Advertisement

Topoisomerase-Induced DNA Damage

  • Yves Pommier
  • Neil Osheroff
Chapter
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

Because of their ability to cleave and religate DNA by covalently bonding to one of the ends of the DNA break, topoisomerases are highly susceptible to DNA structure. Here, we will review how topoisomerases can damage the genome when it contains preexisting DNA lesions at the enzyme sites of action. This brief chapter gives an overview of the broad range of lesions that lead to the accumulation of cleavage complexes produced by DNA topoisomerases I and II.

Keywords

Double Helix Abasic Site Cleavage Complex Scissile Bond Suicide Substrate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Antony S, Arimondo PB, Sun JS, Pommier Y (2004a) Position- and orientation-specific enhancement of topoisomerase I cleavage complexes by triplex DNA structures. Nucleic Acids Res 32(17): 5163–5173CrossRefPubMedCentralPubMedGoogle Scholar
  2. Antony S, Theruvathu JA, Brooks PJ, Lesher DT, Redinbo M, Pommier Y (2004b) Enhancement of camptothecin-induced topoisomerase I cleavage complexes by the acetaldehyde adduct N2-ethyl-2’-deoxyguanosine. Nucleic Acids Res 32(18): 5685–5692Google Scholar
  3. Baranello L, Bertozzi D, Fogli MV, Pommier Y, Capranico G (2010) DNA topoisomerase I inhibition by camptothecin induces escape of RNA polymerase II from promoter-proximal pause site, antisense transcription and histone acetylation at the human HIF-1alpha gene locus. Nucleic Acids Res 38(1): 159–171CrossRefPubMedCentralPubMedGoogle Scholar
  4. Barnes DE, Lindahl T (2004) Repair and genetic consequences of endogenous DNA base damage in mammalian cells. Annu Rev Genet 38: 445–476CrossRefPubMedGoogle Scholar
  5. Beckman KB, Ames BN (1997) Oxidative decay of DNA. J Biol Chem 272(32): 19633–19636CrossRefPubMedGoogle Scholar
  6. Belyaev IY (2005) DNA loop organization and DNA fragmentation during radiation-induced apoptosis in human lymphocytes. Radiats Biol Radioecol 45(5): 541–548PubMedGoogle Scholar
  7. Bermejo R, Doksani Y, Capra T, Katou YM, Tanaka H, Shirahige K, Foiani M (2007) Top1- and Top2-mediated topological transitions at replication forks ensure fork progression and stability and prevent DNA damage checkpoint activation. Genes Dev 21(15): 1921–1936CrossRefPubMedCentralPubMedGoogle Scholar
  8. Berrios M, Osheroff N, Fisher PA (1985) In situ localization of DNA topoisomerase II, a major polypeptide component of the Drosophila nuclear matrix fraction. Proc Natl Acad Sci USA 82(12): 4142–4146CrossRefPubMedCentralPubMedGoogle Scholar
  9. Bigioni M, Zunino F, Capranico G (1994) Base mutation analysis of topoisomerase II-idarubicin-DNA ternary complex formation. Evidence for enzyme subunit cooperativity in DNA cleavage. Nucleic Acids Res 22(12): 2274–2281CrossRefPubMedCentralPubMedGoogle Scholar
  10. Champoux JJ, Dulbecco R (1972) An activity from mammalian cells that untwists superhelical DNA--a possible swivel for DNA replication (polyoma-ethidium bromide-mouse-embryo cells-dye binding assay). Proc Natl Acad Sci USA 69: 143–146Google Scholar
  11. Christiansen K, Westergaard O (1994) Characterization of intra- and intermolecular DNA ligation mediated by eukaryotic topoisomerase I. J Biol Chem 269: 721–729PubMedGoogle Scholar
