Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation
Abstract
Telomeres are specialized nucleoprotein complexes that serve as protective caps of linear eukaryotic chromosomes. Loss of telomere function is associated with rampant genetic instability and loss of cellular viability and renewal potential. The telomere also participates in processes of chromosomal repair, as evidenced by the 'capture' or de novo synthesis of telomere repeats at double-stranded breaks and by the capacity of yeast telomeres to serve as repositories of essential components of the DNA repair machinery, particularly those involved in non-homologous end-joining (NHEJ). Here we used the telomerase-deficient mouse, null for the essential telomerase RNA gene (Terc), to assess the role of telomerase and telomere function on the cellular and organismal response to ionizing radiation. Although the loss of telomerase activity per se had no discernable impact on the response to ionizing radiation, the emergence of telomere dysfunction in late-generation Terc-/- mice imparted a radiosensitivity syndrome associated with accelerated mortality. On the cellular level, the gastrointestinal crypt stem cells and primary thymocytes showed increased rates of apoptosis, and mouse embryonic fibroblasts (MEFs) showed diminished dose-dependent clonogenic survival. The radiosensitivity of telomere dysfunctional cells correlated with delayed DNA break repair kinetics, persistent chromosomal breaks and cytogenetic profiles characterized by complex chromosomal aberrations and massive fragmentation. Our findings establish a intimate relationship between functionally intact telomeres and the genomic, cellular and organismal response to ionizing radiation.
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Late generation Terc-deficient mice have an uncharacterized DSB repair defect.
“Late generation Terc-deficient mice have an uncharacterized DSB repair defect (Wong et al., 2000”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as Wong et al., 2000
The severe degenerative tissue defects in late-generation telomerase-knockout mice are linked to impaired proliferation and increased apoptosis in cycling progenitor cells and to a self-renewal defect in tissue stem cells.
“The severe degenerative tissue defects in the late-generation telomerase-knockout mice appear linked to impaired proliferation and increased apoptosis in cycling progenitor cells and to a selfrenewal defect in tissue stem cells.”
From Telomeres and telomerase in cancer (2010) · cites this paper as [63]
Late-generation telomerase-knockout mice show a premature aging syndrome with hair graying, shortened survival, and impaired responses to acute and chronic stress.
“Late-generation telomerase-knockout mice exhibit a premature aging syndrome characterized by hair graying, shortened survival and impaired responses to acute and chronic stress (63,77).”
From Telomeres and telomerase in cancer (2010) · cites this paper as [63]
In mice, short telomeres reduce the threshold for disease from additional external or internal insults, including γ-irradiation and ER stress from misfolded proteins.
“Indeed, in mouse models, short telomeres have been shown to lower the disease threshold to other exogenous and endogeneous damage, such as γ-irradiation119 and endoplasmic reticulum stress due to protein misfolding97 (Fig. 5a).”
From The telomere syndromes (2012) · cites this paper as [119]
In mTERC-/- mouse cells, telomere dysfunction is a prominent trait that impairs DNA repair and enhances sensitivity to ionizing radiation.
“Recent data suggest that in mTERC ±/± mouse cells telomere dysfunction is a prominent trait that impairs DNA repair and enhances sensitivity to ionizing radiation (Wong et al., 2000).”
From A highly selective telomerase inhibitor limiting human cancer cell proliferation (2001) · cites this paper as Wong et al., 2000
Cites
Radiobiology for the Radiologist.
