Telomere Lagging Strand Synthesis Dysfunction in Cells Lacking WRN Helicase Activity

Werner syndrome is an autosomal recessive disease, and individuals suffering from the syndrome show all signs of premature ageing. 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 WRN localizes to telomeres in primary fibroblasts and that cells lacking WRN exhibit telomerase dependent telomere fusions. Werner syndrome cells suffer from the loss of individual telomeres during replication, and only telomeres replicated by lagging strand synthesis are affected. Our data suggest that loss of WRN causes a defect in replicating G rich telomeric DNA, resulting in telomere dysfunction of individual telomeres.