The nature of telomere fusion and a definition of the critical telomere length in human cells
Open accessAbstract
The loss of telomere function can result in telomeric fusion events that lead to the types of genomic rearrangements, such as nonreciprocal translocations, that typify early-stage carcinogenesis. By using single-molecule approaches to characterize fusion events, we provide a functional definition of fusogenic telomeres in human cells. We show that approximately half of the fusion events contained no canonical telomere repeats at the fusion point; of those that did, the longest was 12.8 repeats. Furthermore, in addition to end-replication losses, human telomeres are subjected to large-scale deletion events that occur in the presence or absence of telomerase. Here we show that these telomeres are fusogenic, and thus despite the majority of telomeres being maintained at a stable length in normal human cells, a subset of stochastically shortened telomeres can potentially cause chromosomal instability. Telomere fusion was accompanied by the deletion of one or both telomeres extending several kilobases into the telomere-adjacent DNA, and microhomology was observed at the fusion points. This contrasted with telomere fusion that was observed following the experimental disruption of TRF2. The distinct error-prone mutational profile of fusion between critically shortened telomeres in human cells was reminiscent of Ku-independent microhomology-mediated end-joining.
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The segmental aneuploidies identified by cytogenetics analysis most probably point to the occurrence of complex genomic rearrangements in OCT4-targeted samples, such as chromosomal translocations or end-to-end fusions.
“The segmental aneuploidies identified by cytogenetics analysis (Figs. 1B and S3-S5) most probably point to the occurrence of complex genomic rearrangements in OCT4-targeted samples, such as chromosomal translocations or end-to-end fusions, as it seems unlikely that the rest of the chromosome would continue to be retained without a telomere (31)(32)(33).”
From Frequent loss of heterozygosity in CRISPR-Cas9–edited early human embryos (2021) · cites this paper as [33]
Telomere fusions formed during telomere crisis in cultured cells are mediated by alt-NHEJ and show insertion of new sequences at the fusion point.
“Telomere fusions formed during telomere crisis in cultured cells are mediated by alt-NHEJ and exhibit insertion of new sequences at the fusion point75,76.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [75]
Evidence for past telomere crisis has been obtained in chronic lymphocytic leukaemia, breast cancer, colorectal adenomas, and other solid tumours using a PCR-based assay for telomere-telomere fusions.
“Using this approach, evidence for past telomere crisis has been obtained in CLL as well as in breast cancer, colorectal adenomas and other solid tumours75,77,78.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [75]
Critical telomere shortening (12.8 repeats) or loss of telomere-capping proteins results in telomere dysfunction with consequent chromosome fusion and genome instability.
“Critical telomere shortening (12.8 repeats of repetitive clusters) either as a loss of telomere-capping proteins results to telomere dysfunction with consequent chromosomes fusion and genome instability [22].”
From Markers of cellular senescence. Telomere shortening as a marker of cellular senescence (2016) · cites this paper as [22]
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Cites
Specific Association of Human Telomerase Activity with Immortal Cells and Cancer
Kim, N. W., Piatyszek, M. A., Prowse, K. R., Harley, C. B., West, M. D., Ho, P. L. C., Coviello, G. M., Wright, W. E., Weinrich, S. L., & Shay, J. W. (1994) · Science · doi:10.1126/science.7605428 · Cited by 7,091 · cited 2× · see citing works
“They occur early in tumor development, after which the genome appears to stabilize with advancing malignancy, roughly coincident with the activation of telomerase (Kim et al. 1994; Chadeneau et al. 1995; Meyerson et al. 1997).”
BackgroundTelomeres 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
Characteristics of a human cell line transformed by DNA from human adenovirus type 5
Graham, F. L., Russell, W. C., Smiley, J., & Nairn, R. (1977) · Journal of General Virology · doi:10.1099/0022-1317-36-1-59 · Cited by 4,793 · see citing works
Identification of a specific telomere terminal transferase activity in tetrahymena extracts
Greider, C. W., & Blackburn, E. H. (1985) · Cell · doi:10.1016/0092-8674(85)90170-9 · Cited by 3,400 · 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 Human Cell Line From a Pleural Effusion Derived From a Breast Carcinoma 2
Soule, H. D., Vázquez, J., Long, A., Albert, S. M., & BRENNAN, M. D. (1973) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/51.5.1409 · Cited by 2,452 · see citing works
Meyerson, M., Counter, C. M., Eaton, E. N., Ellisen, L. W., Steiner, P., Caddle, S. D., Ziaugra, L., Beijersbergen, R. L., Davidoff, M. J., Liu, Q., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80538-3 · Cited by 1,784 · 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
DNA Damage Foci at Dysfunctional Telomeres
Takai, H., Smogorzewska, A., & de Lange, T. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00542-6 · Cited by 1,409 · 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 2× · see citing works
“Late-generation telomerase knockout mice ( terc −/− ) show telomere loss, genomic instability, a higher rate of tumor formation, and a lower age of onset (Rudolph et al. 1999; O’Hagan et al. 2002).”