(1974) · Annals of Internal Medicine · doi:10.7326/0003-4819-80-3-438_1 · Cited by 3,498 · see citing works
Telomere 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
Self-citationStem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt
Potten, C. S., & Loeffler, M. (1990) · Development · doi:10.1242/dev.110.4.1001 · Cited by 1,793 · 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
Self-citationEssential 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
“We used the telomerase-deficient mouse, in which telomeres are eroded to a critically short length through serial Terc −/− intercrosses to produce successive generations (G1 Terc −/− through G6 Terc −/− ) of Terc −/− mic”
MethodSelf-citationChin, L., Artandi, S. E., Shen, Q., Tam, A., Lee, S.-L., Gottlieb, G. J., Greider, C. W., & DePinho, R. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80762-x · Cited by 979 · cited 1× · see citing works
“2 a , c ), along with evidence of telomere dysfunction (anaphase bridging) and elevated p53 expression (data not shown), consistent with previous observations that telomere dysfunction activates the p53 protei”
BackgroundSelf-citationA critical role for DNA end-joining proteins in both lymphogenesis and neurogenesis
Gao, Y., Sun, Y., Frank, K. M., Dikkes, P., Fujiwara, Y., Seidl, K. J., Sekiguchi, J. M., Rathbun, G. A., Swat, W., Wang, J., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81714-6 · Cited by 688 · see citing works
Self-citationHomology-directed repair is a major double-strand break repair pathway in mammalian cells
Liang, F., Han, M., Romanienko, P. J., & Jasin, M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.9.5172 · Cited by 649 · see citing works
Late embryonic lethality and impaired V (D)J recombination in mice lacking DNA ligase IV
Frank, K. M., Sekiguchi, J., Seidl, K. J., Swat, W., Rathbun, G. A., Cheng, H.-L., Davidson, L., Kangaloo, L., & Alt, F. W. (1998) · Nature · doi:10.1038/24172 · Cited by 594 · see citing works
Self-citationRelocalization of telomeric Ku and SIR proteins in response to DNA strand breaks in yeast
Martin, S. G., Laroche, T., Suka, N., Grunstein, M., & Gasser, S. M. (1999) · Cell · doi:10.1016/s0092-8674(00)80773-4 · Cited by 464 · see citing works
Li, Z., Otevrel, T., Gao, Y., Cheng, H.-L., Seed, B., Stamato, T. D., Taccioli, G. E., & Alt, F. W. (1995) · Cell · doi:10.1016/0092-8674(95)90135-3 · Cited by 458 · see citing works
Self-citationGrowth Retardation and Leaky SCID Phenotype of Ku70-Deficient Mice
Gu, Y., Seidl, K. J., Rathbun, G. A., Zhu, C., Manis, J. P., van der Stoep, N., Davidson, L., Cheng, H.-L., Sekiguchi, J., Frank, K. M., et al. (1997) · Immunity · doi:10.1016/s1074-7613(00)80386-6 · Cited by 451 · see citing works
Self-citationImpairment of V(D)J Recombination in Double-Strand Break Repair Mutants
Taccioli, G. E., Rathbun, G. A., Oltz, E. M., Stamato, T. D., Jeggo, P. A., & Alt, F. W. (1993) · Science · doi:10.1126/science.8469973 · Cited by 451 · see citing works
Self-citationA Targeted DNA-PKcs-Null Mutation Reveals DNA-PK-Independent Functions for KU in V(D)J Recombination
Gao, Y., Chaudhuri, J., Zhu, C., Davidson, L., Weaver, D. T., & Alt, F. W. (1998) · Immunity · doi:10.1016/s1074-7613(00)80619-6 · Cited by 432 · see citing works
Self-citationIdentification of a defect in DNA ligase IV in a radiosensitive leukaemia patient
Riballo, E., Critchlow, S. E., Teo, S., Doherty, A. J., Priestley, A., Broughton, B. C., Kysela, B. P., Beamish, H., Plowman, N. P., Arlett, C. F., et al. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80311-x · Cited by 400 · see citing works
Grawunder, U., Zimmer, D., Fugmann, S. D., Schwarz, K., & Lieber, M. R. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80147-1 · Cited by 367 · see citing works
Genetic Analysis of BRCA1 Function in a Defined Tumor Cell Line
Scully, R., Ganesan, S., Vlasakova, K., Chen, J., Socolovsky, M., & Livingston, D. M. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80238-5 · Cited by 359 · see citing works
Self-citationp53 is linked directly to homologous recombination processes via RAD51/RecA protein interaction.
