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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
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“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×
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Items 101–200 of 313
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 90
Self-citationTelomeres: Implications for Cancer Development
Bernal, A., & Tusell, L. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19010294 · Cited by 92
“Cytogenetic analysis of telomerase deficient cells after successive intercrossing of mTerc−/− animals showed an increase in end-to-end chromosome fusions, NTRs, and aneuploidy [134,136].”
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“Telomere loss is associated with end-to-end fusion and more generalized chromosomal instability (Muller, 1938; McClintock, 1941; Ducray et al., 1999; Hande et al., 1999; Artandi and DePinho, 2000).”
BackgroundDo tumor-suppressive mechanisms contribute to organism aging by inducing stem cell senescence?
Pelicci, P. G. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20750 · Cited by 86
Cloning to reproduce desired genotypes
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Telomere elongation (Tel), a New Mutation in Drosophila melanogaster That Produces Long Telomeres
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Brümmendorf, T. H., Rufer, N., Holyoake, T. L., MACIEJEWSKI, J., BARNETT, M. J., Eaves, C. J., Eaves, A. C., Young, N. S., & Lansdorp, P. M. (2001) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2001.tb03598.x · Cited by 83
Self-citationQuantitative Fluorescence In Situ Hybridization (Q‐FISH)
Poon, S. S. S., & Lansdorp, P. M. (2001) · Current Protocols in Cell Biology · doi:10.1002/0471143030.cb1804s12 · Cited by 82
Self-citationA Dual Role of p21 in Stem Cell Aging
Ju, Z., Choudhury, A. R., & Rudolph, K. L. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1395.036 · Cited by 84
Tet Enzymes Regulate Telomere Maintenance and Chromosomal Stability of Mouse ESCs
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“Telomere QFISH Telomere length and function (telomere integrity and chromosome stability) was estimated by telomere QFISH (Hande et al., 1999; Herrera et al., 1999; Huang et al., 2011; Poon et al., 1999; Zijlmans et al., 1997).”
A 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 79
Self-citationChromosomal aberrations involving telomeres and interstitial telomeric sequences
Bolzán, A. D. (2011) · Mutagenesis · doi:10.1093/mutage/ger052 · Cited by 78
Palanca-Wessels, M. C., Klingelhutz, A. J., Reid, B. J., Norwood, T. H., Opheim, K. E., Paulson, T. G., Feng, Z., & Rabinovitch, P. S. (2003) · Carcinogenesis · doi:10.1093/carcin/bgg076 · Cited by 75
Nagele, R. G., Velasco, A. Q., Anderson, W. J., McMahon, D. J., Thomson, Z., Fazekas, J., Kitson-Wind, K., & Lee, H. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.2.377 · Cited by 74
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
McNees, C. J., Tejera, Á. M., Martínez, P., Murga, M., Mulero, F., Fernández-Capetillo, Ó., & Blasco, M. A. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.200908136 · Cited by 71
“…it has been found to have a shorter mean telomere length than other mouse chromosomes in several independent mouse strains (Zijlmans et al., 1997; Hande et al., 1999; Samper et al., 2001a), whereas chromosome 11 was chosen because it is homologous to human chromosome 17, which was also reported…”
Self-citationO’Callaghan, N. J., Clifton, P. M., Noakes, M., & Fenech, M. F. (2009) · Rejuvenation Research · doi:10.1089/rej.2008.0819 · Cited by 72
Telomeres, telomerase, and cancer: life on the edge of genomic stability
Oulton, R., & Harrington, L. A. (2000) · Current Opinion in Oncology · doi:10.1097/00001622-200001000-00013 · Cited by 71
Liu, J., & Li, H. (2010) · Reproduction · doi:10.1530/rep-10-0008 · Cited by 71
“1997, Hande et al .”
Telomere elongation chooses TERRA ALTernatives
Arora, R., & Azzalin, C. M. (2015) · RNA Biology · doi:10.1080/15476286.2015.1065374 · Cited by 73
Pampalona, J., Soler, D., Genescà, A., & Tusell, L. (2009) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2009.10.001 · Cited by 69
Denham, J., O’Brien, B. J., Prestes, P. R., Brown, N. J., & Charchar, F. J. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00587.2015 · Cited by 72
“3 Introduction 51 Telomeres are repetitive DNA (in mammals, 5’-TTAGGG-3’) positioned at the ends 52 of chromosomes that protect against genomic DNA degradation and chromosomal 53 fusion events (24, 25).”
