Mammalian Telomeres End in a Large Duplex Loop
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Mammalian telomeres contain a duplex array of telomeric repeats bound to the telomeric repeat-binding factors TRF1 and TRF2. Inhibition of TRF2 results in immediate deprotection of chromosome ends, manifested by loss of the telomeric 3' overhang, activation of p53, and end-to-end chromosome fusions. Electron microscopy reported here demonstrated that TRF2 can remodel linear telomeric DNA into large duplex loops (t loops) in vitro. Electron microscopy analysis of psoralen cross-linked telomeric DNA purified from human and mouse cells revealed abundant large t loops with a size distribution consistent with their telomeric origin. Binding of TRF1 and single strand binding protein suggested that t loops are formed by invasion of the 3' telomeric overhang into the duplex telomeric repeat array. T loops may provide a general mechanism for the protection and replication of telomeres.
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Progressive loss of telomere repeats displaces shelterin components and destabilizes the t-loop, exposing the telomere end, which is recognized as a double-strand DNA break.
“It has been hypothesized that with the progressive loss of telomere repeats with cell division due to the “end-replication problem”, shelterin components may be displaced from telomere regions and subsequently destabilize the abovementioned t-loop conformation (Griffith et al., 1999). This results in the exposure of the telomere end, which becomes recognized by the DNA repair machinery as a double”
From Telomeres and cell senescence—size matters not (2017) · cites this paper as Griffith et al., 1999
The 3′ overhang binds to a double-stranded DNA region and facilitates t-loop formation.
“The overhang is thought to bind to one of the double-stranded DNA regions and facilitate the formation of the t-loop structure (Griffith et al., 1999).”
From Telomeres and cell senescence—size matters not (2017) · cites this paper as Griffith et al., 1999
Telomere shortening precipitates the loss of shelterin components and destabilization of the t-loop conformation, resulting in exposure of the telomere end.
“It is thought that with each cell division, telomere shortening precipitates the loss of “shelterin” components and the destabilization of the t-loop conformation, resulting in exposure of the telomere end (Griffith et al., 1999).”
From Stress, cell senescence and organismal ageing (2018) · cites this paper as Griffith et al., 1999
Telomeres are repetitive DNA sequences bound by the six-subunit shelterin complex that facilitates the formation of telomere loops to hide the telomere end, thus protecting chromosome ends from DNA break signaling pathways.
“Telomeres are repetitive DNA sequences, bound by the six-subunit shelterin complex [86] that facilitates the formation of telomere loops (t-loop) to hide the telomere end [87,88], thus protecting the natural chromosome ends from signaling pathways that sense and act at DNA breaks.”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [87]
The single-stranded overhang can fold back on the double-stranded telomere to form a t-loop that sequesters the chromosome end.
“The single-stranded overhang can fold back on the double-stranded telomere in a lariat structure termed the t-loop, which serves to sequester the chromosome terminus (2).”
From Telomeres and telomerase in cancer (2010) · cites this paper as [2]
Telomeres can adopt a looped conformation called the t-loop, in which the single-stranded overhang folds back onto the double-stranded telomere to sequester the end.
“Telomeres can exist in a looped conformation, termed the t-loop, in which the single-stranded overhang folds back on the double-stranded telomere to sequester the end.”
From Telomeres and telomerase in cancer (2010) · cites this paper as Griffith,J.D. et al. (1999)
TRF1 displays extensive binding along the duplex telomeric DNA even when the DNA is in the t loop configuration.
“This preference for the t loop junction was not observed for TRF1 which displayed extensive binding along the duplex telomeric DNA even when the DNA was in the t loop configuration.”
From Control of Human Telomere Length by TRF1 and TRF2 (2000) · cites this paper as [21]
When TRF2 is associated with telomeric DNA in the t loop configuration, it is preferentially positioned on or near the t loop junction rather than along the telomeric tract.
“However, electron microscope analysis indicated that when TRF2 is associated with telomeric DNA in the t loop configuration, it is preferentially positioned on or near the t loop junction rather than along the telomeric tract (21).”
From Control of Human Telomere Length by TRF1 and TRF2 (2000) · cites this paper as [21]
TRF2 induces the invasion of the 3′ single-stranded TTAGGG repeat tail into duplex telomeric DNA, forming t loops in vitro.
