, P. R., Wilson, L. and Margolis, R. L. (2004) Inhibition of DNA decatenation, but not DNA damage, arrests cells at metaphase. Mol Cell 15, 977–90.

    Article  PubMed  CAS  Google Scholar 

  8. Damelin, M., Sun, Y. E., Sodja, V. B. and Bestor, T. H. (2005) Decatenation checkpoint deficiency in stem and progenitor cells. Cancer Cell 8, 479–84.

    Article  PubMed  CAS  Google Scholar 

  9. Doherty, S. C., McKeown, S. R., McKelvey-Martin, V., Downes, C. S., Atala, A., Yoo, J. J., Simpson, D. A. and Kaufmann, W. K. (2003) Cell cycle checkpoint function in bladder cancer. J Natl Cancer Inst 95, 1859–68.

    Article  PubMed  CAS  Google Scholar 

  10. Nakagawa, T., Hayashita, Y., Maeno, K., Masuda, A., Sugito, N., Osada, H., Yanagisawa, K., Ebi, H., Shimokata, K. and Takahashi, T. (2004) Identification of decatenation G2 checkpoint impairment independently of DNA damage G2 checkpoint in human lung cancer cell lines. Cancer Res 64, 4826–32.

    Article  PubMed  CAS  Google Scholar 

  11. Andrews, C. A., Vas, A. C., Meier, B., Gimenez-Abian, J. F., Diaz-Martinez, L. A., Green, J., Erickson, S. L., Vanderwaal, K. E., Hsu, W. S. and Clarke, D. J. (2006) A mitotic topoisomerase II checkpoint in budding yeast is required for genome stability but acts independently of Pds1/securing. Genes Dev 20, 1162–74.

    Article  PubMed  CAS  Google Scholar 

  12. Newport, J. and Spann, T. (1987) Disassembly of the nucleus in mitotic extracts: membrane vesicularization, lamin disassembly, and chromosome condensation are independent processes. Cell 48, 219–30.

    Article  PubMed  CAS  Google Scholar 

  13. Uemura, T., Ohkura, H., Adachi, Y., Morino, K., Shiozaki, K. and Yanagida, M. (1987) DNA topoisomerase II is required for condensation and separation of mitotic chromosomes in S. pombe. Cell 50, 917–25.

    Article  PubMed  CAS  Google Scholar 

  14. Wood, E. R. and Earnshaw, W. C. (1990) Mitotic chromatin condensation in vitro using somatic cell extracts and nuclei with variable levels of endogenous topoisomerase II. J Cell Biol 111, 2839–50.

    Article  PubMed  CAS  Google Scholar 

  15. Adachi, Y., Luke, M. and Laemmli, U. K. (1991) Chromosome assembly in vitro: topoisomerase II is required for condensation. Cell 64, 137–48.

    Article  PubMed  CAS  Google Scholar 

  16. Giménez-Abián, J. F., Clarke, D. J., Devlin, J., Giménez-Abián, M., De la Torre, C., Johnson, R. T., Mullinger, A. M. and Downes, C. S. (2000) Premitotic chromosome individualization in mammalian cells depends on topoisomerase II activity. Chromosoma 109, 235–44.

    Article  PubMed  Google Scholar 

  17. Agostinho, M., Santos, V., Ferreira, F., Costa, R., Cardoso, J., Pinheiro, I., Rino, J., Jaffray, E., Hay, R. T. and Ferreira, J. (2008) Conjugation of human topoisomerase 2 alpha with small ubiquitin-like modifiers 2/3 in response to topoisomerase inhibitors: cell cycle stage and chromosome domain specificity. Cancer Res 68, 2409–18.

    Article  PubMed  CAS  Google Scholar 

  18. Azuma, Y., Arnaoutov, A., Anan, T. and Dasso, M. (2005) PIASy mediates SUMO-2 conjugation of Topoisomerase-II on mitotic chromosomes. EMBO J 24, 2172–82.

    Article  PubMed  CAS  Google Scholar 

  19. Azuma, Y., Arnaoutov, A. and Dasso, M. (2003) SUMO-2/3 regulates topoisomerase II in mitosis. J Cell Biol 163, 477–87.

    Article  PubMed  CAS  Google Scholar 

  20. Bachant, J., Alcasabas, A., Blat, Y., Kleckner, N. and Elledge, S. J. (2002) The SUMO-1 isopeptidase Smt4 is linked to centromeric cohesion through SUMO-1 modification of DNA topoisomerase II. Mol Cell 9, 1169–82.