Stürzbecher, H.-W., Donzelmann, B., Henning, W., Knippschild, U., & Buchhop, S. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00550.x · Cited by 340 · 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
Hesse, J. E., Lieber, M. R., Gellert, M. F., & Mizuuchi, K. (1987) · Cell · doi:10.1016/0092-8674(87)90615-5 · Cited by 331 · see citing works
Identification of Genes Involved in Repair of DNA Double-Strand Breaks in Mammalian Cells
Jeggo, P. A. (1998) · Radiation Research · doi:10.2307/3579810 · Cited by 283 · see citing works
Examining the Role of Paneth Cells in the Small Intestine by Lineage Ablation in Transgenic Mice
Garabedian, E. M., Roberts, L. J., McNevin, M. S., & Gordon, J. I. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.38.23729 · Cited by 279 · see citing works
Radiobiology for the Radiologist
Markoe, A. M. (1988) · American Journal of Clinical Oncology · doi:10.1097/00000421-198808000-00024 · Cited by 231 · see citing works
Telomere capture stabilizes chromosome breakage
Meltzer, P. S., Guan, X., & Trent, J. M. (1993) · Nature Genetics · doi:10.1038/ng0793-252 · Cited by 161 · see citing works
Chromosome healing in mouse embryonic stem cells
Sprung, C. N., Reynolds, G. E., Jasin, M., & Murnane, J. P. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.12.6781 · Cited by 102 · see citing works
Sir-Ku-itous Routes to Make Ends Meet
Haber, J. E. (1999) · Cell · doi:10.1016/s0092-8674(00)80795-3 · Cited by 71 · see citing works
Murnane, J. P., & Yu, L. ‐. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.2.977 · Cited by 63 · see citing works
Kiltie, A. E. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.14.2945 · Cited by 53 · see citing works
Regulation and Repair of Double-Strand DNA Breaks
Weaver, D. T. (1996) · Critical Reviews in Eukaryotic Gene Expression · doi:10.1615/critreveukargeneexpr.v6.i4.20 · Cited by 49 · see citing works
Telomeres and radiation-induced chromosome breakage
Shjepcevic, P., Natarajan, A. T., & Bryant, P. E. (1998) · Mutagenesis · doi:10.1093/mutage/13.1.45 · Cited by 27 · see citing works
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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
Genomic Instability and Aging-like Phenotype in the Absence of Mammalian SIRT6
Mostoslavsky, R., Chua, K. F., Lombard, D. B., Pang, W. W., Fischer, M. R., Gellon, L., Liu, P., Mostoslavsky, G., Franco, S., Murphy, M. M., et al. (2006) · Cell · doi:10.1016/j.cell.2005.11.044 · Cited by 1,637 · see citing works
Self-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
Armanios, M., & Blackburn, E. H. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3246 · Cited by 982 · see citing works
DNA Repair, Genome Stability, and Aging
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
Self-citationTelomeres and telomerase in cancer
Artandi, S. E., & DePinho, R. A. (2010) · Carcinogenesis · doi:10.1093/carcin/bgp268 · Cited by 823 · see citing works
Self-citationTelomerase and cancer therapeutics
Harley, C. B. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2275 · Cited by 728 · see citing works
Telomerase modulates Wnt signalling by association with target gene chromatin
Park, J.-I., Venteicher, A. S., Hong, J. Y., Choi, J., Jun, S., Shkreli, M., Chang, W., Meng, Z., Cheung, P., Ji, H., et al. (2009) · Nature · doi:10.1038/nature08137 · Cited by 707 · see citing works
Self-citationHallmarks 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
Telomere Dysfunction: A Potential Cancer Predisposition Factor
Wu, X., Amos, C. I., Zhu, Y., Zhao, H., Grossman, B. H., Shay, J. W., Luo, S., Hong, W. K., & Spitz, M. R. (2003) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djg011 · Cited by 488 · 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-citationA highly selective telomerase inhibitor limiting human cancer cell proliferation