BackgroundHemann, 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
Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice
Artandi, S. E., Chang, S., Lee, S.-L., Alson, S., Gottlieb, G. J., Chin, L., & DePinho, R. A. (2000) · Nature · doi:10.1038/35020592 · Cited by 1,085 · 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
Human telomeres contain two distinct Myb–related proteins, TRF1 and TRF2
Broccoli, D., Smogorzewska, A., Chong, L., & de Lange, T. (1997) · Nature Genetics · doi:10.1038/ng1097-231 · Cited by 926 · see citing works
Chong, L., van Steensel, B., Broccoli, D., Erdjument‐Bromage, H., Hanish, J., Tempst, P., & de Lange, T. (1995) · Science · doi:10.1126/science.270.5242.1663 · Cited by 692 · 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
Characteristics of a Human Diploid Cell Designated MRC-5
JACOBS, J. P., JONES, C. M., & BAILLE, J. P. (1970) · Nature · doi:10.1038/227168a0 · Cited by 610 · see citing works
Extensive allelic variation and ultrashort telomeres in senescent human cells
Baird, D. M., Rowson, J., Wynford-Thomas, D., & Kipling, D. (2003) · Nature Genetics · doi:10.1038/ng1084 · Cited by 570 · see citing works
Self-citation[Principle of marginotomy in template synthesis of polynucleotides].
Olovnikov, A. M. (1971) · PubMed · Cited by 567 · see citing works
Telomere dysfunction and evolution of intestinal carcinoma in mice and humans
Rudolph, K. L., Millard, M., Bosenberg, M. W., & DePinho, R. A. (2001) · Nature Genetics · doi:10.1038/88871 · Cited by 527 · see citing works
Boulton, S. J., & Jackson, S. P. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00890.x · Cited by 502 · see citing works
Gisselsson, D., Jonson, T., Petersén, Å., Strömbeck, B., Cin, P. D., Höglund, M., Mitelman, F., Mertens, F., & Mandahl, N. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211357798 · Cited by 416 · see citing works
Expression of TERT in early premalignant lesions and a subset of cells in normal tissues
Kolquist, K. A., Ellisen, L. W., Counter, C. M., Meyerson, M. M., Tan, L. K., Weinberg, R. A., Haber, D. A., & Gerald, W. L. (1998) · Nature Genetics · doi:10.1038/554 · Cited by 382 · see citing works
Evidence that genetic instability occurs at an early stage of colorectal tumorigenesis.
Shih, I., Zhou, W. J., Goodman, S. N., Christoph Lengauer, C., Kinzler, K. W., & Vogelstein, B. (2001) · PubMed · Cited by 381 · see citing works
DNA Ligase IV-Dependent NHEJ of Deprotected Mammalian Telomeres in G1 and G2
Smogorzewska, A., Karlseder, J., Holtgreve-Grez, H., Jauch, A. S., & de Lange, T. (2002) · Current Biology · doi:10.1016/s0960-9822(02)01179-x · Cited by 377 · see citing works
Characterization of a New Human Diploid Cell Strain, IMR-90
Nichols, W. W., Murphy, D. G., Cristofalo, V. J., Toji, L. H., Greene, A. E., & Dwight, S. (1977) · Science · doi:10.1126/science.841339 · Cited by 368 · see citing works
Ma, N. J.-L., Kim, E. M., Haber, J. E., & Lee, S. E. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.23.8820-8828.2003 · Cited by 366 · see citing works
Maringele, L., & Lydall, D. A. (2002) · Genes & Development · doi:10.1101/gad.225102 · Cited by 300 · see citing works
d'Adda di Fagagna, F., Hande, M. P., Tong, W.-M., Roth, D., Lansdorp, P. M., Wang, Z.-Q., & Jackson, S. P. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00328-1 · Cited by 293 · see citing works
Human papillomavirus types 16 and 18 sequences in carcinoma cell lines of the cervix
Pater, M. M., & Pater, A. (1985) · Virology · doi:10.1016/0042-6822(85)90164-3 · Cited by 271 · see citing works
Properties of a non‐tumorigenic human cervical keratinocyte cell line
Stanley, M., Browne, H. M., Appleby, M. W., & Minson, A. C. (1989) · International Journal of Cancer · doi:10.1002/ijc.2910430422 · Cited by 268 · see citing works
Strand-Specific Postreplicative Processing of Mammalian Telomeres
Bailey, S. M., Cornforth, M. N., Kurimasa, A., Chen, D. J., & Goodwin, E. H. (2001) · Science · doi:10.1126/science.1062560 · Cited by 257 · see citing works
