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Telomere Length Dynamics and Chromosomal Instability in Cells Derived from Telomerase Null Mice
Open accessAbstract
To study the effect of continued telomere shortening on chromosome stability, we have analyzed the telomere length of two individual chromosomes (chromosomes 2 and 11) in fibroblasts derived from wild-type mice and from mice lacking the mouse telomerase RNA (mTER) gene using quantitative fluorescence in situ hybridization. Telomere length at both chromosomes decreased with increasing generations of mTER−/− mice. At the 6th mouse generation, this telomere shortening resulted in significantly shorter chromosome 2 telomeres than the average telomere length of all chromosomes. Interestingly, the most frequent fusions found in mTER−/− cells were homologous fusions involving chromosome 2. Immortal cultures derived from the primary mTER−/− cells showed a dramatic accumulation of fusions and translocations, revealing that continued growth in the absence of telomerase is a potent inducer of chromosomal instability. Chromosomes 2 and 11 were frequently involved in these abnormalities suggesting that, in the absence of telomerase, chromosomal instability is determined in part by chromosome-specific telomere length. At various points during the growth of the immortal mTER−/− cells, telomere length was stabilized in a chromosome-specific man-ner. This telomere-maintenance in the absence of telomerase could provide the basis for the ability of mTER−/− cells to grow indefinitely and form tumors.
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“In the G5-G6 TERCÀ/À tissues, there was clear cytogenetic evidence of progressive telomere erosion including 'signal-free' ends, chromosomal end-to-end fusions and anaphase bridging at mitosis (60)(61)(62).”
From Telomeres and telomerase in cancer (2010) · cites this paper as [61]
In the citing paper
“G5-G6 TERC mice became infertile, showed high rates of apoptosis in testis and germ cell depletion, exhibited impaired bone marrow function and diminished proliferation of lymphocytes (61).”
From Telomeres and telomerase in cancer (2010) · cites this paper as [61]
In the citing paper
“Indeed, continued breeding of first generation (G1) TERCÀ/À mice to yield successive generations of TERCÀ/À mice resulted in progressive loss of telomere reserves and ultimately provoked severe degeneration of highly proliferative tissues.”
From Telomeres and telomerase in cancer (2010) · cites this paper as [61]
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Citations
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 · cited 1×
“Indeed, telomere shortening to a critical length has been proposed to limit the life span of somatic cells in humans (Harley et al., 1990; Counter et al., 1992).”
BackgroundExtension 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 · cited 2×
“It has been recently shown that the introduction of the telomerase catalytic subunit in primary human cells is sufficient to restore enzymatic activity, to elongate and maintain telomeres, and, in some cell types, to sustain immortal growth ( Bodnar et al., 1998; Wang et al., 1998; Kiyono et al., 1998).”
Structure and function of telomeres
Blackburn, E. H. (1991) · Nature · doi:10.1038/350569a0 · Cited by 3,596
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 · cited 1×
“In such cells the enzyme telomerase seems to be the main mechanism for the maintenance of telomere length (Greider and Blackburn, 1985; Morin, 1989; Yu et al., 1990; Singer and Gottschling, 1994; McEachern and Blackburn, 1996; Nakamura et al., 1997).”
BackgroundA survey of telomerase activity in human cancer
Shay, J. W., & Bacchetti, S. (1997) · European Journal of Cancer · doi:10.1016/s0959-8049(97)00062-2 · Cited by 2,794 · cited 1×
“These mechanisms, which can be either telomerase dependent (reviewed in Shay and Bacchetti, 1997 ) or independent (this paper and Bryan et al., 1995, 1997), can prevent telomeres from further shortening, allowing the immortal growth of cells that have critically short telomeres and a high degree of genetic instability.”
BackgroundTodaro, G. J., & Green, H. (1963) · The Journal of Cell Biology · doi:10.1083/jcb.17.2.299 · Cited by 2,747 · cited 1×
“col (Todaro and Green, 1963) in dishes of 10 cm diam, seeding 10 6 cells ev-”
Telomerase Catalytic Subunit Homologs from Fission Yeast and Human
Nakamura, T. M., Morin, G. B., Chapman, K. B., Weinrich, S. L., Andrews, W. H., Lingner, J., Harley, C. B., & Cech, T. R. (1997) · Science · doi:10.1126/science.277.5328.955 · Cited by 2,256
The RNA Component of Human Telomerase
Feng, J., Funk, W. D., Wang, S.-S., Weinrich, S. L., Avilion, A. A., Chiu, C.-P., Adams, R. R., Chang, E., Allsopp, R. C., Yu, J., et al. (1995) · Science · doi:10.1126/science.7544491 · Cited by 2,227 · cited 2×
“, 1998), an RNA molecule that contains the template for the synthesis of telomeric repeats (Greider and Blackburn, 1989; Singer and Gottschling, 1994; Blasco et al., 1995; Feng et al., 1995; McEachern and Blackburn, 1995), and other associated proteins (Collins et al.”
