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Proteasome-dependent dispersal of PML nuclear bodies in response to alkylating DNA damage

Oncogene volume 23, pages 307–310 (2004)Cite this article

Abstract

Promyelocytic leukemia protein (PML) nuclear bodies (NBs) are present in variable number in most human cell types and have been linked to various cellular functions, including roles as depots for DNA repair proteins. Here, we show that treatment of human cells with DNA methylating agents leads to redistribution of PML from NBs to a diffuse nuclear localization. Biochemically, this correlates with a specific reduction of PML levels in the nuclear matrix fraction without affecting total PML levels. Similar results were obtained for the other major PML NB component, the Sp100 protein, indicating that DNA methylating agents lead to a general disassembly of PML NBs. Similar to the dispersal of PML NBs in response to some viral infections, PML redistribution after DNA damage was inhibited by the proteasome inhibitor MG132. We propose that the regulated dispersal of PML NBs may facilitate the enhanced release of DNA repair proteins from NB depots in order to respond adequately to extensive DNA damage.

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Acknowledgements

We thank Virginia Leopold for tissue culture support and David Thomas for cell lines. This work was supported by grants from the National Health and Medical Research Council of Australia (NHMRC) and the Cancer Council Victoria to JH, and an Australian Postgraduate Award (to CJM).

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Authors and Affiliations

  1. St Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, 3065, Victoria, Australia

    Lindus A Conlan, Carolyn J McNees & Jörg Heierhorst

  2. Department of Medicine, St Vincent's Hospital, The University of Melbourne, Fitzroy, 3065, Victoria, Australia

    Carolyn J McNees & Jörg Heierhorst

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  1. Lindus A Conlan
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Correspondence to Jörg Heierhorst.

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Conlan, L., McNees, C. & Heierhorst, J. Proteasome-dependent dispersal of PML nuclear bodies in response to alkylating DNA damage. Oncogene 23, 307–310 (2004). https://doi.org/10.1038/sj.onc.1207119

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