BackgroundTelomere content correlates with stage and prognosis in breast cancer
Fordyce, C., Heaphy, C. M., Bisoffi, M., Wyaco, J. L., Joste, N. E., Mangalik, A., Baumgartner, K. B., Baumgartner, R., Hunt, W. C., & Griffith, J. K. (2006) · Breast Cancer Research and Treatment · doi:10.1007/s10549-006-9204-1 · Cited by 69
The Mre11 Complex and the Response to Dysfunctional Telomeres
Attwooll, C. L., Akpınar, M., & Petrini, J. H. J. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00479-09 · Cited by 66
“levels (cPDLs) were calculated using the formula PDL log(nf/no)/log(2), where no is the initial number of cells and nf is the final number of cells (16).”
MethodChromosome instability in neoplasia: chaotic roots to continuous growth
Gagos, S., & Irminger‐Finger, I. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.01.003 · Cited by 64
DNA repair factors and telomere-chromosome integrity in mammalian cells
Hande, M. P. (2004) · Cytogenetic and Genome Research · doi:10.1159/000077475 · Cited by 64
“However, embryonic fibroblasts obtained from mTER–/– (mouse telomerase RNA; telomerase negative) mice could be immortalized in vitro and displayed telomere maintenance with associated chromosomal defects at later passages in culture (Hande et al., 1999a).”
BackgroundInfluentialSelf-citationSpeel, E. M. (1999) · Histochemistry and Cell Biology · doi:10.1007/s004180050396 · Cited by 65
Telomeres, senescence, and hematopoietic stem cells
Zimmermann, S., & Martens, U. M. (2007) · Cell and Tissue Research · doi:10.1007/s00441-007-0469-4 · Cited by 66
“In the following generations, cytogenetic aberrations, a comprised BM, immune deficiency, tumor formation, and an overall reduced lifespan appear, as in DKC patients (Blasco et al. 1997; Hande et al. 1999; Herrera et al. 1999; Rudolph et al. 1999).”
BackgroundPennaneach, V., & Kolodner, R. D. (2004) · Nature Genetics · doi:10.1038/ng1359 · Cited by 65
“tel1∆ rad55∆ 87 (25) 5212 661 (188) 5220 ND ND”
Vespa, L., Couvillion, M., Spangler, E. A., & Shippen, D. E. (2005) · Genes & Development · doi:10.1101/gad.1333805 · Cited by 63
“Bridged anaphase chromosomes are a hallmark of dysfunctional telomeres, reflecting the formation of dicentric chromosomes that arise from fusion of deprotected chromosome ends (Hande et al. 1999; Artandi et al. 2000).”
BackgroundElse, T., Trovato, A., Kim, A. C., Wu, Y., Ferguson, D. O., Kuick, R. D., Lucas, P. C., & Hammer, G. D. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.04.011 · Cited by 62
“Furthermore, a hallmark of telomere dysfunction in Terc / mice is the presence of chromosomal fusions lacking telomere signals at the fusion site (Hande et al., 1999).”
BackgroundInfluentialChromosomal instability—mechanisms and consequences
Venkatesan, S., Natarajan, A. T., & Hande, M. P. (2015) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2015.08.008 · Cited by 62
Self-citationH2AX regulates meiotic telomere clustering
Fernández-Capetillo, Ó., Liebe, B., Scherthan, H., & Nussenzweig, A. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200305124 · Cited by 60
“…gy Telomeres of H2AX-deficient mice | Fernandez-Capetillo et al. 19 Analysis of telomere lengths and fusions Quantitative FISH analysis using a Cy3-labeled (CCCTAA) peptide nucleic acid probe (Applied Biosystems) was performed as described previously (Zijlmans et al., 1997; Hande et al., 1999).”
