A role for PML and the nuclear body in genomic stability Journal Article
| Authors: | Zhong, S.; Peng, H.; Ye, T. Z.; Stan, R.; Ellis, N. A.; Pandolfi, P. P. |
| Article Title: | A role for PML and the nuclear body in genomic stability |
| Abstract: | The PML gene of acute promyelocytic leukemia (APL) encodes a cell-growth and tumour 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 colocalizes 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 NE. 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. |
| Keywords: | controlled study; oncoprotein; human cell; animals; mice; cancer susceptibility; cell growth; neoplasm proteins; cell line; hela cells; transfection; transcription factors; nuclear proteins; tumor suppressor gene; leukemia, promyelocytic, acute; tumor suppressor proteins; acute myeloblastic leukemia; homozygote; sister chromatid exchange; cell nucleus; helicase; keratinocytes; adenosine triphosphatases; retinoic acid; dna helicases; fluorescent antibody technique, indirect; codon, terminator; u937 cells; tretinoin; pml; apl; hl-60 cells; cell nucleus inclusion body; sister-chromatid exchange; blm; bloom syndrome; nuclear body; humans; human; priority journal; article |
| Journal Title: | Oncogene |
| Volume: | 18 |
| Issue: | 56 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1999-12-23 |
| Start Page: | 7941 |
| End Page: | 7947 |
| Language: | English |
| PUBMED: | 10637504 |
| PROVIDER: | scopus |
| DOI: | 10.1038/sj.onc.1203367 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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