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

F. Brad Johnson, Robert A Marciniak, Mitch McVey, Sheila A. Stewart, William C. Hahn, Leonard Guarente

Research output: Contribution to journalArticle

209 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)905-913
Number of pages9
JournalEMBO Journal
Volume20
Issue number4
DOIs
StatePublished - Feb 15 2001
Externally publishedYes

Fingerprint

Telomerase
Werner Syndrome
Telomere
Yeast
RecQ Helicases
Saccharomyces cerevisiae
Maintenance
Telomere Shortening
Cells
Defects
Saccharomycetales
G2 Phase
Fibroblasts
Metabolism
Cell Division
Genetic Recombination
Cell Cycle
Genes
Aging of materials
Yeasts

Keywords

  • ALT
  • Replicative senescence
  • SGS1
  • Telomeres
  • Werner syndrome

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

The Saccharomyces cerevisiae WRN homolog Sgs1p participates in telomere maintenance in cells lacking telomerase. / Johnson, F. Brad; Marciniak, Robert A; McVey, Mitch; Stewart, Sheila A.; Hahn, William C.; Guarente, Leonard.

In: EMBO Journal, Vol. 20, No. 4, 15.02.2001, p. 905-913.

Research output: Contribution to journalArticle

Johnson, F. Brad ; Marciniak, Robert A ; McVey, Mitch ; Stewart, Sheila A. ; Hahn, William C. ; Guarente, Leonard. / The Saccharomyces cerevisiae WRN homolog Sgs1p participates in telomere maintenance in cells lacking telomerase. In: EMBO Journal. 2001 ; Vol. 20, No. 4. pp. 905-913.
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AU - Guarente, Leonard

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AB - 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.

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