    Article  PubMed  CAS  Google Scholar 

  21. Diaz-Martinez, L. A., Gimenez-Abian, J. F., Azuma, Y., Guacci, V., Gimenez-Martin, G., Lanier, L. M. and Clarke, D. J. (2006) PIASgamma is required for faithful chromosome segregation in human cells. PLoS ONE 1, e53.

    Article  PubMed  Google Scholar 

  22. Takahashi, Y., Yong-Gonzalez, V., Kikuchi, Y. and Strunnikov, A. (2006) SIZ1/SIZ2 control of chromosome transmission fidelity is mediated by the sumoylation of topoisomerase II. Genetics 172, 783–94.

    Article  PubMed  CAS  Google Scholar 

  23. Dawlaty, M. M., Malureanu, L., Jeganathan, K. B., Kao, E., Sustmann, C., Tahk, S., Shuai, K., Grosschedl, R. and van Deursen, J. M. (2008) Resolution of sister centromeres requires RanBP2-mediated SUMOylation of topoisomerase IIalpha. Cell 133, 103–15.

    Article  PubMed  CAS  Google Scholar 

  24. Carpenter, A. J. and Porter, A. C. (2004) Construction, characterization, and complementation of a conditional-lethal DNA topoisomerase IIalpha mutant human cell line. Mol Biol Cell 15, 5700–11.

    Article  PubMed  CAS  Google Scholar 

  25. Wang, J. C. (2002) Cellular roles of DNA topoisomerases: a molecular perspective. Nat Rev Mol Cell Biol 3, 430–40.

    Article  PubMed  CAS  Google Scholar 

  26. Zhu, Q., Pongpech, P. and DiGate, R. J. (2001) Type I topoisomerase activity is required for proper chromosomal segregation in Escherichia coli. Proc Natl Acad Sci USA 98, 9766–71.

    Article  PubMed  CAS  Google Scholar 

  27. Masse, E. and Drolet, M. (1999) Relaxation of transcription-induced negative supercoiling is an essential function of Escherichia coli DNA topoisomerase I. J Biol Chem 274, 16654–8.

    Article  PubMed  CAS  Google Scholar 

  28. Kirkegaard, K. and Wang, J. C. (1985) Bacterial DNA topoisomerase I can relax positively supercoiled DNA containing a single-stranded loop. J Mol Biol 185, 625–37.

    Article  PubMed  CAS  Google Scholar 

  29. Champoux, J. J. (2001) DNA topoisomerases: structure, function, and mechanism. Annu Rev Biochem 70, 369–413.

    Article  PubMed  CAS  Google Scholar 

  30. Lopez, C. R., Yang, S., Deibler, R. W., Ray, S. A., Pennington, J. M., Digate, R. J., Hastings, P. J., Rosenberg, S. M. and Zechiedrich, E. L. (2005) A role for topoisomerase III in a recombination pathway alternative to RuvABC. Mol Microbiol 58, 80–101.

    Article  PubMed  CAS  Google Scholar 

  31. del Toro Duany, Y., Jungblut, S. P., Schmidt, A. S. and Klostermeier, D. (2008) The reverse gyrase helicase-like domain is a nucleotide-dependent switch that is attenuated by the topoisomerase domain. Nucleic Acids Res 36, 5882–95.

    Article  PubMed  CAS  Google Scholar 

  32. Taneja, B., Schnurr, B., Slesarev, A., Marko, J. F. and Mondragon, A. (2007) Topoisomerase V relaxes supercoiled DNA by a constrained swiveling mechanism. Proc Natl Acad Sci USA 104, 14670–5.

    Article  PubMed  CAS  Google Scholar 

  33. Belova, G. I., Prasad, R., Kozyavkin, S. A., Lake, J. A., Wilson, S. H. and Slesarev, A. I. (2001) A type IB topoisomerase with DNA repair activities. Proc Natl Acad Sci USA 98, 6015–20.

    Article  PubMed  CAS  Google Scholar 

  34. Snoep, J. L., van der Weijden, C. C., Andersen, H. W., Westerhoff, H. V. and Jensen, P. R. (2002) DNA supercoiling in Escherichia coli is under tight and subtle homeostatic control, involving gene-expression and metabolic regulation of both topoisomerase I and DNA gyrase. Eur J Biochem 269, 1662–9.

    Article  PubMed  CAS  Google Scholar 

  35. Menzel, R. and Gellert, M. (1983) Regulation of the genes for E. coli DNA gyrase: homeostatic control of DNA supercoiling. Cell 34, 105–13.

