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  • The EMBO Journal (2001) 20, 905 - 913
  • doi:10.1093/emboj/20.4.905

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

F. Brad Johnson1,2,3,8, Robert A. Marciniak1,3,4,8, Mitch McVey1, Sheila A. Stewart5, William C. Hahn5,6,7 and Leonard Guarente1

  1. Department of Biology, 68-280 Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
  2. Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA
  3. Department of Harvard Medical School, Boston, MA, USA
  4. Division of Hematology-Oncology, Massachusetts General Hospital, Boston, MA, USA
  5. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
  6. Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
  7. Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
  8. F.B.Johnson and R.A.Marciniak contributed equally to this work

Correspondence to:

Leonard Guarente, E-mail: leng@mit.edu

Received 19 October 2000; Accepted 19 December 2000; Revised 15 December 2000

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 loss of WRN leads to the phenotypes of WS is unknown. Cultured WS fibroblasts shorten their telomeres at an increased rate per population doubling and the premature senescence this loss induces can be bypassed by telomerase. Here we show that WRN co-localizes with telomeric factors in telomerase-independent immortalized human cells, and further that the budding yeast RecQ family helicase Sgs1p influences telomere metabolism in yeast cells lacking telomerase. Telomerase-deficient sgs1 mutants show increased rates of growth arrest in the G2/M phase of the cell cycle as telomeres shorten. In addition, telomerase-deficient sgs1 mutants have a defect in their ability to generate survivors of senescence that amplify telomeric TG1–3 repeats, and SGS1 functions in parallel with the recombination gene RAD51 to generate survivors. Our findings indicate that Sgs1p and WRN function in telomere maintenance, and suggest that telomere defects contribute to the pathogenesis of WS and perhaps other RecQ helicase diseases.

  • Keywords:

    • ALT,
    • replicative senescence,
    • SGS1,
    • telomeres,
    • Werner syndrome