A role for PML and the nuclear body in genomic stability
| Autor: | Sue Zhong, Peng Hu, Tian-Zhang Ye, Nathan A. Ellis, Pier Paolo Pandolfi, Rodica Stan |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Keratinocytes
Genome instability Acute promyelocytic leukemia congenital hereditary and neonatal diseases and abnormalities Cancer Research Tumor suppressor gene viruses HL-60 Cells Tretinoin Promyelocytic Leukemia Protein Biology Transfection Cell Line Mice Promyelocytic leukemia protein Leukemia Promyelocytic Acute Genetics medicine Animals Humans Bloom syndrome Nuclear protein Fluorescent Antibody Technique Indirect Molecular Biology Adenosine Triphosphatases Cell Nucleus RecQ Helicases urogenital system Tumor Suppressor Proteins Homozygote DNA Helicases Nuclear Proteins virus diseases nutritional and metabolic diseases U937 Cells medicine.disease Neoplasm Proteins Cell biology Cell nucleus medicine.anatomical_structure Codon Terminator biology.protein Sister Chromatid Exchange Bloom Syndrome HeLa Cells Transcription Factors |
| Zdroj: | Oncogene. 18:7941-7947 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1203367 |
| Popis: | 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-RARalpha 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. |
| Databáze: | OpenAIRE |
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