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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 cancer1,2. In accord with the aging phenotype, cells from WS patients have a reduced replicative life span in culture3. Genomic instability is observed at the cytogenetic level in the form of chromosome breaks and translations4 and at the molecular level by multiple large deletions5. The Werner syndrome gene (WRN) has recently been cloned6. 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 protein7 and the human transcription-repair coupling factor CSB (Cockayne syndrome B)8 are highly homologous to known helicases, yet neither encodes an active helicase. Moreover, the Bloom's syndrome gene (BLM)9, 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.

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Correspondence to Lawrence A. Loeb.

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Gray, M., Shen, JC., Kamath-Loeb, A. et al. The Werner syndrome protein is a DNA helicase. Nat Genet 17, 100–103 (1997). https://doi.org/10.1038/ng0997-100

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