Pattillo, R. A., Hussa, R. O., Story, M. T., RUCKERT, A. C. F., Shalaby, M. R., & Mattingly, R. F. (1977) · Science · doi:10.1126/science.867042 · Cited by 254 · see citing works
Telomere dysfunction provokes regional amplification and deletion in cancer genomes
O'Hagan, R. C., Chang, S., Maser, R. S., Mohan, R., Artandi, S. E., Chin, L., & DePinho, R. A. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00094-6 · Cited by 246 · see citing works
Feldmann, E., Schmiemann, V., Goedecke, W., Reichenberger, S., & Pfeiffer, P. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.13.2585 · Cited by 235 · 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
Pett, M. R., Alazawi, W., Roberts, I., Dowen, S. E., Smith, D. I., Stanley, M., & Coleman, N. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3214 · Cited by 204 · see citing works
Friedl, F., Kimura, I., Õsato, T., & Ito, Y. (1970) · Experimental Biology and Medicine · doi:10.3181/00379727-135-35091a · Cited by 204 · see citing works
Shay, J. W., Wright, W. E., Brasiskyte, D., & Haegen, B. A. (1993) · PubMed · Cited by 201 · see citing works
A mechanistic basis for Mre11-directed DNA joining at microhomologies
Paull, T. T., & Gellert, M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.110144297 · Cited by 188 · see citing works
Molecular analysis of telomere fusions in Arabidopsis: multiple pathways for chromosome end‐joining
Heacock, M. L., Spangler, E. A., Říha, K., Puizina, J., & Shippen, D. E. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600236 · Cited by 188 · see citing works
Moreau, S., Morgan, E. A., & Symington, L. S. (2001) · Genetics · doi:10.1093/genetics/159.4.1423 · Cited by 176 · see citing works
Protection of Telomeres by the Ku Protein in Fission Yeast
Baumann, P., & Cech, T. R. (2000) · Molecular Biology of the Cell · doi:10.1091/mbc.11.10.3265 · Cited by 168 · see citing works
(1971) · PubMed · Cited by 157 · see citing works
Telomere instability in the male germline
Baird, D. M., Britt‐Compton, B., Rowson, J., Amso, N. N., Gregory, L., & Kipling, D. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi424 · Cited by 152 · see citing works
Self-citationClinical significance of cytogenetic findings in solid tumors
Mitelman, F., Johansson, B., Mandahl, N., & Mertens, F. (1997) · Cancer Genetics and Cytogenetics · doi:10.1016/s0165-4608(96)00252-x · Cited by 138 · see citing works
Telomerase activity in normal and malignant murine tissues.
Chadéneau, C., Siegel, P. M., Cb, H., Wj, M., & Bacchetti, S. (1995) · PubMed · Cited by 127 · see citing works
Britt‐Compton, B., Rowson, J., Locke, M., Mackenzie, I. M., Kipling, D., & Baird, D. M. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddi486 · Cited by 125 · see citing works
Self-citationBaird, D. M., Jeffreys, A. J., & Royle, N. J. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00227.x · Cited by 116 · see citing works
Self-citationLong-Term Cultivation of Hypodiploid Human Tumor Cells 2 3
Auersperg, N. (1964) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/32.1.135 · Cited by 110 · see citing works
Bond, J. A., Haughton, M. F., Rowson, J. M., Smith, P. J., Gire, V., Wynford-Thomas, D., & Wyllie, F. S. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.4.3103 · Cited by 104 · see citing works
Self-citationTelomere Length Dynamics in Telomerase-Positive Immortal Human Cell Populations
Bryan, T. M., Englezou, A., Dunham, M. A., & Reddel, R. R. (1998) · Experimental Cell Research · doi:10.1006/excr.1997.3907 · Cited by 104 · see citing works
End Resection Initiates Genomic Instability in the Absence of Telomerase
Hackett, J. A., & Greider, C. W. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.23.8450-8461.2003 · Cited by 103 · see citing works
Rejoining of DNA double‐strand breaks in vitro by single‐strand annealing
Göttlich, B., Reichenberger, S., Feldmann, E., & Pfeiffer, P. (1998) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1998.2580387.x · Cited by 100 · see citing works
Yu, X., & Gabriel, A. (2003) · Genetics · doi:10.1093/genetics/163.3.843 · Cited by 89 · see citing works
Telomerase activity in gynecological tumors.
