Document Detail

The transcriptional response to distinct growth factors is impaired in Werner syndrome cells.
MedLine Citation:
PMID:  18625297     Owner:  NLM     Status:  MEDLINE    
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.
Anna Lutomska; Anton Lebedev; Karin Scharffetter-Kochanek; Sebastian Iben
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-06-25
Journal Detail:
Title:  Experimental gerontology     Volume:  43     ISSN:  1873-6815     ISO Abbreviation:  Exp. Gerontol.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-25     Completed Date:  2009-04-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0047061     Medline TA:  Exp Gerontol     Country:  England    
Other Details:
Languages:  eng     Pagination:  820-6     Citation Subset:  IM    
Department of Dermatology and Allergic Diseases, University of Ulm, Maienweg 12, 89081 Ulm, Germany.
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MeSH Terms
Cells, Cultured
DNA Methylation
DNA, Ribosomal / metabolism
DNA-Binding Proteins / metabolism
Exodeoxyribonucleases / genetics,  metabolism,  pharmacology
Fibroblasts / drug effects,  pathology
Intercellular Signaling Peptides and Proteins / pharmacology*
Promoter Regions, Genetic
RNA Polymerase I / genetics
RecQ Helicases / genetics,  metabolism,  pharmacology
Recombinant Proteins / pharmacology
Transcription, Genetic / drug effects*
Werner Syndrome / genetics*,  metabolism,  pathology
Reg. No./Substance:
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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