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The role of CSA in the response to oxidative DNA damage in human cells

Oncogene volume 26, pages 4336–4343 (2007)Cite this article

Abstract

Cockayne syndrome (CS) is a rare genetic disease characterized by severe growth, mental retardation and pronounced cachexia. CS is most frequently due to mutations in either of two genes, CSB and CSA. Evidence for a role of CSB protein in the repair of oxidative DNA damage has been provided recently. Here, we show that CSA is also involved in the response to oxidative stress. CS-A human primary fibroblasts and keratinocytes showed hypersensitivity to potassium bromate, a specific inducer of oxidative damage. This was associated with inefficient repair of oxidatively induced DNA lesions, namely 8-hydroxyguanine (8-OH-Gua) and (5′S)-8,5′-cyclo 2′-deoxyadenosine. Expression of the wild-type CSA in the CS-A cell line CS3BE significantly decreased the steady-state level of 8-OH-Gua and increased its repair rate following oxidant treatment. CS-A cell extracts showed normal 8-OH-Gua cleavage activity in an in vitro assay, whereas CS-B cell extracts were confirmed to be defective. Our data provide the first in vivo evidence that CSA protein contributes to prevent accumulation of various oxidized DNA bases and underline specific functions of CSB not shared with CSA. These findings support the hypothesis that defective repair of oxidative DNA damage is involved in the clinical features of CS patients.

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Acknowledgements

Grant support: Associazione Italiana per la Ricerca sul Cancro (AIRC), Compagnia di S Paolo (Programma Oncologia) to GF, MIUR/FIRB (RBNE01RNN7, RBIN042YJ7) and Fondazione Cariplo. Certain commercial equipment or materials are identified in this paper to specify adequately the experimental procedure. Such identification does not imply recommendation or endorsement by the National Institute of Standards and Technology, nor does it imply that the materials or equipment identified are necessarily the best available for the purpose.

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Author notes

  1. E Parlanti, M Teson and P Degan: These two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena, Rome, Italy

    M D'Errico, E Parlanti, T Lemma, A Calcagnile, I Iavarone & E Dogliotti

  2. Laboratory of Molecular and Cell Biology, Istituto Dermopatico dell'Immacolata, IRCCS, Via Monti di Creta, Rome, Italy

    M Teson & G Zambruno

  3. Department of Translational Oncology, Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi, Genova, Italy

    P Degan, M Ropolo & G Frosina

  4. Department Chemical and Biochemical Engineering, University of Maryland Baltimore County, Baltimore, MD, USA

    P Jaruga

  5. Chemical Science and Technology Laboratory, National Institute of Standards and Technology, Gaithersburg, MD, USA

    P Jaruga & M Dizdaroglu

  6. Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, Via Abbiategrasso, Pavia, Italy

    A M Pedrini, D Orioli & M Stefanini

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  1. M D'Errico
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  2. E Parlanti
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  3. M Teson
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  8. P Jaruga
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Correspondence to E Dogliotti.

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D'Errico, M., Parlanti, E., Teson, M. et al. The role of CSA in the response to oxidative DNA damage in human cells. Oncogene 26, 4336–4343 (2007). https://doi.org/10.1038/sj.onc.1210232

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  • DOI: https://doi.org/10.1038/sj.onc.1210232

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