“TRF2 was found to induce the invasion of the 3′ single-stranded TTAGGG repeat tail into duplex telomeric DNA, forming t loops in vitro (21; R. Stansel, T. de Lange, and J. D. Griffith, unpublished data).”
From Control of Human Telomere Length by TRF1 and TRF2 (2000) · cites this paper as [21]
Rap1p and TRF2 display intriguing similarities in biochemical activities relevant to telomere looping.
“Rap1p and TRF2 display intriguing similarities in biochemical activities that are relevant to telomere looping (17, 18, 21).”
From Control of Human Telomere Length by TRF1 and TRF2 (2000) · cites this paper as [21]
HeLal.2.11 has telomeres of approximately 15 to 40 kb.
“HeLal.2.11 has telomeres of approximately 15 to 40 kb (21), whereas HeLall has shorter telomeres ranging from 3 to 6.5 kb (6 kb median) (39).”
From Control of Human Telomere Length by TRF1 and TRF2 (2000) · cites this paper as [21]
The telomere 3′ single-stranded overhang can invade double-stranded telomeric tracts, displacing the homologous strand, forming a t-loop with a displacement loop at the invasion site.
“Analysis of telomeres from a diverse array of organisms revealed that the telomere 3′ single-stranded overhang can invade the double-stranded telomeric tracts, displacing the homologous strand of the same telomere. Consequently, a telomere forms a lasso-like structure, termed the ‘t-loop’, with a displacement (D) loop at the invasion site12, 13”
From Telomere dysfunction and tumour suppression: the senescence connection (2008) · cites this paper as [12]
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
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 · see citing works
Essential 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
“, 1997), is essential for long-term replicative survival of cells in vitro, and a telomerase-deficient Summary mouse strain displays several phenotypes consistent with impaired tissue homeostasis (Lee et al., 1998; RuMammalian telomeres contain a duplex array of telodolph et al., 1999).”
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
Telomerase activity in human ovarian carcinoma.
Counter, C. M., Hirte, H. W., Bacchetti, S., & Harley, C. B. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.8.2900 · Cited by 677 · cited 4× · see citing works
“However, other Although the telomeric repeat array remains largely intact, the single-stranded protrusion of TTAGGG repeats‡ To whom correspondence should be addressed (e-mail: jdg@ found at all mammalian telomeres (Makarov et al., 1997)med.unc.edu). is lost upon inhibition of TRF2, suggesting that the G§ Present addr…”
BackgroundInfluentialTRF1 is a dimer and bends telomeric DNA
Bianchi, A., Smith, S., Chong, L., Elias, P., & de Lange, T. (1997) · The EMBO Journal · doi:10.1093/emboj/16.7.1785 · Cited by 358 · see citing works
Self-citationTRF1 promotes parallel pairing of telomeric tracts in vitro
Griffith, J., Bianchi, A., & de Lange, T. (1998) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.1686 · Cited by 148 · see citing works
Self-citation
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Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441 · see citing works
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
Hemann, 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
Aubert, G., & Lansdorp, P. M. (2008) · Physiological Reviews · doi:10.1152/physrev.00026.2007 · Cited by 1,188 · see citing works
The importance of repairing stalled replication forks
Cox, M. M., Goodman, M. F., Kreuzer, K. N., Sherratt, D. J., Sandler, S. J., & Marians, K. J. (2000) · Nature · doi:10.1038/35003501 · Cited by 1,044 · see citing works
Pot1, the Putative Telomere End-Binding Protein in Fission Yeast and Humans
