title: Werner syndrome: Clinical features, pathogenesis and potential therapeutic interventions.
abstract: Werner syndrome (WS) is a prototypical segmental progeroid syndrome characterized by multiple features consistent with accelerated aging. It is caused by null mutations of the WRN gene, which encodes a member of the RECQ family of DNA helicases. A unique feature of the WRN helicase is the presence of an exonuclease domain in its N-terminal region. Biochemical and cell biological studies during the past decade have demonstrated involvements of the WRN protein in multiple DNA transactions, including DNA repair, recombination, replication and transcription. A role of the WRN protein in telomere maintenance could explain many of the WS phenotypes. Recent discoveries of new progeroid loci found in atypical Werner cases continue to support the concept of genomic instability as a major mechanism of biological aging. Based on these biological insights, efforts are underway to develop therapeutic interventions for WS and related progeroid syndromes.
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA 98195, USA; Department of Medicine, Chiba University, Chiba, Japan. Electronic address: picard@u.washington.edu.
authors.forename: Junko
authors.initials: J
authors.lastname: Oshima
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Sidorova
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA 98195, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Monnat
mesh_terms: D019588:Aging, Premature / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004261:DNA Replication; D005090:Exodeoxyribonucleases; D006801:Humans; D009154:Mutation; D014898:Werner Syndrome / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000071657:Werner Syndrome Helicase / Q000235:genetics*
chemical_list: D005090:Exodeoxyribonucleases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase
keywords: Genomic instability; Human; Progeroid syndrome; Werner syndrome