Kyo, S., Kanaya, T., Ishikawa, H., Ueno, H., & Inoue, M. (1996) · PubMed · Cited by 86 · see citing works
Lei, M., Baumann, P., & Cech, T. R. (2002) · Biochemistry · doi:10.1021/bi026674z · Cited by 82 · see citing works
Maser, R. S., Wong, K., Sahin, E., Xia, H., Naylor, M. L., Hedberg, H. M., Artandi, S. E., & DePinho, R. A. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01354-06 · Cited by 79 · see citing works
Gisselsson, D., Gorunova, L., Höglund, M., Mandahl, N., & Elfving, P. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6601803 · Cited by 33 · see citing works
Lack of reciprocal translocations in carcinomas
Atkin, N. B. (1986) · Cancer Genetics and Cytogenetics · doi:10.1016/0165-4608(86)90009-9 · Cited by 31 · see citing works
FEDOROFF, S. (1971) · PubMed · Cited by 8 · see citing works
Flagged first, then by citations
1 of the 62 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
How Shelterin Protects Mammalian Telomeres
Palm, W., & de Lange, T. (2008) · Annual Review of Genetics · doi:10.1146/annurev.genet.41.110306.130350 · Cited by 1,802 · see citing works
Living on a break: cellular senescence as a DNA-damage response
d'Adda di Fagagna, F. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2440 · Cited by 1,170 · see citing works
Telomeres in cancer: tumour suppression and genome instability
Maciejowski, J., & de Lange, T. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.171 · Cited by 745 · see citing works
Mammalian polymerase θ promotes alternative NHEJ and suppresses recombination
Mateos‐Gómez, P. A., Gong, F., Nair, N., Miller, K. M., Denchi, E. L., & Sfeir, A. J. (2015) · Nature · doi:10.1038/nature14157 · Cited by 758 · see citing works
Chromothripsis and Kataegis Induced by Telomere Crisis
Maciejowski, J., Li, Y., Bosco, N., Campbell, P. J., & de Lange, T. (2015) · Cell · doi:10.1016/j.cell.2015.11.054 · Cited by 675 · see citing works
Mechanisms of Dysfunction in the Aging Vasculature and Role in Age-Related Disease
Donato, A. J., Machin, D. R., & Lesniewski, L. A. (2018) · Circulation Research · doi:10.1161/circresaha.118.312563 · Cited by 699 · 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
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
Williams, R. H., Khan, I. M., Richardson, K., Nelson, L., McCarthy, H. E., Analbelsi, T., Singhrao, S. K., Dowthwaite, G. P., Jones, R. E., Baird, D. M., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013246 · Cited by 406 · see citing works
Self-citationShortened Telomere Length Is Associated with Increased Risk of Cancer: A Meta-Analysis
Ma, H., Zhou, Z., Wei, S., Liu, Z., Pooley, K. A., Dunning, A. M., Svenson, U., Roos, G., Hosgood, H. D., Shen, M., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020466 · Cited by 376 · see citing works
“break, causing genome instability and enhancing potential for malignant transformation via fusion-bridge-breakage cycles [56].”
Stepanenko, A. A., & Dmitrenko, V. V. (2015) · Gene · doi:10.1016/j.gene.2015.05.065 · Cited by 324 · see citing works
Two subsets of stem-like CD8+ memory T cell progenitors with distinct fate commitments in humans
Galletti, G., De Simone, G., Mazza, E. M. C., Puccio, S., Mezzanotte, C., Bi, T. M., Davydov, A. N., Metsger, M., Scamardella, E., Alvisi, G., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0791-5 · Cited by 299 · see citing works
Self-citationERCC1-XPF Endonuclease Facilitates DNA Double-Strand Break Repair
Ahmad, A., Robinson, A. R., Duensing, A. U., van Drunen, E., Beverloo, H. B., Weisberg, D. B., Hasty, P., Hoeijmakers, J. H. J., & Niedernhofer, L. J. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.00293-08 · Cited by 298 · see citing works
Boonekamp, J. J., Mulder, G., Salomons, H. M., Dijkstra, C., & Verhulst, S. (2014) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2013.3287 · Cited by 289 · see citing works
Chiba, K., Lorbeer, F. K., Shain, A. H., McSwiggen, D. T., Schruf, E., Oh, A., Ryu, J., Darzacq, X., Bastian, B. C., & Hockemeyer, D. F. (2017) · Science · doi:10.1126/science.aao0535 · Cited by 276 · see citing works
Telomere shortening and survival in free-living corvids
Salomons, H. M., Mulder, G. A., van de Zande, L., Haussmann, M. F., Linskens, M. H. K., & Verhulst, S. (2009) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2009.0517 · Cited by 257 · see citing works
Microhomology-mediated end joining: Good, bad and ugly
Seol, J.-H., Shim, E. Y., & Lee, S. E. (2017) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2017.07.002 · Cited by 249 · see citing works
Frequent loss of heterozygosity in CRISPR-Cas9–edited early human embryos
