PT - JOURNAL ARTICLE AU - Crabbe, Laure AU - Verdun, Ramiro E. AU - Haggblom, Candy I. AU - Karlseder, Jan TI - Defective Telomere Lagging Strand Synthesis in Cells Lacking WRN Helicase Activity AID - 10.1126/science.1103619 DP - 2004 Dec 10 TA - Science PG - 1951--1953 VI - 306 IP - 5703 4099 - http://science.sciencemag.org/content/306/5703/1951.short 4100 - http://science.sciencemag.org/content/306/5703/1951.full SO - Science2004 Dec 10; 306 AB - Cells from Werner syndrome patients are characterized by slow growth rates, premature senescence, accelerated telomere shortening rates, and genome instability. The syndrome is caused by the loss of the RecQ helicase WRN, but the underlying molecular mechanism is unclear. Here we report that cells lacking WRN exhibit deletion of telomeres from single sister chromatids. Only telomeres replicated by lagging strand synthesis were affected, and prevention of loss of individual telomeres was dependent on the helicase activity of WRN. Telomere loss could be counteracted by telomerase activity. We propose that WRN is necessary for efficient replication of G-rich telomeric DNA, preventing telomere dysfunction and consequent genomic instability.