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 · cited 15×
“The details are explained elsewhere (Blasco et al., 1997).”
InfluentialSelf-citationCounter, C. M., Avilion, A. A., LeFeuvre, C. E., Stewart, N. G., Greider, C. W., Harley, C. B., & Bacchetti, S. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05245.x · Cited by 2,096 · cited 1×
“Indeed, telomere shortening to a critical length has been proposed to limit the life span of somatic cells in humans (Harley et al., 1990; Counter et al., 1992).”
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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
“Here we find that ditions (Hande et al., 1999). the ability of the mTR2/2 mice to respond to various physiological stresses is compromised and declines Progressive Increase in the Rate of Spontaneous with increasing age of the mouse.”
BackgroundSelf-citationHemann, M. T., Strong, M. A., Hao, L.-Y., & Greider, C. W. (2001) · Cell · doi:10.1016/s0092-8674(01)00504-9 · Cited by 1,219
“) mTRϪ/Ϫ mice (Table 1) (Blasco et al., 1997; Hemann et al., 2001b; Lee et al., 1998).”
Aubert, G., & Lansdorp, P. M. (2008) · Physiological Reviews · doi:10.1152/physrev.00026.2007 · Cited by 1,188
“The technique is well established to study telomere biology in many settings (8, 81).”
BackgroundMethodSelf-citationOxygen sensitivity severely limits the replicative lifespan of murine fibroblasts
Parrinello, S., Samper, E., Krtolica, A., Goldstein, J., Melov, S., & Campisi, J. (2003) · Nature Cell Biology · doi:10.1038/ncb1024 · Cited by 1,116
“In addition, our finding that mTR −/− MEFs do not senesce in 3% oxygen, in contrast to telomerase-negative human cells, is most probably caused by the ability of mouse chromosomes to stabilize telomeres in the absence of telomerase until alternative telomere maintenance pathways are induce”
BackgroundSelf-citationInhibition of telomerase limits the growth of human cancer cells
Hahn, W. C., Stewart, S. A., Brooks, M. W., York, S. G., Eaton, E. N., Kurachi, A. L., Beijersbergen, R. L., Knoll, J. H. M., Meyerson, M. M., & Weinberg, R. A. (1999) · Nature Medicine · doi:10.1038/13495 · Cited by 1,038
Telomeres and telomerase in cancer
Artandi, S. E., & DePinho, R. A. (2010) · Carcinogenesis · doi:10.1093/carcin/bgp268 · Cited by 823
Senescence and aging: the critical roles of p53
Rufini, A., Tucci, P., Celardo, I., & Melino, G. (2013) · Oncogene · doi:10.1038/onc.2012.640 · Cited by 798
Linking functional decline of telomeres, mitochondria and stem cells during ageing
Sahin, E., & DePinho, R. A. (2010) · Nature · doi:10.1038/nature08982 · Cited by 759
“The severity of these degenerative phenotypes parallels the degree of telomere dysfunction in successive Terc −/− generations, as measured by the number of chromosomal fusions and anaphase bridges and, in a more recent study, the number of DNA damage foci at telomere”
Telomere length, stem cells and aging
Blasco, M. A. (2007) · Nature Chemical Biology · doi:10.1038/nchembio.2007.38 · Cited by 747
“ALT mechanisms are also activated in Terc -deficient mice in cultured mouse embryonic fibroblasts and embryonic stem cell”
BackgroundSelf-citationThe epigenetic regulation of mammalian telomeres
Blasco, M. A. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2047 · Cited by 600
“In mammals, the telomerase-deficient mouse model has been instrumental in demonstrating telomere maintenance in the absence of telomerase, in both cultured mouse embryonic fibroblasts (MEFs”
BackgroundSelf-citationAlternative lengthening of telomeres in mammalian cells
Henson, J. D., Neumann, A. A., Yeager, T. R., & Reddel, R. R. (2002) · Oncogene · doi:10.1038/sj.onc.1205058 · Cited by 684
“To date, clear evidence for ALT activity has only been found in abnormal situations, including human tumors, immortalized human cell lines (Table 1), and in telomerase-null mouse cell lines (Bryan et al., 1995, 1997a; Hande et al., 1999; Niida et al., 2000).”
BackgroundAnti-proliferative activity of silver nanoparticles
Asharani, P. V., Hande, M. P., & Valiyaveettil, S. (2009) · BMC Cell Biology · doi:10.1186/1471-2121-10-65 · Cited by 663
“FISH was performed on metaphase spreads using telomere and centromere specific peptide nucleic acid (PNA) probes (Applied Biosystems) labelled with Cy-3 and FITC respectively as explained earlier [38,39].”
