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  • Original Paper
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A role for PML and the nuclear body in genomic stability

Oncogene volume 18, pages 7941–7947 (1999)Cite this article

Abstract

The PML gene of acute promyelocytic leukemia (APL) encodes a cell-growth and tumor suppressor. PML localizes to discrete nuclear bodies (NBs) that are disrupted in APL cells. The Bloom syndrome gene BLM encodes a RecQ DNA helicase, whose absence from the cell results in genomic instability epitomized by high levels of sister-chromatid exchange (SCE) and cancer predisposition. We show here that BLM co-localizes with PML to the NB. In cells from persons with Bloom syndrome the localization of PML is unperturbed, whereas in APL cells carrying the PML-RARα oncoprotein, both PML and BLM are delocalized from the NB into microspeckled nuclear regions. Treatment with retinoic acid (RA) induces the relocalization of both proteins to the NB. In primary PML−/− cells, BLM fails to accumulate in the NB. Strikingly, in PML−/− cells the frequency of SCEs is increased relative to PML+/+ cells. These data demonstrate that BLM is a constituent of the NB and that PML is required for its accumulation in these nuclear domains and for the normal function of BLM. Thus, our findings suggest a role for BLM in APL pathogenesis and implicate the PML NB in the maintenance of genomic stability.

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Acknowledgements

We thank Drs P Dotto, P Freemont, K Manova and M Sadelain for discussions, materials and advice in some experiments. PP Pandolfi is a Scholar of the Leukemia Society of America. Supported by the NCI (CA-08748) and NIH (CA-71692 awarded to PP Pandolfi).

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Authors and Affiliations

  1. Department of Human Genetics, Laboratory of Molecular and Developmental Biology, Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, 10021, NY, USA

    Sue Zhong & Pier Paolo Pandolfi

  2. Department of Human Genetics, Laboratory of Cancer Susceptibility, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, 10021, NY, USA

    Peng Hu, Tian-Zhang Ye, Rodica Stan & Nathan A Ellis

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Zhong, S., Hu, P., Ye, TZ. et al. A role for PML and the nuclear body in genomic stability. Oncogene 18, 7941–7947 (1999). https://doi.org/10.1038/sj.onc.1203367

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