Alanis-Lobato, G., Zohren, J., McCarthy, A., Fogarty, N. M. E., Kubikova, N., Hardman, E., Greco, M., Wells, D., Turner, J. M. A., & Niakan, K. K. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2004832117 · Cited by 234 · see citing works
Telomere dysfunction and chromosome instability
Murnane, J. P. (2011) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2011.04.008 · Cited by 230 · see citing works
Complex interactions between the DNA-damage response and mammalian telomeres
Arnoult, N., & Karlseder, J. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3092 · Cited by 202 · see citing works
Telomeres: Linking stress and survival, ecology and evolution
Haussmann, M. F., & Marchetto, N. M. (2010) · Current Zoology · doi:10.1093/czoolo/56.6.714 · Cited by 193 · see citing works
Rai, R., Zheng, H., He, H., Luo, Y., Multani, A. S., Carpenter, P. B., & Chang, S. S. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.142 · Cited by 190 · see citing works
DNA damage response at functional and dysfunctional telomeresPreprint
Longhese, M. P. (2008) · Genes & Development · doi:10.1101/gad.1626908 · Cited by 180 · see citing works
Lin, T. T., Letsolo, B. T., Jones, R. E., Rowson, J., Pratt, G., Hewamana, S., Fegan, C., Pepper, C., & Baird, D. M. (2010) · Blood · doi:10.1182/blood-2010-02-272104 · Cited by 178 · see citing works
Self-citationA Prospective Study of Telomere Length and the Risk of Skin Cancer
Han, J., Qureshi, A. A., Prescott, J., Guo, Q., Ye, L., Hunter, D. J., & Vivo, I. D. (2008) · Journal of Investigative Dermatology · doi:10.1038/jid.2008.238 · Cited by 173 · see citing works
Stop pulling my strings — what telomeres taught us about the DNA damage response
Denchi, E. L., & Sfeir, A. J. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.43 · Cited by 166 · see citing works
Alternative end-joining pathway(s): Bricolage at DNA breaks
Frit, P., Barboule, N., Yuan, Y., Gómez, D., & Calsou, P. (2014) · DNA repair · doi:10.1016/j.dnarep.2014.02.007 · Cited by 166 · see citing works
The evolution of senescence from a comparative perspective
Ricklefs, R. E. (2008) · Functional Ecology · doi:10.1111/j.1365-2435.2008.01420.x · Cited by 165 · see citing works
The Role of Telomere Biology in Cancer
Xu, L., Li, S., & Stohr, B. A. (2013) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-020712-164030 · Cited by 160 · see citing works
Mechanisms of telomere loss and their consequences for chromosome instability
Muraki, K., Nyhan, K. C., Han, L., & Murnane, J. P. (2012) · Frontiers in Oncology · doi:10.3389/fonc.2012.00135 · Cited by 162 · see citing works
Human RAP1 inhibits non‐homologous end joining at telomeres
Sarthy, J., Bae, N. S., Scrafford, J., & Baumann, P. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.275 · Cited by 151 · see citing works
Alternative end-joining mechanisms: a historical perspective
Decottignies, A. (2013) · Frontiers in Genetics · doi:10.3389/fgene.2013.00048 · Cited by 140 · see citing works
Gavia-García, G., Rosado-Pérez, J., Arista-Ugalde, T. L., Aguíñiga-Sánchez, I., Santiago‐Osorio, E., & Mendoza-Núñez, V. M. (2021) · Biology · doi:10.3390/biology10040253 · Cited by 141 · see citing works
DNA repair defects and genome instability in Hutchinson–Gilford Progeria Syndrome
Gonzalo, S., & Kreienkamp, R. J. (2015) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2015.05.007 · Cited by 134 · see citing works
Mancini, A., Xavier‐Magalhães, A., Woods, W. S., Nguyen, K.-T., Amen, A. M., Hayes, J. L., Fellmann, C., Gapinske, M., McKinney, A., Hong, C., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.08.003 · Cited by 134 · see citing works
Blood Cell Telomere Length Is a Dynamic Feature
Svenson, U., Nordfjäll, K., Baird, D., Roger, L., Osterman, P., Hellenius, M.-L., & Roos, G. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021485 · Cited by 132 · see citing works
Self-citationHuman Telomere Structure and Biology
Riethman, H. C. (2008) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.8.021506.172017 · Cited by 125 · see citing works
Telomeres and telomerase in prostate cancer development and therapy
Graham, M. K., & Meeker, A. K. (2017) · Nature Reviews Urology · doi:10.1038/nrurol.2017.104 · Cited by 122 · see citing works
Chronic toxicology of cannabis
Reece, A. S. (2009) · Clinical Toxicology · doi:10.1080/15563650903074507 · Cited by 118 · see citing works
Variation at theTERTlocus and predisposition for cancer
Baird, D. M. (2010) · Expert Reviews in Molecular Medicine · doi:10.1017/s146239941000147x · Cited by 115 · see citing works
Self-citationSizing the ends: Normal length of human telomeres
Samassékou, O., Gadji, M., Drouin, R., & Yan, J. (2010) · Annals of Anatomy - Anatomischer Anzeiger · doi:10.1016/j.aanat.2010.07.005 · Cited by 115 · see citing works