  12. Cline SD, Osheroff N (1999) Cytosine arabinoside (araC) lesions are position-specific topoisomerase II poisons and stimulate DNA cleavage mediated by the human type II enzymes. J Biol Chem 274: 29740–29743CrossRefPubMedGoogle Scholar
  13. Corbett AH, Zechiedrich EL, Lloyd RS, Osheroff N (1991) Inhibition of eukaryotic topoisomerase II by ultraviolet-induced cyclobutane pyrimidine dimers. J Biol Chem 266(29): 19666–19671PubMedGoogle Scholar
  14. Deweese JE, Burgin AB, Osheroff N (2008) Using 3’-bridging phosphorothiolates to isolate the forward DNA cleavage reaction of human topoisomerase IIalpha. Biochemistry 47(13): 4129–4140Google Scholar
  15. Deweese JE, Osheroff N (2009a) Coordinating the two protomer active sites of human topoisomerase IIalpha: nicks as topoisomerase II poisons. Biochemistry 48(7): 1439–1441CrossRefPubMedCentralPubMedGoogle Scholar
  16. Deweese JE, Osheroff N (2009b) The DNA cleavage reaction of topoisomerase II: wolf in sheep’s clothing. Nucleic Acids Res 37(3): 738–748Google Scholar
  17. Dexheimer TS, Antony S, Marchand C, Pommier Y (2008a) Tyrosyl-DNA phosphodiesterase as a target for anticancer therapy. Anticancer Agents Med Chem 8(4): 381–389CrossRefPubMedCentralPubMedGoogle Scholar
  18. Dexheimer TS, Kozekova A, Rizzo CJ, Stone MP, Pommier Y (2008b) The modulation of topoisomerase I-mediated DNA cleavage and the induction of DNA-topoisomerase I crosslinks by crotonaldehyde-derived DNA adducts. Nucleic Acids Res 36(12): 4128–4136CrossRefPubMedCentralPubMedGoogle Scholar
  19. Dong KC, Berger JM (2007) Structural basis for gate-DNA recognition and bending by type IIA topoisomerases. Nature 450(7173): 1201–1205CrossRefPubMedGoogle Scholar
  20. Earnshaw WC, Heck MM (1985) Localization of topoisomerase II in mitotic chromosomes. J Cell Biol 100(5): 1716–1725CrossRefPubMedGoogle Scholar
  21. Hardin AH, Sarkar SK, Seol Y, Liou GF, Osheroff N, Neuman KC (2011) Direct measurement of DNA bending by type IIA topoisomerases: implications for non-equilibrium topology simplification. Nucleic Acids Res Google Scholar
  22. Henningfeld KA, Arslan T, Hecht SM (1996) Alteration of DNA primary structure by topoisomerase I. Isolation of the covalent topoisomerase I-DNA binary complex in enzymatically competent form. J Am Chem Soc 47: 11701–11714CrossRefGoogle Scholar
  23. Henningfeld KA, Hecht S (1995) A model for topoisomerase I-mediated insertions and deletions with duplex DNA substrates containing branches, nicks, and gaps. Biochemistry 34: 6120–6129CrossRefPubMedGoogle Scholar
  24. Khan QA, Kohlhagen G, Marshall R, Austin CA, Kalena GP, Kroth H, Sayer JM, Jerina DM, Pommier Y (2003) Position-specific trapping of topoisomerase II by benzo[a]pyrene diol epoxide adducts: implications for interactions with intercalating anticancer agents. Proc Natl Acad Sci USA 100(21): 12498–12503CrossRefPubMedCentralPubMedGoogle Scholar
  25. Kingma PS, Burden DA, Osheroff N (1999) Binding of etoposide to topoisomerase II in the absence of DNA: decreased affinity as a mechanism of drug resistance. Biochemistry 38: 3457–3461CrossRefPubMedGoogle Scholar
