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Involvement of DNA replication in ultraviolet-induced apoptosis of mammalian cells

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Abstract

Exposure of cells to ultraviolet (UV) light damages the genome and the persistence of DNA lesions triggers apoptosis in mammalian cells. RNA transcription blockage by DNA damage is believed to be implicated in signaling for UV-induced apoptosis, but the role played by DNA replication in this process is still unclear. To address this point, we have employed the DNA polymerase inhibitor aphidicolin in UV-irradiated wild-type and XPB-mutated Chinese hamster ovary cells. The data obtained with synchronized cells indicate that induction of apoptosis by UV light is independent of the cell cycle phase. Nevertheless, cells treated with aphidicolin after UV exposure showed a significant prevention of apoptosis induction when compared to proliferating cells. These results were observed in both DNA-repair proficient and deficient cells, indicating that the prevention of apoptosis by aphidicolin is independent of the cells’ ability to repair the photolesions caused by UV. Taken together, these data suggest that replication of damaged DNA also leads to critical events signaling for UV-induced cell death.

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References

  1. Friedberg EC, Walker GC, Siede W (1995) DNA damage. In: Friedberg EC (ed) DNA repair and mutagenesis, vol 1. ASM Press, Washington, pp. 1–47

  2. Bender K, Blattner C, Knebel A, Iordanov M, Herlich P, Rahmsdorf HJ (1997) UV-induced signal transduction. J Photochem Photobiol 37:1–17

    Article  CAS  Google Scholar 

  3. Martin SJ, Green DR (1995) Proteases activation during apoptosis: Death induced by a thousand cuts? Cell 82:349–352

    Article  PubMed  CAS  Google Scholar 

  4. Saini KS, Walker NI (1998) Biochemical and molecular mechanisms regulating apoptosis. Mol Cell Biochem 178:9–25

    Article  PubMed  CAS  Google Scholar 

  5. Costa RM, Chiganças V, Galhardo RS, Carvalho H, Menck CFM (2003) The eukaryotic nucleotide excision repair pathway. Biochimie 85:1083–1099

    Article  PubMed  CAS  Google Scholar 

  6. Ma L, Hoeijmakers JHJ, van der Eb AJ (1995) Mammalian nucleotide excision repair. Biochim Biophys Acta 1242:137–163

    PubMed  Google Scholar 

  7. Lehmann AR (2003) DNA repair-deficient diseases, xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Biochimie 85:1101–1111

    Article  PubMed  CAS  Google Scholar 

  8. Chiganças V, Miyaji EN, Muotri AR, Jacsyn JF, Amarante-Mendes GP, Yasui A, Menck CFM (2000) Photorepair prevents ultraviolet-induced apoptosis in human cells expressing the marsupial photolyase gene. Cancer Res 60:2458–2463

    PubMed  Google Scholar 

  9. Chiganças V, Batista LFZ, Brumatti G, Amarante-Mendes GP, Yasui A, Menck CFM (2002) Photorepair of RNA polymerase arrest and apoptosis after ultraviolet irradiation in normal and XPB deficient rodent cells. Cell Death Differ 9:1099–1107

    Article  PubMed  CAS  Google Scholar 

  10. Menck CFM (2002) Shining a light on photolyases. Nat Genet 32:338–339

    Article  PubMed  CAS  Google Scholar 

  11. Li YF, Kim ST, Sancar A (1993) Evidence for lack of DNA photoreactivating enzyme in humans. Proc Natl Acad Sci USA 90:4389–4393

    Article  PubMed  CAS  Google Scholar 

  12. Thompson CL, Sancar A (2002) Photolyase/cryptochrome blue-light photoreceptors use photon energy to repair DNA and reset the circadian clock. Oncogene 21:9043–9056

    Article  PubMed  CAS  Google Scholar 

  13. Lindahl T, Satoh MS, Poirier GG, Klungland A (1995) Post-translational modification of poly(ADP-ribose)polymerase induced by DNA strand breaks. Trends Biochem Sci 20:405–411

    Article  PubMed  CAS  Google Scholar 

  14. Lehmann AR (2002) Replication of damaged DNA in mammalian cells: New solutions to an old problem. Mutat Res 509:23–34

    PubMed  CAS  Google Scholar 

  15. Friedberg EC, Wagner R, Radman M (2002) Specialized DNA polymerases, cellular survival, and the genesis of mutations. Science 296:1627–1630

    Article  PubMed  CAS  Google Scholar 

  16. Miyaji EN, Menck CFM (1995) Ultraviolet-induced cell death is independent of DNA replication in rat kangaroo cells. Photochem Photobiol 61:454–458

    PubMed  CAS  Google Scholar 

  17. McKay B, Becerril C, Spronck J, Ljungman M (2002) Ultraviolet light-induced apoptosis is associated with S-phase in primary human fibroblasts. DNA Repair (Amst) 1:811–820

    Article  CAS  Google Scholar 

  18. Dunkern TR, Kaina B (2002) Cell proliferation and DNA breaks are involved in ultraviolet light-induced apoptosis in nucleotide excision repair-deficient chinese hamster cells. Mol Biol Cell 13:348–361