MethodResultInfluentialMeasurements of telomere length on individual chromosomes by image cytometry
Poon, S. S. S., & Lansdorp, P. M. (2001) · Methods in cell biology · doi:10.1016/s0091-679x(01)64007-x · Cited by 60
Self-citationInduction of a p95/Nbs1‐mediated S phase checkpoint by telomere 3′ overhang specific DNA
Eller, M. S., Li, G., Firoozabadi, R., Puri, N., & Gilchrest, B. A. (2003) · The FASEB Journal · doi:10.1096/fj.02-0197com · Cited by 59
Role of Human Ku86 in Telomere Length Maintenance and Telomere Capping
Jaco, I., Muñoz, P., & Blasco, M. A. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-1381 · Cited by 60
“In particular, whereas end-to-end fusions of human chromosomes are very unstable, end-to-end fusions of mouse chromosomes are stably transmitted in culture (36).”
BackgroundSelf-citationLe, R., Kou, Z., Jiang, Y., Li, M., Huang, B. S., Liu, W., Li, H., Kou, X., He, W., Rudolph, K. L., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.11.005 · Cited by 58
“Telomeres play key roles in maintaining chromosome stability and cell replicative capacity (d’Adda di Fagagna et al., 2003; Hande et al., 1999).”
BackgroundRearrangements of ribosomal DNA clusters in late generation telomerase-deficient Arabidopsis
Široký, J., Žlůvová, J., Říha, K., Shippen, D. E., & Vyskot, B. (2003) · Chromosoma · doi:10.1007/s00412-003-0251-7 · Cited by 57
“high frequency of chromosome end-to-end fusions in late generation mTR / mice (Blasco et al. 1997; Hande et al. 1999).”
BackgroundSaccharomyces cerevisiae as a Model System To Define the Chromosomal Instability Phenotype
Putnam, C. D., Pennaneach, V., & Kolodner, R. D. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.16.7226-7238.2005 · Cited by 55
“These products can comigrate to the same pole during mitosis (38, 87, 102), inactivate one of the centromeres (2, 12, 32, 39, 102), or undergo additional cycles of rearrangements during mitosis (59, 60, 65, 67).”
BackgroundEquine telomeres and telomerase in cellular immortalisation and ageing
Argyle, D. J., Ellsmore, V., Gault, E. A., Munro, A. F., & Nasir, L. (2003) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(03)00104-0 · Cited by 56
“Telomere and telomerase biology has been assessed in a number of mammalian species including human, mouse, non-human primate, and dog (Harley et al., 1990; Vaziri et al., 1994; Chang and Harley, 1995; Hande et al., 1999; Nasir et al., 2001; Steinert et al., 2002).”
BackgroundHong, J.-P., Byun, M. Y., Koo, D., An, K., Bang, J.-W., Chung, I. K., An, G., & Kim, W. T. (2007) · The Plant Cell · doi:10.1105/tpc.107.051953 · Cited by 55
“Bars ¼ 5 mM. the fusion of unprotected chromosome termini due to structural defects of telomeres (Hande et al., 1999; Artandi et al., 2000).”
Immunosenescence phenotypes in the telomerase knockout mouse
Blasco, M. A. (2002) · Springer Seminars in Immunopathology · doi:10.1007/s00281-001-0096-1 · Cited by 57
“Interestingly, telomerase-independent telomere elongation or alternative lengthening of telomeres (ALT) has been described in immortal human cell lines that do not have detectable telomerase activity [12, 13], as well as in cell lines derived from telomerase-deficient mice [27].”
BackgroundResultSelf-citationO’Callaghan, N. J., Baack, N., Sharif, R., & Fenech, M. F. (2011) · BioTechniques · doi:10.2144/000113788 · Cited by 56
Mastromonaco, G. F., Perrault, S. D., Betts, D. H., & King, W. A. (2006) · BMC Developmental Biology · doi:10.1186/1471-213x-6-41 · Cited by 53
Mammalian telomeres and their partnership with lamins
Burla, R., Torre, M. L., & Saggio, I. (2016) · Nucleus · doi:10.1080/19491034.2016.1179409 · Cited by 58
Telomere and Telomerase Modulation by the Mammalian Rad9/Rad1/Hus1 DNA-Damage-Checkpoint Complex
Francia, S., Weiss, R. S., Hande, M. P., Freire, R., & di Fagagna, F. D. (2006) · Current Biology · doi:10.1016/j.cub.2006.06.066 · Cited by 53
Self-citationTelomerase: Dr Jekyll or Mr Hyde?