MethodSelf-citationTelomerase in the human organism
Collins, K., & Mitchell, J. R. (2002) · Oncogene · doi:10.1038/sj.onc.1205083 · Cited by 616
“The murine ALT lines that arise readily in the absence of telomerase maintain atypically short rather than long telomeres (Hande et al., 1999), suggesting some species-speci®city in ALT pathway requirements.”
BackgroundGarcía‐Cao, M., O’Sullivan, R. J., Peters, A. H. F. M., Jenuwein, T., & Blasco, M. A. (2003) · Nature Genetics · doi:10.1038/ng1278 · Cited by 557
Self-citationDisease states associated with telomerase deficiency appear earlier in mice with short telomeres
Herrera, E., Samper, E., Martín‐Caballero, J., Flores, J. M., Lee, H., & Blasco, M. A. (1999) · The EMBO Journal · doi:10.1093/emboj/18.11.2950 · Cited by 471
“Disease states associated with telomerase deficiency appear earlier in mice with short telomeres”
BackgroundResultInfluentialSelf-citationPutting the stress on senescence
Serrano, M., & Blasco, M. A. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00278-7 · Cited by 413
Self-citationTelomere lengthening early in development
Liu, L., Bailey, S. M., Okuka, M., Muñoz, P., Li, C., Zhou, L., Wu, C., Czerwiec, E., Sandler, L., Seyfang, A., et al. (2007) · Nature Cell Biology · doi:10.1038/ncb1664 · Cited by 405
“Mammalian telomeres consist of repetitive G-rich sequences and associated proteins, which cap the ends of linear chromosomes and maintain chromosomal stabilit”
BackgroundSelf-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
T cells and aging january 2002 update
Pawelec, G. (2002) · Frontiers in bioscience · doi:10.2741/a831 · Cited by 372
CAJAL BODIES: A Long History of Discovery
Cioce, M., & Lamond, A. I. (2005) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.20.010403.103738 · Cited by 372
“This contributes to genomic instability (Hande et al. 1999).”
Telomere length regulates the epigenetic status of mammalian telomeres and subtelomeres
Benetti, R., García‐Cao, M., & Blasco, M. A. (2007) · Nature Genetics · doi:10.1038/ng1952 · Cited by 375
“These findings agree with previous reports showing activation of ALT pathways in late-generation Terc −/− cell”
ResultSelf-citationChromosomal instability in ulcerative colitis is related to telomere shortening
O'Sullivan, J. N., Bronner, M. P., Brentnall, T. A., Finley, J. C., Shen, W.-T., Emerson, S., Emond, M. J., Gollahon, K. A., Moskovitz, A. H., Crispin, D. A., et al. (2002) · Nature Genetics · doi:10.1038/ng989 · Cited by 346
“, resulting in cycles of chromatin bridge breakage and fusio”
BackgroundAubert, 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
“The technique is well established to study telomere biology in many settings [52, 53] and may be a good choice for measuring telomere length in rare cells [54]; the main characteristics of the assay are summarized in Table 1.”
MethodMathon, N. F., & Lloyd, A. C. (2001) · Nature reviews. Cancer · doi:10.1038/35106045 · Cited by 313
“A likely explanation for this anomalous finding is that shortened telomeres have a dual effect: they initiate checkpoint signals that provoke a cell-cycle arrest or trigger apoptosis, but they can also cause chromosomal instabilit”
BackgroundResolution of anaphase bridges in cancer cells
Hoffelder, D. R., Luo, L., Burke, N., Watkins, S. C., Gollin, S. M., & Saunders, W. S. (2004) · Chromosoma · doi:10.1007/s00412-004-0284-6 · Cited by 277
“In addition to DNA breaks, anaphase bridges can be caused by abnormal shortening of the telomeres (de Lange 2002; Hande et al. 1999) or by persistent chromatid cohesion (Coelho et al.”
BackgroundAccumulation 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
Self-citationSamper, E., Flores, J. M., & Blasco, M. A. (2001) · The EMBO Reports · doi:10.1093/embo-reports/kve174 · Cited by 263
“Chromosome 2 was chosen for the study because, in the mouse, this chromosome has shorter telomeres than average (Hande et al., 1999).”
