THE WERNER-SYNDROME PROTEIN IS A DNA HELICASE

Werner syndrome (WS) is an uncommon autosomal recessive disorder chara cterized by premature aging. The clinical manifestations of WS, includ ing atherosclerosis and osteoporosis, appear early in adulthood, and d eath in the fourth to sixth decade commonly ensues from myocardial inf arction or cancer(1,2). In accord with the aging phenotype, cells from WS patients have a reduced replicative life span in culture(3), Genom ic instability is observed at the cytogenetic level in the form of chr omosome breaks and translocations(4) and at the molecular level by mul tiple large deletions(5). The Werner syndrome gene (WRN) has recently been cloned(6), The predicted product is a 1,432-amino-acid protein wh ose 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(7) and the human transcription-repair coupling factor CSB (Co ckayne syndrome B)(8) are highly homologous to known helicases, yet ne ither 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 ca talyze DNA unwinding.