The Saccharomyces cerevisiae WRN homolog Sgs1p participates in telomere maintenance in cells lacking telomerase
Open accessAbstract
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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Sgs1p, the S. cerevisiae WRN homolog, is required for recombinational telomere maintenance in telomerase-deficient cells in yeast.
“Sgs1p, the S. cerevisiae WRN homolog, is required for recombinational telomere maintenance in telomerase-deficient cells in yeast (Cohen and Sinclair, 2001; Huang et al., 2001; Johnson et al., 2001”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as Johnson et al., 2001
WRN can be detected at the telomeres in the absence of telomerase function in mammalian cells.
“WRN can be detected at the telomeres in the absence of telomerase function in mammalian cells (Johnson et al., 2001; Opresko et al., 2004”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as Johnson et al., 2001
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Cites
Telomeres shorten during ageing of human fibroblasts
Harley, C. B., Futcher, A. B., & Greider, C. W. (1990) · Nature · doi:10.1038/345458a0 · Cited by 5,750 · see citing works
Extension of Life-Span by Introduction of Telomerase into Normal Human Cells
Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C.-P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., & Wright, W. E. (1998) · Science · doi:10.1126/science.279.5349.349 · Cited by 4,975 · see citing works
Creation of human tumour cells with defined genetic elements
Hahn, W. C., Counter, C. M., Lundberg, A. S., Beijersbergen, R. L., Brooks, M. W., & Weinberg, R. A. (1999) · Nature · doi:10.1038/22780 · Cited by 2,345 · see citing works
Self-citationTelomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA
Blasco, M. A., Lee, H.-W., Hande, M. P., Samper, E., Lansdorp, P. M., DePinho, R. A., & Greider, C. W. (1997) · Cell · doi:10.1016/s0092-8674(01)80006-4 · Cited by 2,108 · see citing works
Longevity, Stress Response, and Cancer in Aging Telomerase-Deficient Mice
Rudolph, K. L., Chang, S., Lee, H.-W., Blasco, M., Gottlieb, G. J., Greider, C., & DePinho, R. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80580-2 · Cited by 1,349 · cited 1× · see citing works
“Moreover, mice are relatively unaffected by the loss of telomerase: cultured mouse ®broblasts and intact mice lacking the mTR telomerase RNA show no evidence of senescence induced by telomere shortening and do not appear to incur pathologies until the point where telomeres become short enough to induce crisis (Blasco…”
BackgroundEssential role of mouse telomerase in highly proliferative organs
Lee, H.-W., Blasco, M. A., Gottlieb, G. J., Horner, J. W., Greider, C. W., & DePinho, R. A. (1998) · Nature · doi:10.1038/33345 · Cited by 1,270 · cited 1× · see citing works
“Moreover, mice are relatively unaffected by the loss of telomerase: cultured mouse ®broblasts and intact mice lacking the mTR telomerase RNA show no evidence of senescence induced by telomere shortening and do not appear to incur pathologies until the point where telomeres become short enough to induce crisis (Blasco…”
BackgroundVaziri, H., & Benchimol, S. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70109-5 · Cited by 1,003 · see citing works
Sherr, C. J., & DePinho, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)00046-5 · Cited by 745 · see citing works
Mills, K. D., Sinclair, D. A., & Guarente, L. (1999) · Cell · doi:10.1016/s0092-8674(00)80772-2 · Cited by 334 · see citing works
Self-citationTelomerase prevents the accelerated cell ageing of Werner syndrome fibroblasts
Wyllie, F. S., Jones, C. J., Skinner, J. W., Haughton, M. F., Wallis, C., Wynford-Thomas, D., Faragher, R. G. A., & Kipling, D. (2000) · Nature Genetics · doi:10.1038/71630 · Cited by 332 · see citing works
Schulz, V. P., Zakian, V. A., Ogburn, C. E., McKay, J., Jarzebowicz, A. A., Martin, G. M., & Edland, S. D. (1996) · Human Genetics · doi:10.1007/bf02346184 · Cited by 221 · see citing works
Park, P. U., Defossez, P.-A., & Guarente, L. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.5.3848 · Cited by 155 · cited 1× · see citing works
“SGS1 was deleted using the sgs1D::hisG-URA3 contruct pPP69 (Park et al., 1999).”
MethodSelf-citationTahara, H., Tokutake, Y., Maeda, S., Kataoka, H., Watanabe, T., Satoh, M., Matsumoto, T., Sugawara, M., Ide, T., Goto, M., et al. (1997) · Oncogene · doi:10.1038/sj.onc.1201377 · Cited by 130 · see citing works
Flagged first, then by citations
Research works printed but not linked: 9
- Counter,C.M., Hahn,W.C., Wei,W., Caddle,S.D., Beijersbergen,R.L., Lansdorp,P.M., Sedivy,J.M. and Weinberg,R.A. (1998) Dissociation among in vitro telomerase activity, telomere maintenance and cellular immortalization. Proc. Natl Acad. Sci. USA, 95, 14723±14728.
- Epstein,C.J., Martin,G.M., Schultz,A.L. and Motulsky,A.G. (1966) Werner's syndrome: a review of its symptomatology, natural history, pathologic features, genetics and relationship to the natural aging process. Medicine (Baltimore), 45, 177±221.
- Faragher,R.G., Kill,I.R., Hunter,J.A., Pope,F.M., Tannock,C. and Shall,S. (1993) The gene responsible for Werner syndrome may be a cell division `counting' gene. Proc. Natl Acad. Sci. USA, 90, 12030±12034.
