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UV-C-induced DNA damage leads to p53-dependent nuclear trafficking of PML

Oncogene volume 22, pages 1620–1628 (2003)Cite this article

Abstract

The promyelocytic leukemia protein (PML) is a nuclear phosphoprotein that localizes to distinct domains in the nucleus, described as PML nuclear bodies (PML-NBs). Recent findings indicate that PML regulates the p53 response to oncogenic signals. Here, we define a p53-dependent role for PML in response to DNA damage. We exposed cells to ultraviolet light (UV-C) and imaged the nuclear distribution of PML, p53, and the BLM helicase by confocal microscopy. After DNA damage, PML partially relocated out of the PML-NBs, and colocalized with BLM and p53 at sites of DNA repair. In addition, using the isogenic HCT116 cell lines (p53+/+ and −/−), we show that the redistribution of PML was dependent on functional p53. Western analysis revealed that the level of PML protein remained unaltered after UV-C treatment. These results are consistent with the hypothesis that PML, in conjunction with p53 and BLM, contributes to the cellular response to UV-C-induced DNA damage and its repair.

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Acknowledgements

We thank Dorothea Dudek for editorial, Judith A Welsh for graphical, and Karen MacPherson for bibliographic assistance. HS was supported, in part, by a DFG Fellowship, award no. SE 978/11.

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Author notes

  1. Hasan Seker and Carlos Rubbi: These authors contributed equally to this work

Authors and Affiliations

  1. Laboratory of Human Carcinogenesis, CCR, National Cancer Institute, NIH, Bethesda, 20892-4255, MD, USA

    Hasan Seker, Steven P Linke, Elise D Bowman & Curtis C Harris

  2. Biology Department, YCR p53 Laboratory, University of York, York, YO1 5DD, UK

    Carlos Rubbi & Jo Milner

  3. Laboratory of Experimental Carcinogenesis, CCR, National Cancer Institute, NIH, Bethesda, 20892, MD, USA

    Susan Garfield

  4. Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, 68178, NE, USA

    Laura Hansen

  5. Department of Physiology and Biophysics, Structural Biology Program, Mt Sinai School of Medicine, New York, 10029, NY, USA

    Katherine LB Borden

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  1. Hasan Seker
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Correspondence to Curtis C Harris.

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Seker, H., Rubbi, C., Linke, S. et al. UV-C-induced DNA damage leads to p53-dependent nuclear trafficking of PML. Oncogene 22, 1620–1628 (2003). https://doi.org/10.1038/sj.onc.1206140

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