Damm, K., Hemmann, U., Garin‐Chesa, P., Hauel, N., Kauffmann, I., Priepke, H., Niestroj, C., Daiber, C., Enenkel, B., Guilliard, B., et al. (2001) · The EMBO Journal · doi:10.1093/emboj/20.24.6958 · Cited by 422 · 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
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
The telomerase reverse transcriptase regulates chromatin state and DNA damage responses
Masutomi, K., Possemato, R., Wong, J. M. Y., Currier, J. L., Tóthová, Z., Manola, J. B., Ganesan, S., Lansdorp, P. M., Collins, K., & Hahn, W. C. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503095102 · Cited by 381 · see citing works
Self-citationTelomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing
Wong, K.-K., Maser, R. S., Bachoo, R. M., Menon, J., Carrasco, D. R., Gu, Y., Alt, F. W., & DePinho, R. A. (2003) · Nature · doi:10.1038/nature01385 · Cited by 375 · see citing works
Self-citationT cells and aging january 2002 update
Pawelec, G. (2002) · Frontiers in bioscience · doi:10.2741/a831 · Cited by 368 · see citing works
Natural and pharmacological regulation of telomerase
Mergny, J. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.4.839 · Cited by 351 · see citing works
A synthetic lethal siRNA screen identifying genes mediating sensitivity to a PARP inhibitor
Turner, N. C., Lord, C. J., Iorns, E. J., Brough, R., Swift, S., Elliott, R. J. R., Rayter, S., Tutt, A. N. J., & Ashworth, A. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.61 · Cited by 322 · see citing works
Syndromes of Telomere Shortening
Armanios, M. (2009) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-082908-150046 · Cited by 317 · see citing works
Chromosomal aberrations: formation, identification and distribution
Obe, G., Pfeiffer, P., Savage, J. R. K., Johannes, C., Goedecke, W., Jeppesen, P., Natarajan, A. T., Martínez‐López, W., Folle, G. A., & Drets, M. E. (2002) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(02)00076-3 · Cited by 309 · see citing works
FLASH Irradiation Spares Lung Progenitor Cells and Limits the Incidence of Radio-induced Senescence
Fouillade, C., Curras-Alonso, S., Giuranno, L., Quelennec, E., Heinrich, S., Bonnet-Boissinot, S., Beddok, A., Leboucher, S., Karakurt, H. U., Bohec, M., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1440 · Cited by 311 · 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
Accelerated senescence: An emerging role in tumor cell response to chemotherapy and radiation
Gewirtz, D. A., Holt, S. E., & Elmore, L. W. (2008) · Biochemical Pharmacology · doi:10.1016/j.bcp.2008.06.024 · Cited by 281 · 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
Haendeler, J., Hoffmann, J. U. R., Brandes, R. P., Zeiher, A. M., & Dimmeler, S. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.13.4598-4610.2003 · Cited by 266 · see citing works
hTERT associates with human telomeres and enhances genomic stability and DNA repair
Sharma, G. G., Gupta, A. K. D., Wang, H., Scherthan, H., Dhar, S., Gandhi, V. V., Iliakis, G. E., Shay, J. W., Young, C. S. H., & Pandita, T. K. (2003) · Oncogene · doi:10.1038/sj.onc.1206063 · Cited by 254 · see citing works
Targeting hallmarks of cancer to enhance radiosensitivity in gastrointestinal cancers
Buckley, A. M., Lynam‐Lennon, N., O’Neill, H., & O'Sullivan, J. N. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0247-2 · Cited by 255 · see citing works
Short Telomeres Result in Organismal Hypersensitivity to Ionizing Radiation in Mammals
Goytisolo, F. A., Samper, E., Martín‐Caballero, J., Finnon, P., Herrera, E., Flores, J. M., Bouffler, S. D., & Blasco, M. A. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.11.1625 · Cited by 223 · see citing works
Genomic Instability and Enhanced Radiosensitivity in Hsp70.1- and Hsp70.3-Deficient Mice
Hunt, C. R., Dix, D. J., Sharma, G. G., PANDITA, R. K., Gupta, A. K. D., Funk, M. C., & Pandita, T. K. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.24.2.899-911.2004 · Cited by 222 · see citing works