Baumann, P., & Cech, T. R. (2001) · Science · doi:10.1126/science.1060036 · Cited by 1,028 · see citing works
Protection of mammalian telomeres
de Lange, T. (2002) · Oncogene · doi:10.1038/sj.onc.1205080 · Cited by 942 · see citing works
Hewitt, G., Jurk, D., Marques, F. D. M., Correia-Melo, C., Hardy, T., Gackowska, A., Anderson, R., Taschuk, M., Mann, J., & Passos, J. F. (2012) · Nature Communications · doi:10.1038/ncomms1708 · Cited by 908 · see citing works
Human Telomerase and Its Regulation
Cong, Y.-S., Wright, W. E., & Shay, J. W. (2002) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.66.3.407-425.2002 · Cited by 898 · see citing works
Telomere maintenance by recombination in human cells
Dunham, M. A., Neumann, A. A., Fasching, C. L., & Reddel, R. R. (2000) · Nature Genetics · doi:10.1038/82586 · Cited by 879 · see citing works
Shelterin-Mediated Telomere Protection
de Lange, T. (2018) · Annual Review of Genetics · doi:10.1146/annurev-genet-032918-021921 · Cited by 816 · see citing works
Self-citationThe MRE11 complex: at the crossroads of DNA repair and checkpoint signalling
D'Amours, D., & Jackson, S. P. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm805 · Cited by 874 · see citing works
How Telomeres Solve the End-Protection Problem
de Lange, T. (2009) · Science · doi:10.1126/science.1170633 · Cited by 826 · see citing works
Self-citationSenescence Induced by Altered Telomere State, Not Telomere Loss
Karlseder, J., Smogorzewska, A., & de Lange, T. (2002) · Science · doi:10.1126/science.1069523 · Cited by 796 · see citing works
Control of Human Telomere Length by TRF1 and TRF2
Smogorzewska, A., van Steensel, B., Bianchi, A., Oelmann, S., Schaefer, M. R., Schnapp, G., & de Lange, T. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.5.1659-1668.2000 · Cited by 768 · see citing works
Self-citationPhotoageing: mechanism, prevention and therapy
Yaar, M., & Gilchrest, B. A. (2007) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2007.08108.x · Cited by 755 · see citing works
Telomere length, stem cells and aging
Blasco, M. A. (2007) · Nature Chemical Biology · doi:10.1038/nchembio.2007.38 · Cited by 747 · see citing works
Toussaint, O., Medrano, E. E., & von Zglinicki, T. (2000) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00180-7 · Cited by 713 · see citing works
McEachern, M. J., Krauskopf, A., & Blackburn, E. H. (2000) · Annual Review of Genetics · doi:10.1146/annurev.genet.34.1.331 · Cited by 716 · see citing works
Role of Telomeres and Telomerase in Aging and Cancer
Shay, J. W. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0062 · Cited by 668 · see citing works
Telomeres: history, health, and hallmarks of aging
Chakravarti, D., LaBella, K. A., & DePinho, R. A. (2021) · Cell · doi:10.1016/j.cell.2020.12.028 · Cited by 637 · 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
Accumulation of single-strand breaks is the major cause of telomere shortening in human fibroblasts
von Zglinicki, T., Pilger, R., & Sitte, N. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00207-5 · Cited by 546 · see citing works
Teixeira, M. T., Arneric, M., Sperisen, P., & Lingner, J. (2004) · Cell · doi:10.1016/s0092-8674(04)00334-4 · Cited by 526 · see citing works
Length-independent telomere damage drives post-mitotic cardiomyocyte senescence
Anderson, R., Lagnado, A., Maggiorani, D., Walaszczyk, A., Dookun, E., Chapman, J., Birch, J., Salmonowicz, H., Ogrodnik, M., Jurk, D., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2018100492 · Cited by 532 · see citing works
“The current dogma of telomere biology suggests that telomere shortening with each successive cell division eventually disrupts the protective cap, leading to a sustained DNA damage response (DDR) and activation of the senescence programme (Griffith et al , 1999).”