Prescott, J. C., & Blackburn, E. H. (1999) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)80055-0 · Cited by 52
Schwartz, J. L., Jordan, R. T., Liber, H. L., Murnane, J. P., & Evans, H. H. (2001) · Genes Chromosomes and Cancer · doi:10.1002/1098-2264(2000)9999:9999 · Cited by 27
Self-citation2009 Nobel Prize in Physiology or Medicine: telomeres and telomerase
Varela, E., & Blasco, M. A. (2010) · Oncogene · doi:10.1038/onc.2010.15 · Cited by 53
“Nonetheless, primary cells from telomerase-deficient mice can also form tumors, maintaining their telomere length by recombinational mechanisms (Blasco, 2007; Hande et al., 1999; Herrera et al., 2000; Morrish and Greider, 2009).”
BackgroundSelf-citationN–nitrosamines are associated with shorter telomere length
Li, H., Jönsson, B., Lindh, C. H., Albin, M. C., & Bröberg, K. (2011) · Scandinavian Journal of Work Environment & Health · doi:10.5271/sjweh.3150 · Cited by 49
Targeting DNA-PKcs and telomerase in brain tumour cells
Gurung, R. L., Lim, H. K., Venkatesan, S., Lee, P. S. W., & Hande, M. P. (2014) · Molecular Cancer · doi:10.1186/1476-4598-13-232 · Cited by 49
“Fluorescence in situ hybridisation (FISH) was performed using telomere sequence-specific peptide nucleic acid (PNA) probe labelled with Cy3 as described [44,45].”
MethodSelf-citationBiomarkers of Ionizing Radiation Exposure: A Multiparametric Approach
Zeegers, D., Venkatesan, S., Koh, S. W., Low, G. K. M., Srivastava, P., Sundaram, N., Sethu, S., Banerjee, B., Jayapal, M., Belyakov, O. V., et al. (2017) · Genome Integrity · doi:10.4103/2041-9414.198911 · Cited by 51
Self-citationCanela, A., Klatt, P., & Blasco, M. A. (2007) · Methods in molecular biology · doi:10.1007/978-1-59745-361-5_5 · Cited by 50
Self-citationPrescott, J. C., & Blackburn, E. H. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.8.2941-2948.2000 · Cited by 51
“However, such critically short telomeres still contain substantial tracts of telomeric repeat DNA (15).”
BackgroundO’Callaghan, N. J., Toden, S., Bird, A. R., Topping, D. L., Fenech, M. F., & Conlon, M. A. (2011) · Clinical Nutrition · doi:10.1016/j.clnu.2011.09.003 · Cited by 50
Tichy, E. D., Sidibe, D. K., Tierney, M. T., Stec, M. J., Sharifi‐Sanjani, M., Hosalkar, H. S., Mubarak, S. J., Johnson, F. B., Sacco, A., & Mourkioti, F. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.08.003 · Cited by 49
“Historically, cells are treated with microtubule inhibitors to promote metaphase arrest, after which metaphase spreads are stained and analyzed (Hande et al., 1999).”
BackgroundMethodTELOMERE SHORTENING IN A LONG-LIVED MARINE BIRD: CROSS-SECTIONAL ANALYSIS AND TEST OF AN AGING TOOL
Juola, F. A., Haussmann, M. F., Dearborn, D. C., & Vleck, C. M. (2006) · The Auk · doi:10.1093/auk/123.3.775 · Cited by 49
Centromere fission, not telomere erosion, triggers chromosomal instability in human carcinomas
Martínez‐A, C., & van Wely, K. H. M. (2011) · Carcinogenesis · doi:10.1093/carcin/bgr069 · Cited by 49
“chromosome end-to-end fusions (49), this neither reproduces the CIN phenotype nor”
BackgroundTelomere‐mediated genomic instability and the clinico‐pathological parameters in breast cancer
Poonepalli, A., Banerjee, B., Ramnarayanan, K., Palanisamy, N., Putti, T. C., & Hande, M. P. (2008) · Genes Chromosomes and Cancer · doi:10.1002/gcc.20608 · Cited by 45
“The tissue sections were then hybridized with Cy3 conjugated PNA telomere probe (Applied Biosystems, Boston, MA) for 2 hr at room temperature after co-denaturation at 808C for 3 min (Hande et al., 1999).”
