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Redundancy of DNA helicases in p53-mediated apoptosis

Oncogene volume 25, pages 2119–2123 (2006)Cite this article

Abstract

A subset of DNA helicases, the RecQ family, has been found to be associated with the p53-mediated apoptotic pathway and is involved in maintaining genomic integrity. This family contains the BLM and WRN helicases, in which germline mutations are responsible for Bloom and Werner syndromes, respectively. TFIIH DNA helicases, XPB and XPD, are also components in this apoptotic pathway. We hypothesized that there may be some redundancy between helicases in their ability to complement the attenuated p53-mediated apoptotic levels seen in cells from individuals with diseases associated with these defective helicase genes. The attenuated apoptotic phenotype in Bloom syndrome cells was rescued not only by ectopic expression of BLM, but also by WRN or XPB, both 3′ → 5′ helicases, but not expression of the 5′ → 3′ helicase XPD. Overexpression of Sgs1, a WRN/BLM yeast homolog, corrected the reduction in BS cells only, which is consistent with Sgs1 being evolutionarily most homologous to BLM. A restoration of apoptotic levels in cells from WS, XPB or XPD patients was attained only by overexpression of the specific helicase. Our data suggest a limited redundancy in the pathways of these RecQ helicases in p53-induced apoptosis.

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Acknowledgements

We thank Dorothea Dudek for editorial assistance and Karen MacPherson for bibliographic assistance. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

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Authors and Affiliations

  1. Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    E A Spillare, X W Wang & C C Harris

  2. Laboratory of Molecular Gerontology, National Institute of Aging, National Institutes of Health, DHHS, Baltimore, MD, USA

    C von Kobbe & V A Bohr

  3. John Radcliffe Hospital, Cancer Research UK, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK

    I D Hickson

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  1. E A Spillare
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  2. X W Wang
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Correspondence to C C Harris.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc)

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Spillare, E., Wang, X., von Kobbe, C. et al. Redundancy of DNA helicases in p53-mediated apoptosis. Oncogene 25, 2119–2123 (2006). https://doi.org/10.1038/sj.onc.1209242

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