Telomere Shortening Exposes Functions for the Mouse Werner and Bloom Syndrome Genes
Du, X., Shen, J., Kugan, N., Furth, E. E., Lombard, D. B., Cheung, C., Pak, S., Luo, G., Pignolo, R. J., DePinho, R. A., et al. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.19.8437-8446.2004 · Cited by 213 · see citing works
Self-citationDNA damage checkpoint kinase Chk2 triggers replicative senescence
Gire, V., Roux, P., Wynford‐Thomas, D., Brondello, J., & Dulic, V. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600259 · Cited by 198 · see citing works
Stress, DNA damage and ageing — an integrative approach
von Zglinicki, T. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00111-5 · Cited by 200 · see citing works
Telomere attrition and Chk2 activation in human heart failure
Oh, H., Wang, S. C., Prahash, A. J. C., Sano, M., Moravec, C. S., Taffet, G. E., Michael, L. H., Youker, K. A., Entman, M. L., & Schneider, M. D. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0836098100 · Cited by 197 · see citing works
Harley, C. B. (2002) · Oncogene · doi:10.1038/sj.onc.1205076 · Cited by 193 · see citing works
Pathways connecting telomeres and p53 in senescence, apoptosis, and cancer
Artandi, S. E., & Attardi, L. D. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.03.211 · Cited by 190 · see citing works
Self-citationShort 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
Ergin, A., Muntner, P., Sherwin, R. W., & He, J. (2004) · The American Journal of Medicine · doi:10.1016/j.amjmed.2004.03.017 · Cited by 173 · 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
Genetic susceptibility to tobacco-related cancer
Wu, X., Zhao, H., Suk, R. N., & Christiani, D. C. (2004) · Oncogene · doi:10.1038/sj.onc.1207811 · Cited by 154 · 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
Djojosubroto, M. W., Chin, A. C., Go, N., Schaetzlein, S., Manns, M. P., Gryaznov, S., Harley, C. B., & Rudolph, L. K. (2005) · Hepatology · doi:10.1002/hep.20822 · Cited by 151 · see citing works
Self-citationMice with bad ends: mouse models for the study of telomeres and telomerase in cancer and aging
Blasco, M. A. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600598 · Cited by 147 · see citing works
TERT promotes cellular and organismal survival independently of telomerase activity
Lee, J., Sung, Y. H., Cheong, C., Choi, Y. S., Jeon, H. K., Sun, W., Hahn, W. C., Ishikawa, F., & Lee, H.-W. (2008) · Oncogene · doi:10.1038/sj.onc.1211037 · Cited by 145 · see citing works
Role of Telomeres and Telomerase in the Pathogenesis of Human Cancer
Hahn, W. C. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.06.018 · Cited by 141 · see citing works
Involvement of hTERT in apoptosis induced by interference with Bcl-2 expression and function
Bufalo, D. D., Rizzo, A., Trisciuoglio, D., Cardinali, G., Torrisi, M. R., Zangemeister‐Wittke, U., Zupi, G., & Biroccio, A. (2005) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401670 · Cited by 140 · see citing works
Strong, M. A., Vidal-Cardenas, S. L., Karim, B. O., Yu, H. M., Guo, N., & Greider, C. W. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05312-11 · Cited by 134 · see citing works
The XRCC genes: expanding roles in DNA double-strand break repair
Thacker, J., & Zdzienicka, M. Z. (2004) · DNA repair · doi:10.1016/j.dnarep.2004.04.012 · Cited by 135 · see citing works
Seimiya, H., Oh‐hara, T., Suzuki, T., Naasani, I., Shimazaki, T., Tsuchiya, K., & Tsuruo, T. (2002) · PubMed · Cited by 133 · see citing works
PANDITA, R. K., Sharma, G. G., Laszlo, A., Hopkins, K. M., Davey, S. K., Chakhparonian, M., Gupta, A. K. D., Wellinger, R. J., Zhang, J., Powell, S. N., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.5.1850-1864.2006 · Cited by 129 · see citing works
Short telomere syndromes cause a primary T cell immunodeficiency
