title: The Werner syndrome protein is a DNA helicase.
abstract: Werner syndrome (WS) is an uncommon autosomal recessive disorder characterized by premature aging. The clinical manifestations of WS, including atherosclerosis and osteoporosis, appear early in adulthood, and death in the fourth to sixth decade commonly ensues from myocardial infarction or cancer. In accord with the aging phenotype, cells from WS patients have a reduced replicative life span in culture. Genomic instability is observed at the cytogenetic level in the form of chromosome breaks and translocations and at the molecular level by multiple large deletions. The Werner syndrome gene (WRN) has recently been cloned. The predicted product is a 1,432-amino-acid protein whose central domain is homologous to members of the RecQ family of DNA helicases. Such homology does not necessarily mean that WRN encodes an active helicase. For example, the Saccharomyces cerevisiae RAD26 gene protein and the human transcription-repair coupling factor CSB (Cockayne syndrome 8) are highly homologous to known helicases, yet neither encodes an active helicase. Moreover, the Bloom's syndrome gene (BLM), discovered before WRN, is also homologous to the RecQ family of DNA helicases, though we still await demonstration that it encodes an active helicase. Here we report that the WS protein does indeed catalyze DNA unwinding.
authors.affiliation: Department of Pathology, University of Washington, Seattle 98195-7705, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Gray
authors.forename: J C
authors.initials: JC
authors.lastname: Shen
authors.forename: A S
authors.initials: AS
authors.lastname: Kamath-Loeb
authors.forename: A
authors.initials: A
authors.lastname: Blank
authors.forename: B L
authors.initials: BL
authors.lastname: Sopher
authors.forename: G M
authors.initials: GM
authors.lastname: Martin
authors.forename: J
authors.initials: J
authors.lastname: Oshima
authors.forename: L A
authors.initials: LA
authors.lastname: Loeb
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D017124:Conserved Sequence; D004265:DNA Helicases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D017354:Point Mutation; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D018411:Spodoptera; D014162:Transfection; D014898:Werner Syndrome / Q000201:enzymology* / Q000235:genetics*
chemical_list: D011994:Recombinant Proteins; D004265:DNA Helicases