  26. Kingma PS, Corbett AH, Burcham PC, Marnett LJ, Osheroff N (1995) Abasic sites stimulate double-stranded DNA cleavage mediated by topoisomerase II: anticancer drugs mimic endogenous DNA lesions. J Biol Chem 270: 21441–21444CrossRefPubMedGoogle Scholar
  27. Kingma PS, Greider CA, Osheroff N (1997) Spontaneous DNA lesions poison human topoisomerase IIα and stimulate cleavage proximal to leukemic 11q23 chromosomal breakpoints. Biochemistry 36: 5934–5939CrossRefPubMedGoogle Scholar
  28. Kingma PS, Osheroff N (1997a) Apurinic sites are position-specific topoisomerase II poisons. J Biol Chem 272(2): 1148–1155CrossRefPubMedGoogle Scholar
  29. Kingma PS, Osheroff N (1997b) Spontaneous DNA damage stimulates topoisomerase II-mediated DNA cleavage. J Biol Chem 272(11): 7488–7493CrossRefPubMedGoogle Scholar
  30. Kingma PS, Osheroff N (1998) The response of eukaryotic topoisomerases to DNA damage. Biochim Biophys Acta 1400: 223–232CrossRefPubMedGoogle Scholar
  31. Koster DA, Croquette V, Dekker C, Shuman S, Dekker NH (2005) Friction and torque govern the relaxation of DNA supercoils by eukaryotic topoisomerase IB. Nature 434(7033): 671–674CrossRefPubMedGoogle Scholar
  32. Lanza A, Tornatelli S, Rodolfo C, Scanavini MC, Pedrini AM (1996) Human DNA topoisomerase I-mediated cleavages stimulated by ultraviolet light-induced DNA damage. J Biol Chem 271: 6978–6986CrossRefPubMedGoogle Scholar
  33. Lesher DT, Pommier Y, Stewart L, Redinbo MR (2002) 8-Oxoguanine rearranges the active site of human topoisomerase I. Proc Natl Acad Sci USA 99(19): 12102–12107CrossRefPubMedCentralPubMedGoogle Scholar
  34. Leteurtre F, Kohlhagen G, Fesen MR, Tanizawa A, Kohn KW, Pommier Y (1994) Effects of DNA methylation on topoisomerase I and II cleavage activities. J Biol Chem 269: 7893–7900PubMedGoogle Scholar
  35. Lindahl T (1993) Instability and decay of the primary structure of DNA. Nature 362: 709–715CrossRefPubMedGoogle Scholar
  36. Pommier Y, Barcelo JM, Rao VA, Sordet O, Jobson AG, Thibaut L, Miao ZH, Seiler JA, Zhang H, Marchand C, Agama K, Nitiss JL, Redon C (2006) Repair of topoisomerase I-mediated DNA damage. Prog Nucleic Acid Res Mol Biol 81: 179–229CrossRefPubMedCentralPubMedGoogle Scholar
  37. Pommier Y, Jenkins J, Kohlhagen G, Leteurtre F (1995) DNA recombinase activity of eukaryotic DNA topoisomerase I; effects of camptothecin and other inhibitors. Mutat Res 337(2): 135–145CrossRefPubMedGoogle Scholar
  38. Pommier Y, Kohlhagen G, Laco GS, Kroth H, Sayer JM, Jerina DM (2002) Different effects on human topoisomerase I by minor groove and intercalated deoxyguanosine adducts derived from two polycyclic aromatic hydrocarbon diol epoxides at or near a normal cleavage site. J Biol Chem 277(16): 13666–13672CrossRefPubMedGoogle Scholar
  39. Pommier Y, Kohlhagen G, Pourquier P, Sayer JM, Kroth H, Jerina DM (2000a) Benzo[a]pyrene epoxide adducts in DNA are potent inhibitors of a normal topoisomerase I cleavage site and powerful inducers of other topoisomerase I cleavages. Proc Natl Acad Sci USA 97: 2040–2045CrossRefPubMedCentralPubMedGoogle Scholar