- Hsu,H.L., Gilley,D., Blackburn,E.H. and Chen,D.J. (1999) Ku is associated with the telomere in mammals. Proc. Natl Acad. Sci. USA, 96, 12454±12458.
- Kamath-Loeb,A.S., Johansson,E., Burgers,P.M. and Loeb,L.A. (2000) Functional interaction between the Werner Syndrome protein and DNA polymerase d. Proc. Natl Acad. Sci. USA, 97, 4603±4608.
- Malkova,A., Ivanov,E.L. and Haber,J.E. (1996) Double-strand break repair in the absence of RAD51 in yeast: a possible role for break- induced DNA replication. Proc. Natl Acad. Sci. USA, 93, 7131±7136.
- Marciniak,R.A., Lombard,D.B., Johnson,F.B. and Guarente,L. (1998) Nucleolar localization of the Werner syndrome protein in human cells. Proc. Natl Acad. Sci. USA, 95, 6887±6892.
- Prowse,K.R. and Greider,C.W. (1995) Developmental and tissue-speci®c regulation of mouse telomerase and telomere length. Proc. Natl Acad. Sci. USA, 92, 4818±4822.
- Yamagata,K., Kato,J., Shimamoto,A., Goto,M., Furuichi,Y. and Ikeda,H. (1998) Bloom's and Werner's syndrome genes suppress hyperrecombination in yeast sgs1 mutant: implication for genomic instability in human diseases. Proc. Natl Acad. Sci. USA, 95, 8733±8738.
Cited by
Sorted by citations
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Lombard, D. B., Chua, K. F., Mostoslavsky, R., Franco, S., Gostissa, M., & Alt, F. W. (2005) · Cell · doi:10.1016/j.cell.2005.01.028 · Cited by 944 · see citing works
Opresko, P. L., Otterlei, M., Graakjær, J., Bruheim, P., Dawut, L., Kølvraa, S., May, A., Seidman, M. M., & Bohr, V. A. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.05.023 · Cited by 305 · see citing works
Laud, P. R., Multani, A. S., Bailey, S. M., Wu, L., Ma, J., Kingsley, C., Lebel, M., Pathak, S., DePinho, R. A., & Chang, S. (2005) · Genes & Development · doi:10.1101/gad.1321305 · Cited by 190 · see citing works
Short Telomeres Induce a DNA Damage Response in<i>Saccharomyces cerevisiae</i>
IJpma, A. S., & Greider, C. W. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.02-04-0057 · Cited by 178 · see citing works
TRF2 recruits the Werner syndrome (WRN) exonuclease for processing of telomeric DNA
Machwe, A., Xiao, L., & Orren, D. K. (2004) · Oncogene · doi:10.1038/sj.onc.1206906 · Cited by 130 · see citing works
The Werner syndrome helicase/exonuclease (WRN) disrupts and degrades D-loops in vitro
Orren, D. K., Theodore, S., & Machwe, A. (2002) · Biochemistry · doi:10.1021/bi0266986 · Cited by 112 · see citing works
The genome-wide expression response to telomerase deletion in <i>Saccharomyces</i> <i>cerevisiae</i>
Nautiyal, S., DeRisi, J. L., & Blackburn, E. H. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.142162499 · Cited by 96 · see citing works
Wang, H., Chen, Q., Lee, S., Choi, Y., Brad Johnson, F., & Pignolo, R. J. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00838.x · Cited by 81 · see citing works
Brennan, T. A., Egan, K. P., Lindborg, C. M., Chen, Q., Sweetwyne, M. T., Hankenson, K. D., Xie, S. X., Johnson, F. B., & Pignolo, R. J. (2014) · Disease Models & Mechanisms · doi:10.1242/dmm.014928 · Cited by 45 · see citing works
Self-citationWerner syndrome protein: Functions in the response to DNA damage and replication stress in S-phase
Cheng, W.-H., Muftuoglu, M., & Bohr, V. A. (2007) · Experimental Gerontology · doi:10.1016/j.exger.2007.04.011 · Cited by 30 · see citing works
- Authors
- Johnson, F. B., Marciniak, R. A., McVey, M., Stewart, S. A., Hahn, W. C., & Guarente, L.
- Affiliations
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Massachusetts Institute of Technology (US)
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Guarente, Leonard
- Venue
- The EMBO Journal
- Published
- 2001-02-15
- Volume
- 20
- Issue
- 4
- Pages
- 905-913
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC145415
- OpenAlex
- W2118991749
- Cited by
- 269
- References
- 13
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 7 · 2023: 4 · 2022: 3 · 2021: 6 · 2020: 3 · 2019: 5 · 2018: 6 · 2017: 5 · 2016: 8 · 2015: 2 · 2014: 8 · 2013: 9 · 2012: 8
- FWCI
- 19.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ellison Medical Foundation
- National Institutes of Health
- National Institute on Aging
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- WRN, Werner syndrome, RecQ helicase, telomere maintenance, telomerase deficiency, telomere shortening, premature senescence, G2/M cell cycle arrest, RAD51, Saccharomyces cerevisiae
- MeSH terms
- DNA Helicases, DNA-Binding Proteins, Humans, Phenotype, Saccharomyces cerevisiae, Telomere, Telomerase, Saccharomyces cerevisiae Proteins, Rad51 Recombinase, RecQ Helicases
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