Formaldehyde catabolism is essential in cells deficient for the Fanconi anemia DNA-repair pathway (original) (raw)

Nature Structural & Molecular Biology volume 18, pages 1432–1434 (2011)Cite this article

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Abstract

Metabolism is predicted to generate formaldehyde, a toxic, simple, reactive aldehyde that can damage DNA. Here we report a synthetic lethal interaction in avian cells between ADH5, encoding the main formaldehyde-detoxifying enzyme, and the Fanconi anemia (FA) DNA-repair pathway. These results define a fundamental role for the combined action of formaldehyde catabolism and DNA cross-link repair in vertebrate cell survival.

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Figure 1: The FA DNA-repair pathway ensures genome stability after exogenous formaldehyde exposure.

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Figure 2: FANCD2 and ADH5 are synthetically lethal in DT40 cells.

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Figure 3: The FA core complex gene FANCL and ADH5 are synthetically lethal in DT40 cells.

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References

  1. Muller, L.U. & Williams, D.A. Mutat. Res. 668, 141–149 (2009).
    Article PubMed PubMed Central Google Scholar
  2. Crossan, G.P. et al. Nat. Genet. 43, 147–152 (2011).
    Article CAS PubMed PubMed Central Google Scholar
  3. Stoepker, C. et al. Nat. Genet. 43, 138–141 (2011).
    Article CAS PubMed Google Scholar
  4. Kim, Y. et al. Nat. Genet. 43, 142–146 (2011).
    Article CAS PubMed PubMed Central Google Scholar
  5. Joenje, H. & Patel, K.J. Nat. Rev. Genet. 2, 446–457 (2001).
    Article CAS PubMed Google Scholar
  6. Patel, K.J. & Joenje, H. DNA Repair (Amst.) 6, 885–890 (2007).
    Article CAS Google Scholar
  7. de Winter, J.P. & Joenje, H. Mutat. Res. 668, 11–19 (2009).
    Article CAS PubMed Google Scholar
  8. Rosado, I.V., Niedzwiedz, W., Alpi, A.F. & Patel, K.J. Nucleic Acids Res. 37, 4360–4370 (2009).
    Article CAS PubMed PubMed Central Google Scholar
  9. Langevin, F., Crossan, G.P., Rosado, I.V., Arends, M.J. & Patel, K.J. Nature 475, 53–58 (2011).
    Article CAS PubMed Google Scholar
  10. Mosammaparast, N. & Shi, Y. Annu. Rev. Biochem. 79, 155–179 (2010).
    Article CAS PubMed Google Scholar
  11. Ridpath, J.R. et al. Cancer Res. 67, 11117–11122 (2007).
    Article CAS PubMed Google Scholar
  12. Noda, T. et al. Biochem. Biophys. Res. Commun. 404, 206–210 (2011).
    Article CAS PubMed Google Scholar
  13. Nomura, Y., Adachi, N. & Koyama, H. Genes Cells 12, 1111–1122 (2007).
    Article CAS PubMed Google Scholar
  14. Trewick, S.C., Henshaw, T.F., Hausinger, R.P., Lindahl, T. & Sedgwick, B. Nature 419, 174–178 (2002).
    Article CAS PubMed Google Scholar
  15. Falnes, P.O., Johansen, R.F. & Seeberg, E. Nature 419, 178–182 (2002).
    Article CAS PubMed Google Scholar
  16. Iborra, F.J. et al. J. Histochem. Cytochem. 40, 1865–1878 (1992).
    Article CAS PubMed Google Scholar
  17. Mosedale, G. et al. Nat. Struct. Mol. Biol. 12, 763–771 (2005).
    Article CAS PubMed Google Scholar
  18. Zhang, X.Y. et al. PLoS Genet. 5, e1000645 (2009).
    Article PubMed PubMed Central Google Scholar

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Acknowledgements

We thank N. Adachi and H. Koyama (Kihara Institute for Biological Research, Japan) for kindly providing NALM-6 human cell lines. We are grateful to J. Sutherland and K. Lang (MRC Laboratory of Molecular Biology) for chemical insight and to M. Daly and F. Zhang (MRC Laboratory of Molecular Biology) for invaluable help with flow cytometry. I.V.R. and F.L. are funded by the Fanconi Anaemia Research Fund and Children's Leukaemia Trust, respectively.

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Authors and Affiliations

  1. Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Ivan V Rosado, Frédéric Langevin, Gerry P Crossan & Ketan J Patel
  2. Department of Late Effect Studies, Laboratory of DNA Damage Signaling, Radiation Biology Center, Kyoto University, Kyoto, Japan
    Minoru Takata
  3. Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
    Ketan J Patel

Authors

  1. Ivan V Rosado
  2. Frédéric Langevin
  3. Gerry P Crossan
  4. Minoru Takata
  5. Ketan J Patel

Contributions

I.V.R. and K.J.P. designed the study and the experiments, and wrote the paper. I.V.R. performed the majority of the experiments presented. F.L. contributed to DT40 clonogenic assays and assisted in the generation of _ADH5_-deficient cell lines. G.P.C. helped with analysis of chromosome breaks. M.T. generated and provided the FANCD2 inducible cell line.

Corresponding author

Correspondence toKetan J Patel.

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The authors declare no competing financial interests.

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Rosado, I., Langevin, F., Crossan, G. et al. Formaldehyde catabolism is essential in cells deficient for the Fanconi anemia DNA-repair pathway.Nat Struct Mol Biol 18, 1432–1434 (2011). https://doi.org/10.1038/nsmb.2173

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