MethodSelf-citationConstitutional short telomeres are strong genetic susceptibility markers for bladder cancer
Broberg, K., Björk, J., Paulsson, K., Höglund, M., & Albin, M. (2005) · Carcinogenesis · doi:10.1093/carcin/bgi063 · Cited by 255
ATM, a central controller of cellular responses to DNA damage
Khanna, K. K., Lavin, M. F., Jackson, S. P., & Mulhern, T. D. (2001) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400874 · Cited by 260
“Indeed, impairment of telomere function through telomere attrition or loss of telomere binding proteins leads to the triggering of DNA damage responses and to telomeres engaging in inappropritate recombination events with one another and with other loci.(183,184) In mammals, telomeres are covered by binding proteins (…”
BackgroundCoexistence of Alternative Lengthening of Telomeres and Telomerase in hTERT-Transfected GM847 Cells
Perrem, K., Colgin, L. M., Neumann, A. A., Yeager, T. R., & Reddel, R. R. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.12.3862-3875.2001 · Cited by 247
“Telomeres are specialized structures consisting, in human cells, of TTAGGG repeat sequences (4, 33) which, together with specific binding proteins (5), form caps at the ends of chromosomes that are essential for chromosome stability (11, 17).”
BackgroundFang, B., Zborowski, M., & Moore, L. R. (1999) · Cytometry · doi:10.1002/(sici)1097-0320(19990801)36:4 · Cited by 33
Self-citationMitochondrial dysfunction leads to telomere attrition and genomic instability
Liu, L., Trimarchi, J. R., Smith, P. J. S., & Keefe, D. L. (2002) · Aging Cell · doi:10.1046/j.1474-9728.2002.00004.x · Cited by 237
Telomere length in leukocyte subpopulations of patients with aplastic anemia
Brümmendorf, T. H., Maciejewski, J. P., Mak, J., Young, N. S., & Lansdorp, P. M. (2001) · Blood · doi:10.1182/blood.v97.4.895 · Cited by 233
Self-citationSuram, A., Kaplunov, J., Patel, P. L., Ruan, H., Cerutti, A., Boccardi, V., Fumagalli, M., Di Micco, R., Mirani, N., Gurung, R. L., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.132 · Cited by 227
“Telomeres were detected with a Cy3-conjugated Telomere PNA probe (Cy3-OO-(CCCTAA)3; Panagene, Korea) by FISH as described in Hande et al (1999), with the only modification of a DNA denaturation step in 0.5M NaOH 1M NaCl for 8min.”
Self-citationLiving with Genome Instability: Plant Responses to Telomere Dysfunction
Říha, K., McKnight, T. D., Griffing, L. R., & Shippen, D. E. (2001) · Science · doi:10.1126/science.1057110 · Cited by 226
Mammalian telomeres and telomerase
Collins, K. (2000) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00103-4 · Cited by 226
Telomere Length Assessment in Human Archival Tissues
Meeker, A. K., Gage, W. R., Hicks, J. L., Simon, I., Coffman, J. R., Platz, E. A., March, G. E., & De Marzo, A. M. (2002) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)62553-9 · Cited by 209
A ‘higher order’ of telomere regulation: telomere heterochromatin and telomeric RNAs
Schoeftner, S., & Blasco, M. A. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.197 · Cited by 232
“In this regard, recombination-based ALT pathways are activated in telomerase-deficient mice (Blasco et al, 1997; Hande et al, 1999; Rudolph et al, 1999; Herrera et al, 2000; Niida et al, 2000; Chang et al, 2003).”
BackgroundSelf-citationTelomere 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
“A cardinal indicator of telomere dysfunction is endto-end chromosomal fusion, which becomes more frequent in later-generation Terc / mice (15).”
BackgroundFitzgerald, M. S., Říha, K., Gao, F., Ren, S., McKnight, T. D., & Shippen, D. E. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.26.14813 · Cited by 210
Brümmendorf, T. H., Holyoake, T. L., Rufer, N., Barnett, M. J., Schulzer, M., Eaves, C. J., Eaves, A. C., & Lansdorp, P. M. (2000) · Blood · doi:10.1182/blood.v95.6.1883 · Cited by 198
Self-citationPathways 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 194
Chang, S., Khoo, C. M., Naylor, M. L., Maser, R. S., & DePinho, R. A. (2003) · Genes & Development · doi:10.1101/gad.1029903 · Cited by 183
“1B; Blasco et al. 1997; Hande et al. 1999; Hemann et al. 2001).”
BackgroundInfluentialDNA-PKcs is critical for telomere capping
Gilley, D. P., Tanaka, H., Hande, M. P., Kurimasa, A., Li, G. C., Oshimura, M., & Chen, D. J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.261574698 · Cited by 177
Self-citationThymoquinone Induces Telomere Shortening, DNA Damage and Apoptosis in Human Glioblastoma Cells
Gurung, R. L., Lim, S. N., Khaw, A. K., Soon, J. F. F., Shenoy, K., Ali, S. M., Jayapal, M., Sethu, S., Baskar, R., & Hande, M. P. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012124 · Cited by 172
“Quantitative fluorescence in situ hybridisation (qFISH) was performed using telomere sequence-specific peptide nucleic acid (PNA) probe labelled with Cy3 as described [17,18].”
