| The transcriptional response to distinct growth factors is impaired in Werner syndrome cells. | |
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MedLine Citation:
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PMID: 18625297 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The Werner syndrome protein (WRN) is mutated in Werner syndrome (WS) and plays a role in telomere maintenance, DNA repair and transcription. WS represents a premature aging syndrome with severe growth retardation. Here we show that WRN is critically required to mediate the stimulatory effect of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-b) and epidermal growth factor (EGF) on the activity of RNA polymerase I (Pol I). Recombinant WRN specifically reconstitutes RNA polymerase I transcription in extracts from Werner syndrome fibroblasts in vitro. In addition, we identified a critical role for WRN during promoter clearance of Pol I transcription, but not in elongation. Notably, WRN was isolated in a complex with Pol I and was crosslinked to the unmethylated, active proportion of rDNA genes in quiescent cells suggesting a so far unknown role for WRN in epigenetic regulation. This together with alterations in Pol I transcription provide a novel mechanism possibly underlying at least in part the severe growth retardation and premature aging in Werner syndrome patients. |
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Authors:
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Anna Lutomska; Anton Lebedev; Karin Scharffetter-Kochanek; Sebastian Iben |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-06-25 |
Journal Detail:
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Title: Experimental gerontology Volume: 43 ISSN: 1873-6815 ISO Abbreviation: Exp. Gerontol. Publication Date: 2008 Sep |
Date Detail:
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Created Date: 2008-08-25 Completed Date: 2009-04-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0047061 Medline TA: Exp Gerontol Country: England |
Other Details:
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Languages: eng Pagination: 820-6 Citation Subset: IM |
Affiliation:
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Department of Dermatology and Allergic Diseases, University of Ulm, Maienweg 12, 89081 Ulm, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cells, Cultured DNA Methylation DNA, Ribosomal / metabolism DNA-Binding Proteins / metabolism Exodeoxyribonucleases / genetics, metabolism, pharmacology Fibroblasts / drug effects, pathology Humans Intercellular Signaling Peptides and Proteins / pharmacology* Mutation Promoter Regions, Genetic RNA Polymerase I / genetics RecQ Helicases / genetics, metabolism, pharmacology Recombinant Proteins / pharmacology Transcription, Genetic / drug effects* Werner Syndrome / genetics*, metabolism, pathology |
| Chemical | |
Reg. No./Substance:
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0/DNA, Ribosomal; 0/DNA-Binding Proteins; 0/Intercellular Signaling Peptides and Proteins; 0/Recombinant Proteins; EC 2.7.7.-/RNA Polymerase I; EC 3.1.-/Exodeoxyribonucleases; EC 3.6.1.-/RecQ Helicases; EC 3.6.1.-/WRN protein, human |
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