Chromosomally integrated HHV-6: impact on virus, cell and organismal biology
Kaufer, B. B., & Flamand, L. (2014) · Current Opinion in Virology · doi:10.1016/j.coviro.2014.09.010 · Cited by 109 · see citing works
Telomeres shorten more slowly in slow-aging wild animals than in fast-aging ones
Dantzer, B., & Fletcher, Q. E. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.08.012 · Cited by 102 · see citing works
Ohno, Y., Ogiyama, Y., Kubota, Y., Kubo, T., & Ishii, K. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv997 · Cited by 102 · see citing works
Gravel, A., Dubuc, I., Morissette, G., Sedlak, R. H., Jerome, K. R., & Flamand, L. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1502741112 · Cited by 98 · see citing works
CCR8 Expression Defines Tissue-Resident Memory T Cells in Human Skin
McCully, M. L., Ladell, K., Andrews, R., Jones, R. E., Miners, K. L., Roger, L., Baird, D. M., Cameron, M. J., Jessop, Z. M., Whitaker, I. S., et al. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701377 · Cited by 99 · see citing works
Self-citationLi, X., Liu, J., Zhou, G., Sang, Y., Zhang, Y., Li, J., Shi, Z., Zhou, X., & Sun, Z. (2020) · Environment International · doi:10.1016/j.envint.2020.106307 · Cited by 98 · see citing works
Roger, L., Jones, R. E., Heppel, N. H., Williams, G. T., Sampson, J. R., & Baird, D. M. (2013) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djt191 · Cited by 97 · see citing works
Self-citationTelomeres, aging, and cancer: the big picture
Lansdorp, P. M. (2022) · Blood · doi:10.1182/blood.2021014299 · Cited by 95 · see citing works
Letsolo, B. T., Rowson, J., & Baird, D. M. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp1183 · Cited by 95 · see citing works
Self-citationBurraco, P., Díaz‐Paniagua, C., & Gómez-Mestre, I. (2017) · Scientific Reports · doi:10.1038/s41598-017-07201-z · Cited by 94 · see citing works
Lin, T. T., Norris, K., Heppel, N. H., Pratt, G., Allan, J. M., Allsup, D. J., Bailey, J. R., Cawkwell, L., Hills, R. K., Grimstead, J. W., et al. (2014) · British Journal of Haematology · doi:10.1111/bjh.13023 · Cited by 92 · see citing works
Self-citationFellows, C. R., Williams, R., Davies, I. R., Gohil, K., Baird, D. M., Fairclough, J. A., Rooney, P., Archer, C. W., & Khan, I. M. (2017) · Scientific Reports · doi:10.1038/srep41421 · Cited by 92 · see citing works
Self-citationTelomerase in Cancer: Function, Regulation, and Clinical Translation
Robinson, N. J., & Schiemann, W. P. (2022) · Cancers · doi:10.3390/cancers14030808 · Cited by 94 · see citing works
Platt, J. M., Ryvkin, P., Wanat, J. J., Donahue, G., Ricketts, M. D., Barrett, S. P., Waters, H. J., Song, S., Chavez, A., Abdallah, K. O., et al. (2013) · Genes & Development · doi:10.1101/gad.218776.113 · Cited by 89 · see citing works
Repeated stressors in adulthood increase the rate of biological ageing
Hau, M., Haussmann, M. F., Greives, T. J., Matlack, C., Costantini, D., Quetting, M., Adelman, J. S., Miranda, A. C., & Partecke, J. (2015) · Frontiers in Zoology · doi:10.1186/s12983-015-0095-z · Cited by 85 · see citing works
Comparative biology of telomeres: Where plants stand
Watson, J. M., & Říha, K. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.06.017 · Cited by 83 · see citing works
Whole chromosome loss is promoted by telomere dysfunction in primary cells
Pampalona, J., Soler, D., Genescà, A., & Tusell, L. (2010) · Genes Chromosomes and Cancer · doi:10.1002/gcc.20749 · Cited by 82 · see citing works
Human Stem Cell-like Memory T Cells Are Maintained in a State of Dynamic Flux
Ahmed, R., Roger, L., del Amo, P. C., Miners, K. L., Jones, R. E., Boelen, L., Fali, T., Elemans, M., Zhang, Y., Appay, V., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.11.037 · Cited by 82 · see citing works
Self-citationElevated levels of TRF2 induce telomeric ultrafine anaphase bridges and rapid telomere deletions
Nera, B., Huang, H.-S., Lai, T., & Xu, L. (2015) · Nature Communications · doi:10.1038/ncomms10132 · Cited by 79 · see citing works
High resolution long-read telomere sequencing reveals dynamic mechanisms in aging and cancer
Schmidt, T. T., Tyer, C., Rughani, P., Haggblom, C., Jones, J. R., Dai, X., Frazer, K. A., Gage, F. H., Juul, S., Hickey, S. F., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48917-7 · Cited by 79 · see citing works
Chromosomal aberrations involving telomeres and interstitial telomeric sequences
Bolzán, A. D. (2011) · Mutagenesis · doi:10.1093/mutage/ger052 · Cited by 77 · see citing works
Salivary Gland Stem Cells Age Prematurely in Primary Sjögren's Syndrome
Pringle, S. A., Wang, X., Verstappen, G. M. P. J., Terpstra, J. H., Zhang, H., He, A., Patel, V. N., Jones, R. E., Baird, D. M., Spijkervet, F. K. L., et al. (2018) · Arthritis & Rheumatology · doi:10.1002/art.40659 · Cited by 79 · see citing works