  40. Pommier Y, Laco GS, Kohlhagen G, Sayer JM, Kroth H, Jerina DM (2000b) Position-specific trapping of topoisomerase I-DNA cleavage complexes by intercalated benzo[a]- pyrene diol epoxide adducts at the 6-amino group of adenine. Proc Natl Acad Sci USA 97(20): 10739–10744CrossRefPubMedCentralPubMedGoogle Scholar
  41. Pommier Y, Poddevin B, Gupta M, Jenkins J (1994) DNA topoisomerases I & II cleavage sites in the type 1 human immunodeficiency virus (HIV-1) DNA promoter region. Biochem Biophys Res Commun 205(3): 1601–1609CrossRefPubMedGoogle Scholar
  42. Porter SE, Champoux JJ (1989) Mapping in vivo topoisomerase I sites on simian virus 40 DNA: asymmetric distribution of sites on replicating molecules. Mol Cell Biol 9(2): 541–550PubMedCentralPubMedGoogle Scholar
  43. Pouliot JJ, Yao KC, Robertson CA, Nash HA (1999) Yeast gene for a Tyr-DNA phosphodiesterase that repairs topo I covalent complexes. Science 286: 552–555CrossRefPubMedGoogle Scholar
  44. Pourquier P, Bjornsti M-A, Pommier Y (1998) Induction of topoisomerase I cleavage complexes by the vinyl chloride adduct, 1,N6-ethenoadenine. J Biol Chem 273: 27245–27249Google Scholar
  45. Pourquier P, Jensen AD, Gong SS, Pommier Y, Rogler CE (1999) Human DNA topoisomerase I-mediated cleavage and recombination of duck hepatitis B virus DNA in vitro. Nucleic Acids Res 27(8): 1919–1925CrossRefPubMedCentralPubMedGoogle Scholar
  46. Pourquier P, Pilon A, Kohlhagen G, Mazumder A, Sharma A, Pommier Y (1997a) Trapping of mammalian topoisomerase I and recombinations induced by damaged DNA containing nicks or gaps: importance of DNA end phosphorylation and camptothecin effects. J Biol Chem 272: 26441–26447CrossRefPubMedGoogle Scholar
  47. Pourquier P, Pommier Y (2001) Topoisomerase I-mediated DNA damage. Adv Cancer Res 80: 189–216CrossRefPubMedGoogle Scholar
  48. Pourquier P, Ueng L-M, Kohlhagen G, Mazumder A, Gupta M, Kohn KW, Pommier Y (1997b) Effects of uracil incorporation, DNA mismatches, and abasic sites on cleavage and religation activities of mammalian topoisomerase I. J Biol Chem 272: 7792–7796CrossRefPubMedGoogle Scholar
  49. Pourquier P, Waltman JL, Urasaki Y, Loktionova NA, Pegg AE, Nitiss JL, Pommier Y (2001) Topoisomerase I-mediated cytotoxicity of N-methyl-N’-nitro-N- nitrosoguanidine: trapping of topoisomerase I by the O6-methylguanine. Cancer Res 61(1): 53–58Google Scholar
  50. Sabourin M, Osheroff N (2000) Sensitivity of human type II topoisomerases to DNA damage: stimulation of enzyme-mediated DNA cleavage by abasic, oxidized and alkylated lesions. Nucleic Acids Res 28(9): 1947–1954CrossRefPubMedCentralPubMedGoogle Scholar
  51. Schmidt BH, Burgin AB, Deweese JE, Osheroff N, Berger JM (2010) A novel and unified two-metal mechanism for DNA cleavage by type II and IA topoisomerases. Nature 465(7298): 641–644CrossRefPubMedCentralPubMedGoogle Scholar
  52. Shuman S (1989) Vaccinia DNA topoisomerase I promotes illegitimate recombination in Eschrichia coli. Proceedings of the National Academy of Sciences, USA 86: 3489–3493CrossRefGoogle Scholar
  53. Solovyan VT, Bezvenyuk ZA, Salminen A, Austin CA, Courtney MJ (2002) The role of topoisomerase II in the excision of DNA loop domains during apoptosis. J Biol Chem 277(24): 21458–21467CrossRefPubMedGoogle Scholar
  54. Sordet O, Khan Q, Kohn KW, Pommier Y (2003) Apoptosis induced by topoisomerase inhibitors. Curr Med Chem Anticancer Agents 3: 271–290CrossRefPubMedGoogle Scholar