MethodSelf-citationPancolonic chromosomal instability precedes dysplasia and cancer in ulcerative colitis.
Rabinovitch, P. S., Dziadon, S. M., Brentnall, T. A., Emond, M. J., Crispin, D. A., Haggitt, R. C., & Bronner, M. P. (1999) · PubMed · Cited by 174
Neural stem cells and regulation of cell number
Sommer, L., & Rao, M. S. (2002) · Progress in Neurobiology · doi:10.1016/s0301-0082(01)00022-3 · Cited by 175
“Indeed, oncogenic transformation is increased manifold in telomerase knockout mice (Blasco et al., 1997; Hande et al., 1999).”
BackgroundIrregular telomeres impair meiotic synapsis and recombination in mice
Liu, L., Franco, S., Spyropoulos, B., Møens, P. B., Blasco, M. A., & Keefe, D. L. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400755101 · Cited by 173
Self-citationTelomere maintenance by telomerase and by recombination can coexist in human cells
Cerone, M. A. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.18.1945 · Cited by 173
“Activation of ALT in tumor cells is a much rarer event than activation of telomerase (20), and may normally occur under selective pressure when expression of the enzyme is prevented (38,39).”
BackgroundCardiac ageing: extrinsic and intrinsic factors in cellular renewal and senescence
Gude, N. A., Broughton, K. M., Firouzi, F., & Sussman, M. A. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0061-5 · Cited by 172
Telomeres, telomerase and cancer: an up-date
Dhaene, K., Marck, E. V., & Parwaresch, R. M. (2000) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s004280000189 · Cited by 166
“They exhibited defective spermatogenesis and haematopoiesis, coupled with telomere-length reductions and abnormal cytogenetic profiles, indicating an essential role for telomerase and telomeres in the maintenance of genomic integrity and in the long-term viability of high-renewal tissues [29, 64].”
Telomere Dysfunction Triggers Developmentally Regulated Germ Cell Apoptosis
Hemann, M. T., Rudolph, K. L., Strong, M. A., DePinho, R. A., Chin, L., & Greider, C. W. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.7.2023 · Cited by 162
Louis, S. F., Vermolen, B. J., Garini, Y., Young, I. T., Guffei, A., Lichtensztejn, Z., Kuttler, F., Chuang, T., Moshir, S., Mougey, V., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407512102 · Cited by 159
Ferrón, S., Mira, H., Franco, S., Cano-Jaimez, M., Bellmunt, E., Ramírez, C., Fariñas, I., & Blasco, M. A. (2004) · Development · doi:10.1242/dev.01215 · Cited by 152
“Fluorescence beads (Molecular Probes, Eugene, OR, USA) were used as quantification standards, as described previously (Hande et al., 1999).”
MethodSelf-citationTelomerase and human tumorigenesis
Stewart, S. A., & Weinberg, R. A. (2000) · Seminars in Cancer Biology · doi:10.1006/scbi.2000.0339 · Cited by 152
Telomeres, interstitial telomeric repeat sequences, and chromosomal aberrations
Bolzán, A. D., & de Bianchi, M. S. A. (2006) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2005.12.003 · Cited by 151
Telomere maintenance and cancer ? look, no telomerase
Neumann, A. A., & Reddel, R. R. (2002) · Nature reviews. Cancer · doi:10.1038/nrc929 · Cited by 159
“cgi?l=21748"> Terc , are also able to undergo immortalizatio”
BackgroundThe telomere theory of reproductive senescence in women
Keefe, D. L., Marquard, K. L., & Liu, L. (2006) · Current Opinion in Obstetrics & Gynecology · doi:10.1097/01.gco.0000193019.05686.49 · Cited by 146
Telomeres and Telomerase in Aging, Regeneration and Cancer
Djojosubroto, M. W., Choi, Y. S., Lee, H., & Rudolph, K. L. (2003) · Molecules and Cells · doi:10.1016/s1016-8478(23)13723-x · Cited by 146
Impaired germinal center reaction in mice with short telomeres
Herrera, E., Martínez‐A, C., & Blasco, M. A. (2000) · The EMBO Journal · doi:10.1093/emboj/19.3.472 · Cited by 144
“The existence of telomere-rescue mechanisms in late generation mTR–/– mice is supported by previous reports showing that late generation mTR–/– cells in culture can maintain telomeres without telomerase (Hande et al., 1999).”
BackgroundResultInfluentialSelf-citationTelomere shortening in mTR−/− embryos is associated with failure to close the neural tube
Herrera, E., Samper, E., & Blasco, M. A. (1999) · The EMBO Journal · doi:10.1093/emboj/18.5.1172 · Cited by 147
“However, telomeres shorten progressively and this shortening is accompanied by an increase in chromosomal abnormalities (Blasco et al., 1997; Hande et al., 1999b).”
