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The Werner syndrome protein is required for recruitment of chromatin assembly factor 1 following DNA damage

Oncogene volume 26, pages 3811–3822 (2007)Cite this article

Abstract

The Werner syndrome protein (WRN) and chromatin assembly factor 1 (CAF-1) are both involved in the maintenance of genome stability. In response to DNA-damaging signals, both of these proteins relocate to sites where DNA synthesis occurs. However, the interaction between WRN and CAF-1 has not yet been investigated. In this report, we show that WRN interacts physically with the largest subunit of CAF-1, hp150, in vitro and in vivo. Although hp150 does not alter WRN catalytic activities in vitro, and the chromatin assembly activity of CAF-1 is not affected in the absence of WRN in vivo, this interaction may have an important role during the cellular response to DNA replication fork blockage and/or DNA damage signals. In hp150 RNA-mediated interference (RNAi) knockdown cells, WRN partially formed foci following hydroxyurea (HU) treatment. However, in the absence of WRN, hp150 did not relocate to form foci following exposure to HU and ultraviolet light. Thus, our results demonstrate that WRN responds to DNA damage before CAF-1 and suggest that WRN may recruit CAF-1, via interaction with hp150, to DNA damage sites during DNA synthesis.

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Acknowledgements

We thank Oleg Georgiev and Walter Schaffner for HeLa S100 extracts, Genevieve Almouzni for chromatin assembly reagents and anti-hp150 antibodies, Steve Matson for UvrD protein, and Grant Brown and Dieter Egli for comments on the manuscript. RJ is supported in part by the NSFC (Grant 30370791 and 30428029) and 973 program (2005CB522804). ISt group is financed by grants from the Canadian Government, Canadian Institute for Health Research (CIHR), Genome Canada, Novartis, Union Bank of Switzerland, Gebert Rüf Foundation, and the Swiss Cancer League (OCS-01310-02-2003).

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  1. J A Harrigan

    Present address: The Wellcome Trust/CRUK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, UK

Authors and Affiliations

  1. National Laboratory of Biomacromolecules and State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, The Chinese Academy of Sciences, Beijing, China

    R Jiao

  2. Laboratory of Molecular Gerontology, NIA, National Institutes of Health, Baltimore, MD, USA

    J A Harrigan, J Piotrowski & V A Bohr

  3. Department of Biochemistry and Department of Medical Genetics and Microbiology, Terrence Donnelly Centre for Cellular and Biomolecular Research (dCCBR), University of Toronto, Toronto, Ontario, Canada

    I Shevelev, T Dietschy & I Stagljar

  4. Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland

    N Selak

  5. Research Resources Branch, NIA, National Institutes of Health, Baltimore, MD, USA

    F E Indig

  6. Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland

    P Janscak

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Jiao, R., Harrigan, J., Shevelev, I. et al. The Werner syndrome protein is required for recruitment of chromatin assembly factor 1 following DNA damage. Oncogene 26, 3811–3822 (2007). https://doi.org/10.1038/sj.onc.1210150

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