    Article  PubMed  CAS  Google Scholar 

  19. Spadari S, Pedrali-Noy G, Ciomei M, Falaschi A, Ciarrocchi G (1984) Control of DNA replication and cell proliferation in eukaryotes by aphidicolin. Toxicol Pathol 12:143–148

    Article  PubMed  CAS  Google Scholar 

  20. Balajee AS, May A, Dianov GL, Friedberg EC, Bohr VA (1997) Reduced RNA polymerase II transcription in intact and permeabilized Cockayne syndrome group B cells. Proc Natl Acad Sci USA 94:4306–4311

    Article  PubMed  CAS  Google Scholar 

  21. Amarante-Mendes GP, Bossy-Wetzel E, Brunner T, Green DR (1998) Apoptosis essays. In: Spector DL, Goldman R, Leiwand L (eds) Cell: A laboratory manual, vol 15. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 3731–3737

  22. Chiganças V, Sarasin A, Menck CFM (2004) CPD-photolyase adenovirus-mediated gene transfer in normal and DNA-repair-deficient human cells. J Cell Sci 15:3579–3592

    Article  CAS  Google Scholar 

  23. Nakajima S, Lan L, Kanno et al (2004) UV light-induced DNA damage and tolerance for the survival of nucleotide excision repair-deficient human cells. J Biol Chem 279:46674–46677

    Article  PubMed  CAS  Google Scholar 

  24. Ljungman M, Lane DP (2004) Transcription—guarding the genome by sensing DNA damage. Nat Rev Cancer 4:727–737

    Article  PubMed  CAS  Google Scholar 

  25. Donahue BA, Yin S, Taylor JS, Reines D, Hanawalt PC (1994) Transcript cleavage by RNA polymerase II by a cyclobutane pyrimidine dimer in the DNA template. Proc Natl Acad Sci USA 91:8502–8506

    Article  PubMed  CAS  Google Scholar 

  26. Ljungman M, Zhang F (1996) Blockage of RNA polymerase as a possible trigger for u.v. light-induced apoptosis. Oncogene 13:823–831

    PubMed  CAS  Google Scholar 

  27. Carvalho H, Costa RMA, Chiganças et al (2003) Effect of cell confluence on ultraviolet light apoptotic responses in repair deficient cells. Mutat Res 544:159–166

    Article  PubMed  CAS  Google Scholar 

  28. Halicka HD, Huang X, Traganos F, King MA, Dai W, Darzynkiewics Z (2005) Histone H2AX phosphorylation after cell irradiation with UV-B. Cell Cycle 4:124–130

    Google Scholar 

  29. Konishi A, Shimizu S, Hirota et al (2003) Involvement of histone H1.2 in apoptosis induced by DNA double-strand breaks. Cell 114:673–688

    Article  PubMed  CAS  Google Scholar 

  30. Hammond EH, Green SL, Giaccia AJ (2003) Comparison of hypoxia-induced replication arrest with hydroxyurea and aphidicolin-induced arrest. Mutat Res 532:205–213

    PubMed  CAS  Google Scholar 

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Author notes

  1. Vanessa Chiganças

    Present address: Laboratory of Genetic Instability and Cancer, Gustave Roussy Institute, France

  2. Gabriela Brumatti

    Present address: Department of Genetics, Trinity College, Dublin, Ireland

Authors and Affiliations

  1. Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, 05508-900, SP, Brazil

    Luis Francisco Zirnberger Batista, Vanessa Chiganças & Carlos Frederico Martins Menck

  2. Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, 05508-900, SP, Brazil

    Gabriela Brumatti & Gustavo Pessini Amarante-Mendes

  3. Immunology Investigation Institute—Millennium Institutes, Brazil

    Gustavo Pessini Amarante-Mendes

  4. Depto. de Microbiologia, ICB, USP, Av. Prof. Lineu Prestes, 1374. Ed. Biomédicas 2, São Paulo, 05508-900, SP, Brazil

    Carlos Frederico Martins Menck

Authors
  1. Luis Francisco Zirnberger Batista
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  2. Vanessa Chiganças
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  3. Gabriela Brumatti
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  4. Gustavo Pessini Amarante-Mendes
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  5. Carlos Frederico Martins Menck
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Corresponding author

Correspondence to Carlos Frederico Martins Menck.

Additional information

This work was supported by FAPESP (São Paulo, Brazil), CNPq (Brasília, Brazil), CAPES (Brasilia, Brazil) and COFECUB (Aix en Provence, France). CFMM is a Fellow from the John Simon Guggenheim Memorial Foundation (New York, USA).

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Batista, L.F.Z., Chiganças, V., Brumatti, G. et al. Involvement of DNA replication in ultraviolet-induced apoptosis of mammalian cells. Apoptosis 11, 1139–1148 (2006). https://doi.org/10.1007/s10495-006-7109-4

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  • DOI: https://doi.org/10.1007/s10495-006-7109-4

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