BackgroundSelf-citationFerreira, M. G., Miller, K. M., & Cooper, J. P. (2004) · Molecular Cell · doi:10.1016/s1097-2765(03)00531-8 · Cited by 142
Long-term repopulating ability of telomerase-deficient murine hematopoietic stem cells
Samper, E., Fernández, P., Eguı́a, R., Martı́n-Rivera, L., Bernad, A., Blasco, M. A., & Aracil, M. (2002) · Blood · doi:10.1182/blood.v99.8.2767 · Cited by 140
Self-citationAlternative lengthening of telomeres in normal mammalian somatic cells
Neumann, A. A., Watson, C. M., Noble, J. R., Pickett, H. A., Tam, P. P. L., & Reddel, R. R. (2013) · Genes & Development · doi:10.1101/gad.205062.112 · Cited by 137
Niida, H., Shinkai, Y., Hande, M. P., Matsumoto, T., Takehara, S., Tachibana, M., Oshimura, M., Lansdorp, P. M., & Furuichi, Y. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.4115-4127.2000 · Cited by 138
“Metaphase spreads at selected PDL from wild-type (WT) and mTER ES cells were hybridized as described earlier (17, 18).”
BackgroundMethodInfluentialSelf-citationIntratumor genetic heterogeneity in advanced human colorectal adenocarcinoma
Baisse, B., Bouzourène, H., Saraga, E. P., Bosman, F. T., & Benhattar, J. (2001) · International Journal of Cancer · doi:10.1002/ijc.1343 · Cited by 135
Clues to catastrophic telomere loss in mammals from yeast telomere rapid deletion
Lustig, A. J. (2003) · Nature Reviews Genetics · doi:10.1038/nrg1207 · Cited by 138
“This result contrasts with what is seen in wild-type strains and with the slower 2–7-kb loss of sequences per generation that is seen in the murine telomerase RNA-knockout strain”
ResultNasir, L., Devlin, P., McKevitt, T. P., Rutteman, G. R., & Argyle, D. J. (2001) · Neoplasia · doi:10.1038/sj.neo.7900173 · Cited by 136
Telomere biology in mammalian germ cells and during development
Bekaert, S., Derradji, H., & Baatout, S. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.06.023 · Cited by 131
“This was due mainly to the absence of telomerase activity and was associated with an increase in aneuploidy and end-to-end chromosomal fusions (Blasco et al., 1997; Hande et al., 1999).”
BackgroundFunctional interaction between DNA‐PKcs and telomerase in telomere length maintenance
Espejel, S., Franco, S., Sgura, A., Gae, D., Bailey, S. M., Taccioli, G. E., & Blasco, M. A. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf593 · Cited by 130
Self-citationLoss of DNA Polymerase ζ Causes Chromosomal Instability in Mammalian Cells
Wittschieben, J. P., Reshmi, S. C., Gollin, S. M., & Wood, R. D. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2982 · Cited by 131
“In contrast, chromosomes from telomerase null cells with shortened telomeres form increased numbers of p-p arm fusions (58).”
BackgroundTelomere Length in Peripheral Leukocyte DNA and Gastric Cancer Risk
Hou, L., Savage, S. A., Blaser, M. J., Perez-Perez, G., Hoxha, M., Dioni, L., Pegoraro, V., Dong, L. M., Zatoński, W. A., Lissowska, J., et al. (2009) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-09-0347 · Cited by 124
“Telomeraseknockout mouse models, in which animals possess critically short telomeres, exhibit increased cancer rates (9-11).”
BackgroundExtra-chromosomal telomeric DNA in cells from Atm-/- mice and patients with ataxia-telangiectasia
Hande, M. P. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.5.519 · Cited by 125
“2) suggested less telomere shortening relative to Atm+/+ cells than observed at chromosome ends by Q-FISH (Fig.”
BackgroundMethodInfluentialSelf-citationA role for the Rb family of proteins in controlling telomere length
García-Cao, M., Gonzalo, S., Dean, D., & Blasco, M. A. (2002) · Nature Genetics · doi:10.1038/ng1011 · Cited by 120
Self-citationLong noncoding RNAs in aging and age-related diseases
Kour, S., & Rath, P. C. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.12.001 · Cited by 123
Öztürk, S., Sözen, B., & Demir, N. (2013) · Molecular Human Reproduction · doi:10.1093/molehr/gat055 · Cited by 114
“Most of these unfavorable effects presumably resulted from the fusion of the chromosomes, various translocations and loss of certain chromosomal sites due to progressive loss of the telomeric DNA (Lee et al., 1998; Hande et al., 1999; Herrera et al., 1999).”
