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Formaldehyde catabolism is essential in cells deficient for the Fanconi anemia DNA-repair pathway

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.
Figure 2: FANCD2 and ADH5 are synthetically lethal in DT40 cells.
Figure 3: The FA core complex gene FANCL and ADH5 are synthetically lethal in DT40 cells.

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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
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  2. Frédéric Langevin
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  4. Minoru Takata
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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.

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Correspondence to Ketan 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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