Self-citationHuman TSCM cell dynamics in vivo are compatible with long-lived immunological memory and stemness
del Amo, P. C., Lahoz-Beneytez, J., Boelen, L., Ahmed, R., Miners, K. L., Zhang, Y., Roger, L., Jones, R. E., Marraco, S. A. F., Speiser, D. E., et al. (2018) · PLoS Biology · doi:10.1371/journal.pbio.2005523 · Cited by 74 · see citing works
Self-citationEscape from Telomere-Driven Crisis Is DNA Ligase III Dependent
Jones, R. E., Oh, S., Grimstead, J. W., Zimbric, J., Roger, L., Heppel, N. H., Ashelford, K. E., Liddiard, K., Hendrickson, E. A., & Baird, D. M. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.07.007 · Cited by 74 · see citing works
Self-citationHuman RAP1 specifically protects telomeres of senescent cells from DNA damage
Lototska, L., Yue, J., Li, J., Giraud-Panis, M.-J. E., Songyang, Z., Royle, N. J., Liti, G., Ye, J., Gilson, É., & Méndez-Bermúdez, A. (2020) · EMBO Reports · doi:10.15252/embr.201949076 · Cited by 74 · see citing works
Telomere Dysfunction and DNA-PKcs Deficiency: Characterization and Consequence
Williams, E. S., Klingler, R., Ponnaiya, B., Hardt, T., Schröck, E., Lees‐Miller, S. P., Meek, K., Ullrich, R. L., & Bailey, S. M. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2854 · Cited by 73 · see citing works
Diet-related telomere shortening and chromosome stability
Marcon, F., Siniscalchi, E., Crebelli, R., Saieva, C., Sera, F., Fortini, P., Simonelli, V., & Palli, D. (2011) · Mutagenesis · doi:10.1093/mutage/ger056 · Cited by 71 · see citing works
Telomere Length Dynamics and the Evolution of Cancer Genome Architecture
Cleal, K., Norris, K., & Baird, D. M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19020482 · Cited by 71 · see citing works
Self-citationTelomeres and Cancer: Resolving the Paradox
Nassour, J., Schmidt, T. T., & Karlseder, J. (2021) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-050420-023410 · Cited by 64 · see citing works
Short telomeres are preferentially elongated by telomerase in human cells
Britt‐Compton, B., Capper, R., Rowson, J., & Baird, D. M. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.08.029 · Cited by 62 · see citing works
Self-citationUPF1 promotes the formation of R loops to stimulate DNA double-strand break repair
Ngo, H.-P., Grimstead, J. W., & Baird, D. M. (2021) · Nature Communications · doi:10.1038/s41467-021-24201-w · Cited by 61 · see citing works
Self-citationTelomere dysfunction and genome instability
Frías-López, C. (2012) · Frontiers in bioscience · doi:10.2741/4044 · Cited by 62 · see citing works
Telomere dysfunction and its role in haematological cancer
Jones, C. H., Pepper, C. J., & Baird, D. M. (2012) · British Journal of Haematology · doi:10.1111/j.1365-2141.2011.09022.x · Cited by 60 · see citing works
Self-citationHuman Rap1 Interacts Directly with Telomeric DNA and Regulates TRF2 Localization at the Telomere
Arat, N. Ö., & Griffith, J. D. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.415984 · Cited by 60 · see citing works
Give me a break: How telomeres suppress the DNA damage response
Denchi, E. L. (2009) · DNA repair · doi:10.1016/j.dnarep.2009.04.013 · Cited by 57 · see citing works
MacKinnon, R. N., & Campbell, L. J. (2011) · Genetics Research International · doi:10.4061/2011/643628 · Cited by 56 · see citing works
Bauch, C., Becker, P. H., & Verhulst, S. (2013) · Molecular Ecology · doi:10.1111/mec.12602 · Cited by 55 · see citing works
Taming the tiger by the tail: modulation of DNA damage responses by telomeres
Lydall, D. A. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.176 · Cited by 55 · see citing works
Telomere function and regulation from mouse models to human ageing and disease
Jones-Weinert, C. W., Mainz, L., & Karlseder, J. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00800-5 · Cited by 57 · see citing works
Structural identity of telomeric complexes
Giraud-Panis, M.-J. E., Pisano, S., Poulet, A., Du, M. L., & Gilson, É. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.08.004 · Cited by 54 · see citing works
Catastrophic Endgames: Emerging Mechanisms of Telomere-Driven Genomic Instability
Cleal, K., & Baird, D. M. (2020) · Trends in Genetics · doi:10.1016/j.tig.2020.02.001 · Cited by 52 · see citing works
Self-citationHuman subtelomeric copy number variations
Riethman, H. C. (2008) · Cytogenetic and Genome Research · doi:10.1159/000184714 · Cited by 50 · see citing works
Telomeres and genomic evolution
Baird, D. M. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0437 · Cited by 48 · see citing works
Self-citationDicentric breakage at telomere fusionsPreprint