BackgroundNucleolar Localization of hTERT Protein Is Associated with Telomerase Function
Yang, Y., Chen, Y., Zhang, C., Huang, H., & Weissman, S. M. (2002) · Experimental Cell Research · doi:10.1006/excr.2002.5541 · Cited by 117
Telomeres, Telomerase and Ageing
Saretzki, G. C. (2018) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-981-13-2835-0_9 · Cited by 120
Alternative Lengthening of Telomeres in Human Cells
Reddel, R. R., Bryan, T. M., Colgin, L. M., Perrem, K., & Yeager, T. R. (2001) · Radiation Research · doi:10.1667/0033-7587(2001)155[0194:alotih]2.0.co;2 · Cited by 109
“that are null for the telomerase RNA gene and have no detectable telomerase activity (14).”
BackgroundLiu, L., Blasco, M. A., & Keefe, D. L. (2002) · EMBO Reports · doi:10.1093/embo-reports/kvf055 · Cited by 102
“Accordingly, we used the absence of a telomere fluorescence signal on a chromosome end as an indicator of telomere dysfunction (Blasco et al., 1997; Hande et al., 1999; Hemann et al., 2001).”
Self-citationYeast Nhp6A/B and Mammalian Hmgb1 Facilitate the Maintenance of Genome Stability
Giavara, S., Kosmidou, E., Hande, M. P., Bianchi, M. E., Morgan, A., di Fagagna, F. D., & Jackson, S. P. (2005) · Current Biology · doi:10.1016/j.cub.2004.12.065 · Cited by 100
Self-citationOpitz, O. G., Suliman, Y., Hahn, W. C., Harada, H., Blum, H. E., & Rustgi, A. K. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11909 · Cited by 101
“Telomere shortening in cells from telomerase-deficient mice results in loss of telomere function and consequently genetic instability with chromosomal end-toend fusions (47).”
BackgroundBreaks at telomeres and TRF2-independent end fusions in Fanconi anemia
Callén, E. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.4.439 · Cited by 98
“The relationship between telomere length and chromosome fusions in mammalian cells became evident in telomerase-deficient mice with short telomeres where a high frequency of Robertsonian fusions was observed (8,27).”
FISH characterization of a dicentric Yq (p11.32) isochromosome in an azoospermic male
Codina-Pascual, M., Oliver‐Bonet, M., Navarro, J., Starke, H., Liehr, T., Gutiérrez-Mateo, C., Sánchez-García, J. F., Arango, O., Egozcue, J., & Benet, J. (2004) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.30027 · Cited by 98
“By using the PNA-telomere probe [Hande et al., 1999] no interstitial telomeric signals were detected, although the probe hybridized to the Yq telomeric sequences (Fig.”
MethodZhang, M., Bener, M. B., Jiang, Z., Wang, T., Esencan, E., Scott, R., Horváth, T. L., & Seli, E. U. (2019) · Aging · doi:10.18632/aging.102024 · Cited by 99
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 96
“Indeed, these cells were shown to stabilize or elongate their telomeres and to accumulate numerous fusions and translocations (Hande et al., 1999a), indicating that continued cell culture in the absence of telomerase is a potent inducer of chromosomal instability, a key event in cellular…”
BackgroundInfluentialSelf-citationReconstructing 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
“The average telomere length decreases nonlinearly in the presence of symmetric stem cell self-renewal The average telomere length decreases in most human tissues with age (Harley et al., 1990).”
The shortest telomeres drive karyotype evolution in transformed cells
Der‐Sarkissian, H., Bacchetti, S., Cazes, L., & Londoño‐Vallejo, A. (2004) · Oncogene · doi:10.1038/sj.onc.1207152 · Cited by 97
“…data in the literature support a correlation between exaggerated shortening and telomere dysfunction (Counter et al., 1992; Blasco et al., 1997; Hande et al., 1999; Gisselsson et al., 2001; Hackett et al., 2001), this relationship has never been directly shown for specific chromosome…”
BackgroundGuiducci, C., Cerone, M. A., & Bacchetti, S. (2001) · Oncogene · doi:10.1038/sj.onc.1204145 · Cited by 94
Brümmendorf, T. H., & Balabanov, S. (2006) · Leukemia · doi:10.1038/sj.leu.2404339 · Cited by 95
The significance of telomerase activation and cellular immortalization in human cancer
Newbold, R. F. (2002) · Mutagenesis · doi:10.1093/mutage/17.6.539 · Cited by 94
“Hande et al. (1999) shed some light on this conundrum by showing that, in immortal cells from telomerase-null mice, telomere length became stabilized in a chromosome-specific manner, indicating that a telomerase-independent telomere maintenance mechanism can be activated in mouse cells.”