TIN2, a new regulator of telomere length in human cells
Kim, S.-H., Kaminker, P., & Campisi, J. (1999) · Nature Genetics · doi:10.1038/70508 · Cited by 525 · see citing works
Super-Resolution Fluorescence Imaging of Telomeres Reveals TRF2-Dependent T-loop Formation
Doksani, Y., Wu, J. Y., de Lange, T., & Zhuang, X. (2013) · Cell · doi:10.1016/j.cell.2013.09.048 · Cited by 493 · see citing works
Hallmarks of senescence in carcinogenesis and cancer therapy
Shay, J. W., & Roninson, I. B. (2004) · Oncogene · doi:10.1038/sj.onc.1207518 · Cited by 502 · see citing works
Different telomere damage signaling pathways in human and mouse cells
Smogorzewska, A., & de Lange, T. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf433 · Cited by 482 · see citing works
Markers of cellular senescence. Telomere shortening as a marker of cellular senescence
Bernadotte, A., Mikhelson, V. M., & Spivak, I. M. (2016) · Aging · doi:10.18632/aging.100871 · Cited by 466 · see citing works
Replication and protection of telomeres
Verdun, R. E., & Karlseder, J. (2007) · Nature · doi:10.1038/nature05976 · Cited by 463 · see citing works
T-loops and the origin of telomeres
de Lange, T. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1359 · Cited by 461 · see citing works
Telomerase contributes to tumorigenesis by a telomere length-independent mechanism
Stewart, S. A., Hahn, W. C., O'Connor, B. F., Banner, E. N., Lundberg, A. S., Modha, P., Mizuno, H., Brooks, M. W., Fleming, M., Zimonjic, D. B., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.182407599 · Cited by 431 · see citing works
Dasika, G. K., Lin, S.-C. J., Zhao, S., Sung, P., Tomkinson, A., & Lee, E. Y.-H. P. (1999) · Oncogene · doi:10.1038/sj.onc.1203283 · Cited by 427 · see citing works
Human cell senescence as a DNA damage response
Zglinicki, T. V., Saretzki, G., Ladhoff, J., Fagagna, F. D. D., & Jackson, S. P. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2004.09.034 · Cited by 419 · see citing works
Telomeres and cell senescence—size matters not
Victorelli, S., & Passos, J. F. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.03.027 · Cited by 413 · 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
Telomere dysfunction and tumour suppression: the senescence connection
Deng, Y., Chan, S. S., & Chang, S. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2393 · Cited by 411 · see citing works
Telosome, a Mammalian Telomere-associated Complex Formed by Multiple Telomeric Proteins
Liu, D., O'Connor, M. S., Qin, J., & Songyang, Z. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m409293200 · Cited by 405 · see citing works
Mechanisms and Regulation of Cellular Senescence
Roger, L., Tomas, F., & Gire, V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222313173 · Cited by 395 · see citing works
Cellular senescence, cancer and aging: the telomere connection
Campisi, J., Kim, S.-H., Lim, C.-S., & Rubio, M. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00160-7 · Cited by 400 · see citing works
Telomerase-Mediated Telomere Addition In Vivo Requires DNA Primase and DNA Polymerases α and δ
Diede, S. J., & Gottschling, D. E. (1999) · Cell · doi:10.1016/s0092-8674(00)81670-0 · Cited by 379 · see citing works
Regulation of cellular senescence by p53
Itahana, K., Dimri, G., & Campisi, J. (2001) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2001.02228.x · Cited by 365 · see citing works
When cells get stressed: an integrative view of cellular senescence
Ben-Porath, I., & Weinberg, R. A. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200420663 · Cited by 404 · see citing works
Forsyth, N. R., Wright, W. E., & Shay, J. W. (2002) · Differentiation · doi:10.1046/j.1432-0436.2002.690412.x · Cited by 345 · see citing works
Aubert, G., Hills, M., & Lansdorp, P. M. (2012) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2011.04.003 · Cited by 342 · see citing works
Mechanisms of cellular senescence in human and mouse cells.