Wagner, C. L., Hanumanthu, V. S., Talbot, C. C., Abraham, R. S., Hamm, D. E., Gable, D. L., Kanakry, C. G., Applegate, C. D., Siliciano, J. D., Jackson, J. B., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci120216 · Cited by 125 · see citing works
Sridharan, D. M., Asaithamby, A., Bailey, S. M., Costes, S. V., Doetsch, P. W., Dynan, W. S., Kronenberg, A., Rithidech, K. N., Saha, J., Snijders, A. M., et al. (2015) · Radiation Research · doi:10.1667/rr13804.1 · Cited by 124 · see citing works
Genetic and epigenetic modulation of telomerase activity in development and disease
Liu, L., Lai, S. R., Andrews, L. G., & Tollefsbol, T. O. (2004) · Gene · doi:10.1016/j.gene.2004.06.011 · Cited by 121 · see citing works
On the capturing of low-energy electrons by DNA
Ray, S. G., Daube, S. S., & Naaman, R. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407020102 · Cited by 118 · see citing works
Calado, R. T., Cooper, J. N., Padilla‐Nash, H. M., Sloand, E. M., Wu, C. O., Scheinberg, P., Ried, T., & Young, N. S. (2011) · Leukemia · doi:10.1038/leu.2011.272 · Cited by 113 · see citing works
Imetelstat (GRN163L) - Telomerase-Based Cancer Therapy
Röth, A., Harley, C. B., & Baerlocher, G. M. (2009) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-642-01222-8_16 · Cited by 108 · see citing works
Erdmann, N., Liu, Y., & Harrington, L. A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401580101 · Cited by 107 · see citing works
Telomere length mediates the effects of telomerase on the cellular response to genotoxic stress
Rubio, M. Á., Davalos, A. R., & Campisi, J. (2004) · Experimental Cell Research · doi:10.1016/j.yexcr.2004.04.004 · Cited by 105 · see citing works
Mammalian telomeres and telomerase: why they matter for cancer and aging
Blasco, M. A. (2003) · European Journal of Cell Biology · doi:10.1078/0171-9335-00335 · Cited by 104 · see citing works
Ulaner, G. A., Hoffman, A. R., Otero, J. E., Huang, H., Zhao, Z., Mazumdar, M., Gorlick, R. G., Meyers, P. A., Healey, J. H., & Ladanyi, M. (2004) · Genes Chromosomes and Cancer · doi:10.1002/gcc.20074 · Cited by 99 · see citing works
Ward, R. J., & Autexier, C. (2005) · Molecular Pharmacology · doi:10.1124/mol.105.011494 · Cited by 99 · see citing works
Many ways to telomere dysfunction: in vivo studies using mouse models
Goytisolo, F. A., & Blasco, M. A. (2002) · Oncogene · doi:10.1038/sj.onc.1205085 · Cited by 94 · see citing works
Massive Telomere Loss Is an Early Event of DNA Damage-induced Apoptosis
Ramı́rez, R., Carracedo, J., Jiménez, R., Canela, A., Herrera, E., Aljama, P., & Blasco, M. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m206818200 · Cited by 94 · see citing works
Telomerase: regulation, function and transformation
Dong, C. K., Masutomi, K., & Hahn, W. C. (2005) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2004.12.005 · Cited by 94 · see citing works
Jakob, S., Schröeder, P., Lukosz, M., Büchner, N., Spyridopoulos, I., Altschmied, J., & Haendeler, J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805138200 · Cited by 92 · see citing works
Cheng, H., Fan, X., Lawson, W. E., Paueksakon, P., & Harris, R. C. (2015) · Kidney International · doi:10.1038/ki.2015.69 · Cited by 89 · see citing works
Canela, A., Martín-Caballero, J., Flores, J. M., & Blasco, M. A. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.10.4275-4293.2004 · Cited by 90 · see citing works
Telomere dysfunction in aging and cancer
Gilley, D. P., Tanaka, H., & Herbert, B. (2004) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2004.09.003 · Cited by 89 · see citing works
Aging and radiation: bad companions
Hernández, L., Terradas, M., Camps, J., Martı́n, M., Tusell, L., & Genescà, A. (2015) · Aging Cell · doi:10.1111/acel.12306 · Cited by 89 · see citing works
