The Saccharomyces cerevisiae WRN homolog Sgs1p participates in telomere maintenance in cells lacking telomerase

Werner syndrome (WS) is marked by early onset of features resembling aging, and is caused by loss of the RecQ family DNA helicase WRN. Precisely how l oss of WRN leads to the phenotypes of WS is unknown. Cultured WS fibroblast s shorten their telomeres at an increased rate per population doubling and the premature senescence this loss induces can be bypassed by telomerase. H ere we show that WRN co-localizes with telomeric factors in telomerase-inde pendent immortalized human cells, and further that the budding yeast RecQ f amily helicase Sgs1p influences telomere metabolism in yeast cells lacking telomerase. Telomerase-deficient sgs1 mutants show increased rates of growt h arrest in the G(2)/M phase of the cell cycle as telomeres shorten. In add ition, telomerase-deficient sgs1 mutants have a defect in their ability to generate survivors of senescence that amplify telomeric TG(1-3) repeats, an d SGS1 functions in parallel with the recombination gene RAD51 to generate survivors. Our findings indicate that Sgs1p and WRN function in telomere ma intenance, and suggest that telomere defects contribute to the pathogenesis of WS and perhaps other RecQ helicase diseases.