WRN at telomeres: implications for aging and cancer
Abstract
Werner Syndrome (WS) is a premature aging syndrome characterized by early onset of age-related pathologies and cancer. Since WS is due to a single gene defect, it has attracted much interest from researchers seeking to understand pathways that contribute to cancer and aging at cellular and molecular levels. The protein mutated in WS, WRN, appears to play a major role in genome stability, particularly during DNA replication and telomere metabolism. Much of the pathophysiology associated with WS, including the rapid onset of cellular senescence, early cancer onset and premature aging, can be attributed to a defect in telomere maintenance. Recent genetic evidence from the mTerc–/–Wrn–/– mouse demonstrates that mice with critically shortened telomeres display aging phenotypes reminiscent of human WS, further reinforcing the notion that telomere dysfunction is required for the manifestation of aging pathophysiologies in the setting of WRN deficiency.
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SIRT6 is required for the stable association of WRN, the factor mutated in Werner syndrome, at telomeric chromatin.
“At telomeric chromatin, SIRT6 deacetylates H3K9 and is required for the stable association of WRN, the factor that is mutated in Werner syndrome4,5.”
From SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin (2008) · cites this paper as [5]
SIRT6-depleted cells exhibit abnormal telomere structures that resemble defects observed in Werner syndrome.
“Moreover, SIRT6-depleted cells exhibit abnormal telomere structures that resemble defects observed in Werner syndrome, a premature ageing disorder4,5.”
From SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin (2008) · cites this paper as [5]
Cites
Shelterin: the protein complex that shapes and safeguards human telomeres
de Lange, T. (2005) · Genes & Development · doi:10.1101/gad.1346005 · Cited by 3,056 · see citing works
A DNA damage checkpoint response in telomere-initiated senescence
Fagagna, F. D. D., Reaper, P. M., Clay-Farrace, L., Fiegler, H., Carr, P., von Zglinicki, T., Saretzki, G., Carter, N. P., & Jackson, S. P. (2003) · Nature · doi:10.1038/nature02118 · Cited by 2,855 · see citing works
A survey of telomerase activity in human cancer
Shay, J. W., & Bacchetti, S. (1997) · European Journal of Cancer · doi:10.1016/s0959-8049(97)00062-2 · Cited by 2,794 · see citing works
Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors
Campisi, J. (2005) · Cell · doi:10.1016/j.cell.2005.02.003 · Cited by 2,359 · cited 1× · see citing works
“…derived from peripheral blood of humans over the age of 60 revealed that individuals possessing shorter telomeres than age-matched controls had significantly poorer survival rates, which was attributed in part to an elevated mortality rate from heart and infectious diseases (Cawthon et al., 2003).”
BackgroundCounter, C. M., Avilion, A. A., LeFeuvre, C. E., Stewart, N. G., Greider, C. W., Harley, C. B., & Bacchetti, S. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05245.x · Cited by 2,096 · cited 6× · see citing works
“2) (Crabbe et al., 2004).”
BackgroundInfluentialAssociation between telomere length in blood and mortality in people aged 60 years or older
Cawthon, R. M., Smith, K. R., O'Brien, E., Sivatchenko, A., & Kerber, R. A. (2003) · The Lancet · doi:10.1016/s0140-6736(03)12384-7 · Cited by 1,761 · see citing works
TRF2 Protects Human Telomeres from End-to-End Fusions
van Steensel, B., Smogorzewska, A., & de Lange, T. (1998) · Cell · doi:10.1016/s0092-8674(00)80932-0 · Cited by 1,709 · 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 3× · see citing works
“The mTerc–/– Wrn–/– compound mutant mouse as a model of human WS Extensive physiological analyses of telomerase-knockout mice revealed that late generation mTerc–/– animals that have short, dysfunctional telomeres exhibit decreased lifespan and a range of aging phenotypes including alopecia, hair greying, a reduced ca…”
BackgroundSelf-citationHemann, M. T., Strong, M. A., Hao, L.-Y., & Greider, C. W. (2001) · Cell · doi:10.1016/s0092-8674(01)00504-9 · Cited by 1,219 · see citing works
Cellular Senescence in Aging Primates
Herbig, U., Ferreira, M., Condel, L., Carey, D., & Sedivy, J. M. (2006) · Science · doi:10.1126/science.1122446 · Cited by 1,101 · see citing works
p53- and ATM-Dependent Apoptosis Induced by Telomeres Lacking TRF2
Karlseder, J., Broccoli, D., Dai, Y., Hardy, S., & de Lange, T. (1999) · Science · doi:10.1126/science.283.5406.1321 · Cited by 1,086 · see citing works
DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion
Celli, G. B., & de Lange, T. (2005) · Nature Cell Biology · doi:10.1038/ncb1275 · Cited by 623 · see citing works
Essential role of limiting telomeres in the pathogenesis of Werner syndrome
Chang, S., Multani, A. S., Cabrera, N. G., Naylor, M. L., Laud, P., Lombard, D., Pathak, S., Guarente, L., & DePinho, R. A. (2004) · Nature Genetics · doi:10.1038/ng1389 · Cited by 462 · see citing works
Self-citationYe, J. Z.-S., Hockemeyer, D., Krutchinsky, A. N., Loayza, D., Hooper, S. M., Chait, B. T., & de Lange, T. (2004) · Genes & Development · doi:10.1101/gad.1215404 · Cited by 459 · see citing works
PTOP interacts with POT1 and regulates its localization to telomeres
Liu, D., Safari, A., O'Connor, M. S., Chan, D. W., Laegeler, A., Qin, J., & Songyang, Z. (2004) · Nature Cell Biology · doi:10.1038/ncb1142 · Cited by 450 · see citing works
Wu, L., Multani, A. S., He, H., Cosme-Blanco, W., Deng, Y., Deng, J. M., Bachilo, O., Pathak, S., Tahara, H., Bailey, S. M., et al. (2006) · Cell · doi:10.1016/j.cell.2006.05.037 · Cited by 422 · see citing works
Self-citationTelomerase, Cell Immortality, and Cancer
Harley, C. B., Kim, N. W., Prowse, K. R., Weinrich, S. L., Hirsch, K. S., West, M. D., Bacchetti, S., Hirte, H. W., Counter, C. M., Greider, C. W., et al. (1994) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1994.059.01.035 · Cited by 396 · see citing works
In situ analyses of genome instability in breast cancer
Chin, K., de Solorzano, C. O., Knowles, D., Jones, A., Chou, W., Rodriguez, E. G., Kuo, W.-L., Ljung, B.-M., Chew, K., Myambo, K., et al. (2004) · Nature Genetics · doi:10.1038/ng1409 · Cited by 361 · see citing works
Telomerase 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
Celli, G. B., Denchi, E. L., & de Lange, T. (2006) · Nature Cell Biology · doi:10.1038/ncb1444 · Cited by 320 · see citing works
Significant Role for p16INK4a in p53-Independent Telomere-Directed Senescence
Jacobs, J. J. L., & de Lange, T. (2004) · Current Biology · doi:10.1016/j.cub.2004.12.025 · Cited by 237 · cited 1× · see citing works
“However, in human ALT cells a significant fraction of WRN appears to colocalize with TRF1 and TRF2 at telomeric DNA (Johnson et al., 2001; Opresko et al., 2002; Opresko et al., 2004).”
VASILE, E., TOMITA, Y., BROWN, L. F., KOCHER, O., & DVORAK, H. F. (2001) · The FASEB Journal · doi:10.1096/fj.00-0051com · Cited by 232 · 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
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Aubert, G., & Lansdorp, P. M. (2008) · Physiological Reviews · doi:10.1152/physrev.00026.2007 · Cited by 1,188 · see citing works
SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin
Michishita, E., McCord, R. A., Berber, E., Kioi, M., Padilla-Nash, H., Damian, M., Cheung, P., Kusumoto, R., Kawahara, T. L. A., Barrett, J. C., et al. (2008) · Nature · doi:10.1038/nature06736 · Cited by 1,111 · see citing works
A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging
Zhang, W., Li, J., Suzuki, K., Qu, J., Wang, P., Zhou, J., Liu, X., Ren, R., Xu, X., Ocampo, A., et al. (2015) · Science · doi:10.1126/science.aaa1356 · Cited by 551 · see citing works
Telomerase Protects Werner Syndrome Lineage-Specific Stem Cells from Premature Aging
Cheung, H.-H., Liu, X., Canterel-Thouennon, L., Li, L., Edmonson, C., & Rennert, O. M. (2014) · Stem Cell Reports · doi:10.1016/j.stemcr.2014.02.006 · Cited by 102 · see citing works
Progeroid Syndromes and UV-Induced Oxidative DNA Damage
Kamenisch, Y., & Berneburg, M. (2009) · Journal of Investigative Dermatology Symposium Proceedings · doi:10.1038/jidsymp.2009.6 · Cited by 50 · see citing works
- Authors
- Multani, A. S., & Chang, S.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Chang, Sandy
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2007-03-01
- Volume
- 120
- Issue
- 5
- Pages
- 713-721
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W1964881063
- Cited by
- 95
- References
- 23
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 1 · 2022: 5 · 2021: 4 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 2 · 2016: 2 · 2015: 6 · 2014: 3 · 2013: 5 · 2012: 4
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG028888)
- National Cancer Institute (R01CA129037)
- 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 › Nuclear Structure and Function
- Keywords
- Werner syndrome, WRN protein, telomeres, telomere maintenance, premature aging, cellular senescence, cancer susceptibility, genome stability, DNA replication, telomere dysfunction
- MeSH terms
- Werner Syndrome Helicase, Aging, Animals, Exodeoxyribonucleases, Humans, Models, Biological, Mutation, Neoplasms, Werner Syndrome, Telomere, RecQ Helicases
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