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Screening for Radiation Sensitizers of Drosophila Checkpoint Mutants

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Book cover Cell Cycle Checkpoints

Part of the book series: Methods in Molecular Biology ((MIMB,volume 782))

Abstract

Anti-cancer therapy is largely comprised of radiation, surgery, and chemotherapy treatments. Although a single mode of therapy can be effective in treating certain types of cancer, none presents a cure. Multi-modal therapy, the use of two or more agents in combination (e.g., radiation and chemotherapy together), shows potential for a more effective treatment of cancer. The challenge then is identifying effective therapy combinations. In this chapter, we describe the use of Drosophila as a whole animal in vivo model to screen for small molecules that effectively combine with ionizing radiation to kill checkpoint mutants preferentially over wild-type. The differential use of wild-type and checkpoint mutants has the potential to identify molecules that act in a genotype-specific manner to eradicate checkpoint mutant tissues when combined with radiation, while sparing wild-type tissues.

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References

  1. Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., and Walter, P. (2002) Molecular Biology of the Cell, Fourth ed., Garland, New York.

    Google Scholar 

  2. Ma, B. B., Bristow, R. G., Kim, J., and Siu, L. L. (2003) Combined-modality treatment of solid tumors using radiotherapy and molecular targeted agents, J Clin Oncol 21, 2760–2776.

    Article  PubMed  CAS  Google Scholar 

  3. Parchment, R. E., Gordon, M., Grieshaber, C. K., Sessa, C., Volpe, D., and Ghielmini, M. (1998) Predicting hematological toxicity (myelosuppression) of cytotoxic drug therapy from in vitro tests, Ann Oncol 9, 357–364.

    Article  PubMed  CAS  Google Scholar 

  4. Smith, R. S., Chen, Q., Hudson, M. M., Link, M. P., Kun, L., Weinstein, H., Billett, A., Marcus, K. J., Tarbell, N. J., and Donaldson, S. S. (2003) Prognostic factors for children with Hodgkin’s disease treated with combined-modality therapy, J Clin Oncol 21, 2026–2033.

    Article  PubMed  Google Scholar 

  5. David, H. L. (1970) Probability distribution of drug-resistant mutants in unselected populations of Mycobacterium tuberculosis, Appl Microbiol 20, 810–814.

    PubMed  CAS  Google Scholar 

  6. Sharma, P. L., Nurpeisov, V., Hernandez-Santiago, B., Beltran, T., and Schinazi, R. F. (2004) Nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase, Curr Top Med Chem 4, 895–919.

    Article  PubMed  CAS  Google Scholar 

  7. Jaklevic, B., Uyetake, L., Lemstra, W., Chang, J., Leary, W., Edwards, A., Vidwans, S., Sibon, O., and Tin Su, T. (2006) Contribution of growth and cell cycle checkpoints to radiation survival in Drosophila, Genetics 174, 1963–1972.

    Article  PubMed  CAS  Google Scholar 

  8. Jaklevic, B. R., and Su, T. T. (2004) Relative contribution of DNA repair, cell cycle checkpoints, and cell death to survival after DNA damage in Drosophila larvae, Curr Biol 14, 23–32.

    Article  PubMed  CAS  Google Scholar 

  9. Fogarty, P., Kalpin, R. F., and Sullivan, W. (1994) The Drosophila maternal-effect mutation grapes causes a metaphase arrest at nuclear cycle 13, Development 120, 2131–2142.

    PubMed  CAS  Google Scholar 

  10. Fogarty, P., Campbell, S. D., Abu-Shumays, R., Phalle, B. S., Yu, K. R., Uy, G. L., Goldberg, M. L., and Sullivan, W. (1997) The Drosophila grapes gene is related to checkpoint gene chk1/rad27 and is required for late syncytial division fidelity, Curr Biol 7, 418–426.

    Article  PubMed  CAS  Google Scholar 

  11. Purdy, A., Uyetake, L., Cordeiro, M. G., and Su, T. T. (2005) Regulation of mitosis in response to damaged or incompletely replicated DNA require different levels of Grapes (Drosophila Chk1), J Cell Sci 118, 3305–3315.

    Article  PubMed  CAS  Google Scholar 

  12. Rong, Y. S., Titen, S. W., Xie, H. B., Golic, M. M., Bastiani, M., Bandyopadhyay, P., Olivera, B. M., Brodsky, M., Rubin, G. M., and Golic, K. G. (2002) Targeted mutagenesis by homologous recombination in D. melanogaster, Genes Dev 16, 1568–1581.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors thank Petros Yoon for critical reading of the manuscript and for his contribution to the screen. The work in the Su lab is supported by an NIH grant (GM087276) to T. T. Su.

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Correspondence to Tin Tin Su .

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© 2011 Springer Science+Business Media, LLC

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Gladstone, M., Su, T.T. (2011). Screening for Radiation Sensitizers of Drosophila Checkpoint Mutants. In: Li, W. (eds) Cell Cycle Checkpoints. Methods in Molecular Biology, vol 782. Humana Press. https://doi.org/10.1007/978-1-61779-273-1_9

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  • DOI: https://doi.org/10.1007/978-1-61779-273-1_9

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-272-4

  • Online ISBN: 978-1-61779-273-1

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