Itahana, K., Campisi, J., & Dimri, G. P. (2004) · Biogerontology · doi:10.1023/b:bgen.0000017682.96395.10 · Cited by 338 · see citing works
Erosion of the telomeric single-strand overhang at replicative senescence
Stewart, S. A., Ben-Porath, I., Carey, V. J., O'Connor, B. F., Hahn, W. C., & Weinberg, R. A. (2003) · Nature Genetics · doi:10.1038/ng1127 · Cited by 335 · see citing works
Stress, cell senescence and organismal ageing
de Magalhães, J. P., & Passos, J. F. (2018) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.07.001 · Cited by 316 · 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
Regulation of Murine Telomere Length by Rtel
Ding, H., Schertzer, M., Wu, X., Gertsenstein, M., Selig, S., Kammori, M., Pourvali, R., Poon, S., Vulto, I., Chavez, E., et al. (2004) · Cell · doi:10.1016/j.cell.2004.05.026 · Cited by 309 · see citing works
Hockemeyer, D., Sfeir, A. J., Shay, J. W., Wright, W. E., & de Lange, T. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600733 · Cited by 314 · see citing works
Short Telomeres, even in the Presence of Telomerase, Limit Tissue Renewal Capacity
Hao, L.-Y., Armanios, M., Strong, M. A., Karim, B., Feldser, D. M., Huso, D., & Greider, C. W. (2005) · Cell · doi:10.1016/j.cell.2005.11.020 · Cited by 302 · 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
Hug, N., & Lingner, J. (2006) · Chromosoma · doi:10.1007/s00412-006-0067-3 · Cited by 291 · see citing works
Oh, H., Taffet, G. E., Youker, K. A., Entman, M. L., Overbeek, P. A., Michael, L. H., & Schneider, M. D. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.191169098 · Cited by 289 · see citing works
Oxidative damage in telomeric DNA disrupts recognition by TRF1 and TRF2
Opresko, P. L. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki273 · Cited by 289 · see citing works
Functional Human Telomeres Are Recognized as DNA Damage in G2 of the Cell Cycle
Verdun, R. E., Crabbe, L., Haggblom, C., & Karlseder, J. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.09.024 · Cited by 284 · see citing works
Functional links between telomeres and proteins of the DNA-damage response
d'Adda di Fagagna, F., Teo, S.-H., & Jackson, S. P. (2004) · Genes & Development · doi:10.1101/gad.1214504 · Cited by 277 · see citing works
Accumulation of Short Telomeres in Human Fibroblasts Prior to Replicative Senescence
Martens, U. M., Chavez, E. A., Poon, S. S. S., Schmoor, C., & Lansdorp, P. M. (2000) · Experimental Cell Research · doi:10.1006/excr.2000.4823 · Cited by 263 · see citing works
Telomere damage induced by the G-quadruplex ligand RHPS4 has an antitumor effect
Salvati, E., Leonetti, C., Rizzo, A., Scarsella, M., Mottolese, M., Galati, R., Sperduti, I., Stevens, M. F. G., D’Incalci, M., Blasco, M., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32461 · Cited by 266 · see citing works
Dysfunctional telomeres activate an ATM‐ATR‐dependent DNA damage response to suppress tumorigenesis
Guo, X., Deng, Y., Lin, Y., Cosme‐Blanco, W., Chan, S., He, H., Yuan, G., Brown, E. J., & Chang, S. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601893 · Cited by 258 · see citing works
Telomere-driven diseases and telomere-targeting therapies
Martínez, P., & Blasco, M. A. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201610111 · Cited by 257 · see citing works
“1, A and B; Griffith et al., 1999; Doksani et al., 2013).”
BackgroundSenescent human melanocytes drive skin ageing via paracrine telomere dysfunction
Victorelli, S., Lagnado, A., Halim, J., Moore, W., Talbot, D., Barrett, K., Chapman, J., Birch, J., Ogrodnik, M., Meves, A., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2019101982 · Cited by 258 · see citing works
Zhu, Y., Liu, X., Ding, X., Wang, F., & Geng, X. (2019) · Biogerontology · doi:10.1007/s10522-018-9769-1 · Cited by 255 · see citing works
Pif1p Helicase, a Catalytic Inhibitor of Telomerase in Yeast
Zhou, J.-Q., Monson, E. K., Teng, S.-C., Schulz, V. P., & Zakian, V. A. (2000) · Science · doi:10.1126/science.289.5480.771 · Cited by 236 · see citing works
Five dysfunctional telomeres predict onset of senescence in human cells
Kaul, Z., Cesare, A. J., Huschtscha, L. I., Neumann, A. A., & Reddel, R. R. (2012) · The EMBO Reports · doi:10.1038/embor.2011.227 · Cited by 225 · see citing works
“Telomeres can adopt a loop (t-loop) structure (Griffith et al , 1999).”
