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PML NBs associate with the hMre11 complex and p53 at sites of irradiation induced DNA damage

Oncogene volume 21, pages 1633–1640 (2002)Cite this article

Abstract

PML nuclear bodies (PML NBs) respond to many cellular stresses including viral infection, heat shock, arsenic and oncogenes and have been implicated in the regulation of p53-dependent replicative senescence and apoptosis. Recently, the hMre11/Rad50/NBS1 repair complex, involved in Double Strand Breaks (DSBs) repair, was found to colocalize within PML NBs, suggesting a role for these nuclear sub-domains in the DNA repair signalling pathway. We report here that in normal human fibroblasts, after ionizing radiation (IR), the PML NBs are modified and recognize sites of DNA breaks (ssDNA breaks and DSBs). Eight to 12 h after radiation PML NBs associate with hMre11 Ionizing Radiation-Induced Foci (IRIF), and subsequently with p53 within discrete foci. The PML, hMre11 and p53 colocalizing structures mark sites of DSBs as identified by immunolocalization with anti phosphorylated histone γ-H2AX. Furthermore, we demonstrate that ionizing radiation induces the stable association of p53 with hMre11 and PML. These results suggest that the PML NBs are involved in the recognition and/or processing of DNA breaks and possibly in the recruitment of proteins (p53 and hMre11) required for both checkpoint and DNA-repair responses.

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Acknowledgements

We thank Pietro Transidico for technical assistance in confocal analysis and the Service of Medical Physics of our Institute for technical help. This work was supported by grants from AIRC and the EC.

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Authors and Affiliations

  1. Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, Milan, 20141, Italy

    Roberta Carbone, Mark Pearson, Saverio Minucci & Pier Giuseppe Pelicci

  2. FIMO, FIRC Institute for Molecular Oncology, Via Serio 21, Milan, 20139, Italy

    Pier Giuseppe Pelicci

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  1. Roberta Carbone
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  2. Mark Pearson
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  3. Saverio Minucci
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  4. Pier Giuseppe Pelicci
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Correspondence to Pier Giuseppe Pelicci.

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Carbone, R., Pearson, M., Minucci, S. et al. PML NBs associate with the hMre11 complex and p53 at sites of irradiation induced DNA damage. Oncogene 21, 1633–1640 (2002). https://doi.org/10.1038/sj.onc.1205227

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