  55. Sordet O, Khan QA, Plo I, Pourquier P, Urasaki Y, Yoshida A, Antony S, Kohlhagen G, Solary E, Saparbaev M, Laval J, Pommier Y (2004a) Apoptotic Topoisomerase I-DNA Complexes Induced by Staurosporine-mediated Oxygen Radicals. J Biol Chem 279(48): 50499–50504CrossRefPubMedGoogle Scholar
  56. Sordet O, Khan QA, Pommier Y (2004b) Apoptotic Topoisomerase I-DNA Complexes Induced by Oxygen Radicals and Mitochondrial Dysfunction. Cell Cycle 3(9): 1095–1097CrossRefPubMedGoogle Scholar
  57. Sordet O, Liao Z, Liu H, Antony S, Stevens EV, Kohlhagen G, Fu H, Pommier Y (2004c) Topoisomerase I-DNA complexes contribute to arsenic trioxide-induced apoptosis. J Biol Chem 279(32): 33968–33975CrossRefPubMedGoogle Scholar
  58. Stewart L, Redinbo MR, Qiu X, Hol WG, Champoux JJ (1998) A model for the mechanism of human topoisomerase I. Science 279(5356): 1534–1541CrossRefPubMedGoogle Scholar
  59. Subramanian D, Rosenstein BS, Muller MT (1998) Ultraviolet-induced DNA damage stimulates topoisomerase I-DNA complex formation in vivo: possible relationship with DNA repair. Cancer Res 58: 976–984PubMedGoogle Scholar
  60. Velez-Cruz R, Riggins JN, Daniels JS, Cai H, Guengerich FP, Marnett LJ, Osheroff N (2005) Exocyclic DNA lesions stimulate DNA cleavage mediated by human topoisomerase II alpha in vitro and in cultured cells. Biochemistry 44(10): 3972–3981CrossRefPubMedGoogle Scholar
  61. Vilenchik MM, Knudson AG (2003) Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer. Proc Natl Acad Sci USA 100(22): 12871–12876CrossRefPubMedCentralPubMedGoogle Scholar
  62. Wang X, Henningfeld KA, Hecht SM (1998) DNA topoisomerase I-mediated formation of structurally modified DNA duplexes. Effects of metal ions and topoisomerase I inhibitors. Biochemistry 37(8): 2691–2700CrossRefPubMedGoogle Scholar
  63. Wang Y, Knudsen BR, Bjergbaek L, Westergaard O, Andersen AH (1999) Stimulated activity of human topoisomerases IIalpha and IIbeta on RNA-containing substrates. J Biol Chem 274(32): 22839–22846CrossRefPubMedGoogle Scholar
  64. Wang Y, Thyssen A, Westergaard O, Andersen AH (2000) Position-specific effect of ribonucleotides on the cleavage activity of human topoisomerase II. Nucleic Acids Res 28(24): 4815–4821CrossRefPubMedCentralPubMedGoogle Scholar
  65. Wilstermann AM, Osheroff N (2001) Base excision repair intermediates as topoisomerase II poisons. J Biol Chem 276(49): 46290–46296CrossRefPubMedGoogle Scholar
  66. Yang S-W, Burgin AB, Huizenga BN, Robertson CA, Yao KC, Nash HA (1996) A eukaryotic enzyme that can disjoin dead-end covalent complexes between DNA and type I topoisomerases. Proc Natl Acad Sci USA 93: 11534–11539CrossRefPubMedCentralPubMedGoogle Scholar
  67. Yeh Y-C, Liu H-F, Ellis CA, Lu A-L (1994) Mammalian topoisomerase I has a mismatch nicking activity. J Biol Chem 269: 15498–15504PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Laboratory of Molecular Pharmacology, Center for Cancer ResearchNational Cancer Institute, National Institutes of HealthBethesdaUSA
  2. 2.Departments of Biochemistry and Medicine (Hematology/Oncology), School of MedicineVanderbilt UniversityNashvilleUSA

Personalised recommendations