    Article  PubMed  CAS  Google Scholar 

  36. Wang, X., Reyes-Lamothe, R. and Sherratt, D. J. (2008) Modulation of Escherichia coli sister chromosome cohesion by topoisomerase IV. Genes Dev 22, 2426–33.

    Article  PubMed  CAS  Google Scholar 

  37. Zechiedrich, E. L., Khodursky, A. B. and Cozzarelli, N. R. (1997) Topoisomerase IV, not gyrase, decatenates products of site-specific recombination in Escherichia coli. Genes Dev 11, 2580–92.

    Article  PubMed  CAS  Google Scholar 

  38. Nichols, M. D., DeAngelis, K., Keck, J. L. and Berger, J. M. (1999) Structure and function of an archaeal topoisomerase VI subunit with homology to the meiotic recombination factor Spo11. Embo J 18, 6177–88.

    Article  PubMed  CAS  Google Scholar 

  39. Wallis, J. W., Chrebet, G., Brodsky, G., Rolfe, M. and Rothstein, R. (1989) A hyper-recombination mutation in S. cerevisiae identifies a novel eukaryotic topoisomerase. Cell 58, 409–19.

    Article  PubMed  CAS  Google Scholar 

  40. Kim, R. A. and Wang, J. C. (1992) Identification of the yeast TOP3 gene product as a single strand-specific DNA topoisomerase. J Biol Chem 267, 17178–85.

    PubMed  CAS  Google Scholar 

  41. Megonigal, M. D., Fertala, J. and Bjornsti, M. A. (1997) Alterations in the catalytic activity of yeast DNA topoisomerase I result in cell cycle arrest and cell death. J Biol Chem 272, 12801–8.

    Article  PubMed  CAS  Google Scholar 

  42. Garinther, W. I. and Schultz, M. C. (1997) Topoisomerase function during replication-independent chromatin assembly in yeast. Mol Cell Biol 17, 3520–6.

    PubMed  CAS  Google Scholar 

  43. DiNardo, S., Voelkel, K. and Sternglanz, R. (1984) 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 USA 81, 2616–20.

    Article  PubMed  CAS  Google Scholar 

  44. Hanai, R., Caron, P. R. and Wang, J. C. (1996) Human TOP3: a single-copy gene encoding DNA topoisomerase III. Proc Natl Acad Sci USA 93, 3653–7.

    Article  PubMed  CAS  Google Scholar 

  45. Ng, S. W., Liu, Y., Hasselblatt, K. T., Mok, S. C. and Berkowitz, R. S. (1999) A new human topoisomerase III that interacts with SGS1 protein. Nucleic Acids Res 27, 993–1000.

    Article  PubMed  CAS  Google Scholar 

  46. Gimenez-Abian, J. F., Clarke, D. J., Gimenez-Martin, G., Weingartner, M., Gimenez-Abian, M. I., Carballo, J. A., Diaz, D., Bogre, L. and De, L. (2002) DNA catenations that link sister chromatids until the onset of anaphase are maintained by a checkpoint mechanism. Eur J Cell Biol 81, 9–16.

    Article  PubMed  CAS  Google Scholar 

  47. Warburton, P. E. and Earnshaw, W. C. (1997) Untangling the role of DNA topoisomerase II in mitotic chromosome structure and function. Bioessays 19, 97–9.

    Article  PubMed  CAS  Google Scholar 

  48. Bauman, M. E., Holden, J. A., Brown, K. A., Harker, W. G. and Perkins, S. L. (1997) Differential immunohistochemical staining for DNA topoisomerase II alpha and beta in human tissues and for DNA topoisomerase II beta in non-Hodgkin’s lymphomas. Mod Pathol 10, 168–75.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department Genetics, Cell Biology & Development, University of Minnesota, Medical School, Minneapolis, MN, USA

    Duncan J. Clarke & Andrew Lane

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  1. Duncan J. Clarke
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  2. Andrew Lane
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Editors and Affiliations

  1. Dept. Genetics, Cell Biology &, University of Minnesota Medical School, Washington Ave. SE. 420, Minneapolis, 55455, U.S.A.

    Duncan J. Clarke

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC

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Clarke, D.J., Lane, A. (2009). Introduction: Emerging Themes in DNA Topoisomerase Research. In: Clarke, D. (eds) DNA Topoisomerases. Methods in Molecular Biology™, vol 582. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-340-4_1

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  • DOI: https://doi.org/10.1007/978-1-60761-340-4_1

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  • Publisher Name: Humana Press, Totowa, NJ

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