Sharma, G. G., Hwang, K.-K., PANDITA, R. K., Gupta, A. K. D., Dhar, S., Parenteau, J., Agarwal, M., Worman, H. J., Wellinger, R. J., & Pandita, T. K. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.22.8363-8376.2003 · Cited by 89 · see citing works
Samper, E., Goytisolo, F. A., Murcia, J. M., González‐Suárez, E., Cigudosa, J. C., de MURCIA, G., & Blasco, M. A. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.200103049 · Cited by 86 · see citing works
Nakamura, M., Masutomi, K., Kyo, S., Hashimoto, M., Maida, Y., Kanaya, T., Tanaka, M., Hahn, W. C., & Inoue, M. (2005) · Human Gene Therapy · doi:10.1089/hum.2005.16.859 · Cited by 85 · see citing works
Telomeres: Hallmarks of radiosensitivity
Ayouaz, A., Raynaud, C. M., Heride, C., Revaud, D., & Sabatier, L. (2007) · Biochimie · doi:10.1016/j.biochi.2007.09.011 · Cited by 84 · see citing works
Reversible Manipulation of Telomerase Expression and Telomere Length
Rubio, M. Á., Kim, S., & Campisi, J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203747200 · Cited by 82 · see citing works
The Hallmarks of Cancer and the Radiation Oncologist: Updating the 5Rs of Radiobiology
Good, J., & Harrington, K. J. (2013) · Clinical Oncology · doi:10.1016/j.clon.2013.06.009 · Cited by 83 · see citing works
Ding, X., Cheng, J., Pang, Q., Wei, X., Zhang, X., Wang, P., Yuan, Z., & Qian, D. (2019) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2019.08.009 · Cited by 83 · 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
Self-citationA role for Brca1 in chromosome end maintenance
McPherson, J. P., Hande, M. P., Poonepalli, A., Lemmers, B., Matysiak‐Zablocki, E., Migon, E., Shehabeldin, A., Porras, A., Karásková, J., Vukovic, B., et al. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl002 · Cited by 77 · see citing works
Akiyama, M., Yamada, O., Kanda, N., Akita, S., Kawano, T., Ohno, T., Mizoguchi, H., Eto, Y., Anderson, K. C., & Yamada, H. (2002) · Cancer Letters · doi:10.1016/s0304-3835(01)00838-2 · Cited by 74 · see citing works
Bejarano, L., Schuhmacher, A. J., Méndez, M., Megı́as, D., Blanco‐Aparicio, C., Martı́nez, S., Pastor, J., Squatrito, M., & Blasco, M. A. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.10.006 · Cited by 76 · see citing works
Low-Energy Electron Transmission through Thin-Film Molecular and Biomolecular Solids
Naaman, R., & Sanche, L. (2007) · Chemical Reviews · doi:10.1021/cr040200j · Cited by 75 · see citing works
The role of DNA damage response proteins at telomeres—an “integrative” model
Slijepčević, P. (2006) · DNA repair · doi:10.1016/j.dnarep.2006.05.038 · Cited by 73 · see citing works
Shortened telomeres join to DNA breaks interfering with their correct repair
Latre, L. (2003) · Experimental Cell Research · doi:10.1016/s0014-4827(03)00134-4 · Cited by 72 · see citing works
M’kacher, R., Griscelli, A. B., Girinsky, T., Koscielny, S., Delhommeau, F., Dossou, J., Violot, D., Leclercq, É., Courtier, M. H., Béron‐Gaillard, N., et al. (2007) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2007.01.050 · Cited by 72 · see citing works
Attardi, L. D. (2004) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2004.04.019 · Cited by 73 · see citing works
Paek, A. L., Kaochar, S., Jones, H., Elezaby, A., Shanks, L., & Weinert, T. A. (2009) · Genes & Development · doi:10.1101/gad.1862709 · Cited by 72 · see citing works
Phosphorylation of H2AX at Short Telomeres in T Cells and Fibroblasts
Hao, L.-Y., Strong, M. A., & Greider, C. W. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403924200 · Cited by 71 · see citing works
Telomere-driven genomic instability in cancer cells
Desmaze, C., Soria, J., Freulet-Marrière, M.-A., Mathieu, N., & Sabatier, L. (2003) · Cancer Letters · doi:10.1016/s0304-3835(02)00704-8 · Cited by 71 · see citing works
Gómez‐Millán, J., Goldblatt, E. M., Gryaznov, S. M., Mendonca, M. S., & Herbert, B. (2006) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2006.09.038 · Cited by 72 · see citing works
Targeting telomerase for its advent in cancer therapeutics