Pobiega, S., & Marcand, S. (2010) · Genes & Development · doi:10.1101/gad.571510 · Cited by 46 · see citing works
DNA Synthesis Generates Terminal Duplications That Seal End-to-End Chromosome Fusions
Lowden, M. R., Flibotte, S., Moerman, D. G., & Ahmed, S. C. (2011) · Science · doi:10.1126/science.1199022 · Cited by 49 · see citing works
Gilbert-Girard, S., Gravel, A., Artusi, S., Richter, S. N., Wallaschek, N., Kaufer, B. B., & Flamand, L. (2017) · Journal of Virology · doi:10.1128/jvi.00402-17 · Cited by 47 · see citing works
Jovanovic, K., Chetty, C. J., Khumalo, T., Dias, B. D. C., Ferreira, E., Malindisa, S. T., Caveney, R. J., Letsolo, B. T., & Weiss, S. F. T. (2015) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.2015.1014802 · Cited by 47 · see citing works
Self-citationHigh-throughput single-molecule telomere characterizationPreprint
McCaffrey, J., YOUNG, E. A., Lassahn, K. A., Sibert, J. G., Pastor, S. J., Riethman, H. C., & Xiao, M. (2017) · Genome Research · doi:10.1101/gr.222422.117 · Cited by 48 · see citing works
Liddiard, K., Ruis, B. L., Takasugi, T., Harvey, A., Ashelford, K. E., Hendrickson, E. A., & Baird, D. M. (2016) · Genome Research · doi:10.1101/gr.200840.115 · Cited by 47 · see citing works
Self-citationTelomere fusion threshold identifies a poor prognostic subset of breast cancer patients
Simpson, K., Jones, R. E., Grimstead, J. W., Hills, R., Pepper, C., & Baird, D. M. (2015) · Molecular Oncology · doi:10.1016/j.molonc.2015.02.003 · Cited by 46 · see citing works
Self-citationOh, S., Wang, Y., Zimbric, J., & Hendrickson, E. A. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1326 · Cited by 46 · see citing works
Changes of telomere status with aging: An update
Ishikawa, N., Nakamura, K., Izumiyama‐Shimomura, N., Aida, J., Matsuda, Y., Arai, T., & Takubo, K. (2016) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/ggi.12772 · Cited by 44 · see citing works
CD57+ Memory T Cells Proliferate In Vivo
Ahmed, R., Miners, K. L., Lahoz-Beneytez, J., Jones, R. E., Roger, L., BABOONIAN, C., Zhang, Y., Wang, E. C. Y., Hellerstein, M. K., McCune, J. M., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108501 · Cited by 43 · see citing works
Self-citationLiu, S.-C., Feng, Y.-L., Sun, X., Chen, R.-D., Liu, Q., Xiao, J., Zhang, J., Huang, Z., Xiang, J.-F., Chen, G., et al. (2022) · Genome biology · doi:10.1186/s13059-022-02736-5 · Cited by 42 · see citing works
Genome stability from the perspective of telomere length
Lu, X., & Liu, L. (2023) · Trends in Genetics · doi:10.1016/j.tig.2023.10.013 · Cited by 41 · see citing works
Lundberg, G., Sehic, D., Länsberg, J., Øra, I., Frigyesi, A., Castel, V., Navarro, S., Piqueras, M., Martinsson, T., Noguera, R., et al. (2011) · Genes Chromosomes and Cancer · doi:10.1002/gcc.20850 · Cited by 41 · see citing works
Subtelomeric regions in mammalian cells are deficient in DNA double-strand break repair
Miller, D. L., Reynolds, G. E., Mejı́a, R., Stark, J. M., & Murnane, J. P. (2011) · DNA repair · doi:10.1016/j.dnarep.2011.03.001 · Cited by 41 · see citing works
Chen, C., Chang, D., Chen, T., Lee, C.-C., Hsieh, H.-H., Huang, F.-C., Huang, K.-F., Guh, J., Lin, J., & Huang, H. (2012) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2012.11.032 · Cited by 39 · see citing works
Mechanisms of telomeric instability
Baird, D. M. (2008) · Cytogenetic and Genome Research · doi:10.1159/000167817 · Cited by 40 · see citing works
Self-citation
- Authors
- Capper, R., Britt-Compton, B., Tankimanova, M., Rowson, J., Letsolo, B., Man, S., Haughton, M., & Baird, D. M.
- Affiliations
- Cardiff University (GB)
- Corresponding author
- Baird, Duncan M.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2007-10-01
- Volume
- 21
- Issue
- 19
- Pages
- 2495-2508
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC1993879
- OpenAlex
- W2159349156
- Cited by
- 294
- References
- 62
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 17 · 2023: 11 · 2022: 18 · 2021: 19 · 2020: 14 · 2019: 8 · 2018: 22 · 2017: 21 · 2016: 16 · 2015: 19 · 2014: 14 · 2013: 13 · 2012: 14
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- Funders
- Cancer Research UK
- Medical Research Council
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- telomere fusion, telomere shortening, chromosomal instability, non-reciprocal translocation, microhomology-mediated end joining, TRF2, telomerase, carcinogenesis, single-molecule analysis
- MeSH terms
- Base Sequence, Humans, Molecular Sequence Data, Mutagenesis, Insertional, Telomere, Cellular Senescence, Sequence Deletion, Tandem Repeat Sequences, Telomeric Repeat Binding Protein 2, Chromosomal Instability, Cell Line, Tumor
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