BackgroundPreferential maintenance of critically short telomeres in mammalian cells heterozygous for mTert
Liu, Y., Kha, H. T., Ungrin, M., Robinson, M. O., & Harrington, L. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.062549199 · Cited by 94
Accelerated Telomere Shortening in the Human Inactive X Chromosome
Surrallés, J., Hande, M. P., Marcos, R., & Lansdorp, P. M. (1999) · The American Journal of Human Genetics · doi:10.1086/302665 · Cited by 92
“Telomeres are known to play a key role in chromosome segregation (Sandell and Zakian 1993; Blasco et al. 1997; Kirk et al. 1997; Hande et al. 1999).”
BackgroundSelf-citationAutophagy, Cellular Aging and Age-related Human Diseases
Cheon, S. Y., Kim, H. J., Rubinsztein, D. C., & Lee, J. E. (2019) · Experimental Neurobiology · doi:10.5607/en.2019.28.6.643 · Cited by 95
“Also, chromosomal instability increases in fibroblasts derived from older telomerase (mouse transferase RNA, mTER)-null mice that have compromised telomerase activity [83].”
BackgroundAneuploidy in Cancer: Seq-ing Answers to Old Questions
Knouse, K. A., Davoli, T., Elledge, S. J., & Amon, A. (2016) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-042616-072231 · Cited by 87
“F or p er so na l u se o nl y. Acentric chromosome: a chromosome lacking a centromere Dicentric chromosome: a chromosome with two centromeres produce acentric or dicentric chromosomes that can attach improperly to the mitotic spindle and missegregate (Burrell et al. 2013, Hande et al. 1999).”
BackgroundBull, C. F., & Fenech, M. F. (2008) · Proceedings of The Nutrition Society · doi:10.1017/s0029665108006988 · Cited by 91
“Degradation of telomeres has been shown to lead to whole chromosomal instability, via telomere end fusion, and the generation of breakage–fusion–bridge cycles within chromosomes, which leads to gene amplification and gene dosage imbalance, an important risk factor for cancer (53–55) .”
Lo, A. W. I., Sprung, C. N., Fouladi, B., Pedram, M., Sabatier, L., Ricoul, M., Reynolds, G. E., & Murnane, J. P. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.13.4836-4850.2002 · Cited by 118
“Increased chromosome fusion and chromosome instability has been observed in cells from telomerasedeficient mice ( 27 ) and in mammalian cells with a variety of mutations that affect telomere function, including DNA-PKcs (4, 24), Ku (4, 31), and TRF2 (79).”
BackgroundChromatin regulation and non-coding RNAs at mammalian telomeres
Schoeftner, S., & Blasco, M. A. (2009) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2009.09.015 · Cited by 96
Self-citationTelomeric Protein Distributions and Remodeling Through the Cell Cycle inSaccharomyces cerevisiae
Smith, C. D., Smith, D. L., DeRisi, J. L., & Blackburn, E. H. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-08-0457 · Cited by 89
“Vol. 14, 556–570, February 2003”
BackgroundRepair of telomeric DNA prior to replicative senescence
Lansdorp, P. M. (2000) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(00)00151-2 · Cited by 87
Self-citation
Metadata
- Authors
- Hande, M. P., Samper, E., Lansdorp, P., & Blasco, M. A.
- Affiliations
- University of British Columbia (CA)
- *Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Campus Cantoblanco, Madrid E-28049, Spain; ‡Terry Fox Laboratory, British Columbia Cancer Research Center, Vancouver, British Columbia V5Z 1L3, Canada; and §Department of Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 1999-02-22
- Volume
- 144
- Issue
- 4
- Pages
- 589-601
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2132934
- OpenAlex
- W2110286112
- Cited by
- 313
- References
- 63
- Citations by year
- 2026: 1 · 2024: 5 · 2023: 1 · 2020: 1 · 2019: 6 · 2018: 7 · 2017: 5 · 2016: 10 · 2015: 8 · 2014: 8 · 2013: 10 · 2012: 7
- FWCI
- 16.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1r01gm056162-01)
- National Cancer Institute (P01CA013106)
- National Institute of General Medical Sciences (GM56162)
- National Institute of Allergy and Infectious Diseases (R01AI029524)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Keywords
- telomere length, chromosomal instability, telomerase RNA, telomere shortening, chromosome 2, chromosome 11, translocation, cell immortalization, fibroblasts, tumor formation, telomere maintenance
- MeSH terms
- Animals, Cell Transformation, Neoplastic, Cells, Cultured, Chromosome Aberrations, Models, Genetic, Neoplasms, Experimental, Telomere, In Situ Hybridization, Fluorescence, Mice, Knockout, Telomerase, Mice
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