Bajaj, S., Kumar, M. S., Peters, G. J., & Mayur, Y. (2020) · Medicinal Research Reviews · doi:10.1002/med.21674 · Cited by 71 · see citing works
Shin, K.-H., Kang, M., Dicterow, E., Kameta, A., Baluda, M. A., & Park, N. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-0669-3 · Cited by 69 · see citing works
Telomere restoration and extension of proliferative lifespan in dyskeratosis congenita fibroblasts
Westin, E. R., Chavez, E. A., Lee, K. M., Gourronc, F. A., Riley, S., Lansdorp, P. M., Goldman, F. D., & Klingelhutz, A. J. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00288.x · Cited by 67 · see citing works
Qi, L., Strong, M. A., Karim, B. O., Armanios, M. Y., Huso, D. L., & Greider, C. W. (2003) · PubMed · Cited by 68 · see citing works
Ionizing radiation and heart risks
Bhattacharya, S., & Asaithamby, A. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2016.01.045 · Cited by 67 · see citing works
Control of Cellular Aging, Tissue Function, and Cancer by p53 Downstream of TelomeresPreprint
Roake, C. M., & Artandi, S. E. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026088 · Cited by 67 · see citing works
Self-citationKesäniemi, J., Lavrinienko, A., Tukalenko, E., Boratyński, Z., Kivisaari, K., Mappes, T., Milinevsky, G. P., Møller, A. P., Mousseau, T. A., & Watts, P. C. (2019) · Scientific Reports · doi:10.1038/s41598-018-37164-8 · Cited by 63 · see citing works
Sishc, B. J., Nelson, C. B., McKenna, M. J., Battaglia, C. L. R., Herndon, A. K., Idate, R., Liber, H. L., & Bailey, S. M. (2015) · Frontiers in Oncology · doi:10.3389/fonc.2015.00257 · Cited by 62 · see citing works
Berardinelli, F., Coluzzi, E., Sgura, A., & Antoccia, A. (2017) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2017.02.004 · Cited by 61 · see citing works
Accelerated Telomere Shortening and Telomere Abnormalities in Radiosensitive Cell Lines
Cabuy, E., Newton, C., Joksiċ, G., Woodbine, L. J., Koller, B. H., Jeggo, P. A., & Slijepčević, P. (2005) · Radiation Research · doi:10.1667/rr3376 · Cited by 62 · see citing works
Telomere dysfunction and genome instability
Frías-López, C. (2012) · Frontiers in bioscience · doi:10.2741/4044 · Cited by 62 · see citing works
- Authors
- Wong, K.-K., Chang, S., Weiler, S. R., Ganesan, S., Chaudhuri, J., Zhu, C., Artandi, S. E., Rudolph, K. L., Gottlieb, G. J., Chin, L., Alt, F. W., & DePinho, R. A.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Quest Diagnostics (United States) (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- DePinho, Ronald A.
- ORCID
- Venue
- Nature Genetics
- Published
- 2000-09
- Volume
- 26
- Issue
- 1
- Pages
- 85-88
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1538980175
- Cited by
- 309
- References
- 30
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 6 · 2022: 3 · 2021: 5 · 2020: 8 · 2019: 14 · 2018: 7 · 2017: 7 · 2016: 9 · 2015: 19 · 2014: 9 · 2013: 13 · 2012: 12
- FWCI
- 12.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hd028317-05, 5r01hd034880-04, 5k08ar002104-04)
- National Institute on Aging (K08AG001019)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (K08AR02104-01)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD34880, R01 HD28317)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- telomere dysfunction, telomerase, radiosensitivity, DNA repair, non-homologous end joining, chromosomal instability, chromosomal abnormalities, apoptosis, clonogenic survival, thymocytes, mouse embryonic fibroblasts
- MeSH terms
- Animals, Cell Nucleus, Cell Survival, Chromosome Aberrations, Chromosomes, DNA Repair, Dose-Response Relationship, Radiation, Fibroblasts, Genotype, Kinetics, Mice, Transgenic, Models, Genetic, Radiation Tolerance, Radiation, Ionizing, Thymus Gland, Time Factors, Telomere, Apoptosis, In Situ Nick-End Labeling, Mice, DNA Fragmentation
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