Mammalian telomeres and telomerase
Collins, K. (2000) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00103-4 · Cited by 226 · see citing works
A RAP1/TRF2 Complex Inhibits Nonhomologous End-Joining at Human Telomeric DNA Ends
Bae, N. S., & Baumann, P. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.03.023 · Cited by 215 · see citing works
TRF1 binds a bipartite telomeric site with extreme spatial flexibility
Bianchi, A., Stansel, R. M., Fairall, L., Griffith, J. D., Rhodes, D., & de Lange, T. (1999) · The EMBO Journal · doi:10.1093/emboj/18.20.5735 · Cited by 217 · see citing works
Self-citationTelomere shortening in human diseases
Kong, C. M., Lee, X. W., & Wang, X. (2013) · The FEBS Journal · doi:10.1111/febs.12326 · Cited by 194 · see citing works
Vascular smooth muscle cell senescence in atherosclerosis
GORENNE, I., KAVURMA, M., SCOTT, S., & BENNETT, M. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.06.004 · Cited by 196 · see citing works
SGS1 is required for telomere elongation in the absence of telomerase
Huang, P.-H., Pryde, F. E., Lester, D., Maddison, R. L., Borts, R. H., Hickson, I. D., & Louis, E. J. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00021-5 · Cited by 185 · see citing works
Telomeropathies: An emerging spectrum disorder
Holohan, B., Wright, W. E., & Shay, J. W. (2014) · Journal of Cell Biology · doi:10.1083/jcb.201401012 · Cited by 175 · see citing works
Blasco, M. A. (2002) · Nature Reviews Cancer · doi:10.1038/nrc862 · Cited by 175 · see citing works
DNA damage response at telomeres contributes to lung aging and chronic obstructive pulmonary disease
Birch, J., Anderson, R. K., Correia-Melo, C., Jurk, D., Hewitt, G., Marques, F. M., Green, N. J., Moisey, E., Birrell, M. A., Belvisi, M. G., et al. (2015) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00293.2015 · Cited by 174 · see citing works
The Telomere Deprotection Response Is Functionally Distinct from the Genomic DNA Damage Response
Cesare, A. J., Hayashi, M. T., Crabbe, L., & Karlseder, J. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.06.006 · Cited by 155 · see citing works
Impact of oxidative stress on telomere biology
Ahmed, W., & Lingner, J. (2018) · Differentiation · doi:10.1016/j.diff.2017.12.002 · Cited by 153 · see citing works
Ageing induced vascular smooth muscle cell senescence in atherosclerosis
Uryga, A. K., & Bennett, M. R. (2016) · The Journal of Physiology · doi:10.1113/jp270923 · Cited by 160 · see citing works
Armstrong, L., Saretzki, G., Peters, H., Wappler, I., Evans, J., Hole, N., von Zglinicki, T., & Lako, M. (2005) · Stem Cells · doi:10.1634/stemcells.2004-0269 · Cited by 153 · see citing works
Cancer and aging: the importance of telomeres in genome maintenance
Rodier, F., Kim, S.-H., Nijjar, T., Yaswen, P., & Campisi, J. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2004.10.012 · Cited by 132 · 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
Telomeres and immunological diseases of aging.
Andrews, N. P., Fujii, H., Goronzy, J. J., & Weyand, C. M. (2010) · Gerontology · doi:10.1159/000268620 · Cited by 108 · see citing works
USP7 Is a Master Regulator of Genome Stability
Valles, G. J., Bezsonova, I., Woodgate, R., & Ashton, N. W. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00717 · Cited by 114 · see citing works
“These structures form when the telomeric ssDNA overhang invades an upstream region of the telomere duplex and stably binds via complementarity of the hexanucleotide sequence (Griffith et al., 1999).”
BackgroundMorgan, R. G., Ives, S. J., Lesniewski, L. A., Cawthon, R. M., Andtbacka, R. H. I., Noyes, R. D., Richardson, R. S., & Donato, A. J. (2013) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00197.2013 · Cited by 115 · see citing works
A three-state model of telomere control over human proliferative boundaries
Cesare, A. J., & Karlseder, J. (2012) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2012.08.007 · Cited by 106 · see citing works
Gong, Y., & de Lange, T. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.10.016 · Cited by 102 · see citing works
Self-citationCellular lifespan and senescence signaling in embryonic stem cells
Miura, T., Mattson, M. P., & Rao, M. S. (2004) · Aging Cell · doi:10.1111/j.1474-9728.2004.00134.x · Cited by 102 · see citing works
Reconstructing the in vivo dynamics of hematopoietic stem cells from telomere length distributions
Werner, B., Beier, F., Hummel, S., Balabanov, S., Lassay, L., Orlikowsky, T., Dingli, D., Brümmendorf, T. H., & Traulsen, A. (2015) · eLife · doi:10.7554/elife.08687 · Cited by 95 · see citing works
Ludlow, A. T., Ludlow, L. W., & Roth, S. M. (2013) · BioMed Research International · doi:10.1155/2013/601368 · Cited by 93 · see citing works
TRF2/RAP1 and DNA-PK mediate a double protection against joining at telomeric ends
Bombarde, O., Boby, C., Gomez, D., Frit, P., Giraud‐Panis, M., Gilson, E., Salles, B., & Calsou, P. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.49 · Cited by 89 · see citing works
Role of TERRA in the regulation of telomere length
Wang, C., Zhao, L., & Lu, S. (2015) · International Journal of Biological Sciences · doi:10.7150/ijbs.10528 · Cited by 89 · see citing works
Replicative senescence revisited.
Marcotte, R., & Wang, E. (2002) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/57.7.b257 · Cited by 86 · see citing works
Contributions of DNA interstrand cross-links to aging of cells and organisms
Grillari, J., Katinger, H., & Voglauer, R. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm1065 · Cited by 83 · see citing works
The mitochondrial genome in aging and senescence
Lauri, A., Pompilio, G., & Capogrossi, M. C. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.07.001 · Cited by 80 · see citing works
Homologous recombination-dependent repair of telomeric DSBs in proliferating human cells
Mao, P., Liu, J., Zhang, Z., Zhang, H., Liu, H., Gao, S., Rong, Y. S., & Zhao, Y. (2016) · Nature Communications · doi:10.1038/ncomms12154 · Cited by 76 · see citing works
Hiding at the ends of yeast chromosomes: Telomeres, nucleases and checkpoint pathways
Lydall, D. (2003) · Journal of Cell Science · doi:10.1242/jcs.00765 · Cited by 72 · see citing works
Telomerase Maintains Telomere Structure in Normal Human Cells
Masutomi, K., Yu, E. Y., Khurts, S., Ben-Porath, I., Currier, J. L., Metz, G. B., Brooks, M. W., Kaneko, S., Murakami, S., DeCaprio, J. A., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00550-6 · Cited by 70 · see citing works
Sławińska, N., & Krupa, R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020590 · Cited by 68 · see citing works
DNA damage repair: anytime, anywhere?
Essers, J., Vermeulen, W., & Houtsmuller, A. B. (2006) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2006.03.004 · Cited by 67 · see citing works
- Authors
- Griffith, J. D., Comeau, L., Rosenfield, S., Stansel, R. M., Bianchi, A., Moss, H., & de Lange, T.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Rockefeller University (US)
- Corresponding author
- Griffith, Jack D
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1999-05
- Volume
- 97
- Issue
- 4
- Pages
- 503-514
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2032407757
- Cited by
- 2,447
- References
- 9
- Citations by year
- 2026: 26 · 2025: 43 · 2024: 71 · 2023: 63 · 2022: 61 · 2021: 82 · 2020: 74 · 2019: 77 · 2018: 69 · 2017: 60 · 2016: 84 · 2015: 88 · 2014: 96 · 2013: 97 · 2012: 80
- FWCI
- 62.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Sussex Research Online (University of Sussex) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- National Cancer Institute (CA19043)
- National Institute of General Medical Sciences (GM 49046, GM-31819, R01GM031819)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- telomeres, T-loop, TRF2, TRF1, telomeric overhangs, chromosome end protection, telomere replication, single-stranded DNA binding protein, chromosome fusion, p53 activation, DNA loop formation
- MeSH terms
- Animals, Cross-Linking Reagents, DNA, DNA-Binding Proteins, HeLa Cells, Humans, Mammals, Models, Molecular, Nucleic Acid Heteroduplexes, Recombinant Fusion Proteins, Telomere, Telomeric Repeat Binding Protein 1, Telomeric Repeat Binding Protein 2, Mice
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