MethodSelf-citationReduction of telomerase activity in human liver cancer cells by a histone deacetylase inhibitor
Nakamura, M., Saito, H., Ebinuma, H., Wakabayashi, K., Saito, Y., Takagi, T., Nakamoto, N., & Ishii, H. (2001) · Journal of Cellular Physiology · doi:10.1002/jcp.1087 · Cited by 44
“Loss of telomeric repeats eventually limits the number of cell divisions when only a critical small number remains (Blackburn, 1991; Hande et al., 1999).”
BackgroundIdentification of telomere-dependent "senescence-like" arrest in mouse embryonic fibroblasts.
Espejel, S., & Blasco, M. (2002) · Experimental Cell Research · doi:10.1006/excr.2002.5533 · Cited by 47
Self-citationG-Quadruplexes as Potential Therapeutic Targets for Embryonal Tumors
Shalaby, T., Fiaschetti, G., Nagasawa, K., Shin‐ya, K., Baumgartner, M., & Grotzer, M. A. (2013) · Molecules · doi:10.3390/molecules181012500 · Cited by 46
“In this scenario, as telomeres shorten with each cell cycle the “sticky” ends of chromosomes become prone to fusions [100] leading to subsequent chromosomal instability [100–103] and offering a mechanism for a continuous rearrangement of chromosome structure that might contribute to oncogene amplification and tumor su…”
BackgroundShort dysfunctional telomeres impair the repair of arsenite‐induced oxidative damage in mouse cells
Newman, J. P. A., Banerjee, B., Fang, W., Poonepalli, A., Balakrishnan, L., Low, G. K. M., Bhattacharjee, R. N., Akira, S., Jayapal, M., Melendez, A. J., et al. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21276 · Cited by 43
“L I S S , I N C . structures constitute the final 12–80 kb of all mouse chromosomes (Zijlmans et al., 1997; Hande et al., 1999).”
BackgroundMethodResultInfluentialSelf-citationTelomeric sequences, radiation sensitivity and genomic instability
Bouffler, S. D., Blasco, M. A., Cox, R., & Smith, P. J. (2001) · International Journal of Radiation Biology · doi:10.1080/09553000110069326 · Cited by 43
“The gene product defective in A-T,(Bailey et al. 1999, Hande et al. 1999b, Goytisolo et al. 2001) , Ku-de cient cells (Hsu et al. 2000, Samper ATM, has been implicated in many cellular pathways including mitogenic signal transduction, chromosomeet al. 2000) and cells from Werner’s syndrome…”
BackgroundSelf-citationRecent advances in the development of telomerase inhibitors for the treatment of cancer
Perry, P. J., & Jenkins, T. C. (1999) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.8.12.1981 · Cited by 42
Bernard, L., Bélisle, C., Mollica, L. R., Provost, S., Roy, D.-C., Gilliland, D. G., Levine, R. L., & Busque, L. (2008) · Leukemia · doi:10.1038/leu.2008.319 · Cited by 40
MST-312 Alters Telomere Dynamics, Gene Expression Profiles and Growth in Human Breast Cancer Cells
Gurung, R. L., Lim, S. N., Low, G. K. M., & Hande, M. P. (2014) · Lifestyle Genomics · doi:10.1159/000381346 · Cited by 39
Self-citationTelomere shortening and cell fates in mouse models of neoplasia
Artandi, S. E. (2002) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(01)02222-5 · Cited by 40
Plasma micronutrient levels and telomere length in children
Milne, E., O’Callaghan, N. J., Ramankutty, P., de Klerk, N. H., Greenop, K. R., Armstrong, B. K., Miller, M., & Fenech, M. F. (2014) · Nutrition · doi:10.1016/j.nut.2014.08.005 · Cited by 39
Parolini, M., Romanò, A., Khoriauli, L., Nergadze, S. G., Caprioli, M., Rubolini, D., Santagostino, M., Saino, N., & Giulotto, E. (2015) · PLoS ONE · doi:10.1371/journal.pone.0142530 · Cited by 39
SIRT6 participates in the quality control of aged oocytes via modulating telomere function
Ge, J., Li, C., Li, C., Huang, Z., Zeng, J., Han, L., & Wang, Q. (2019) · Aging · doi:10.18632/aging.101885 · Cited by 42
“com 1966 AGING that telomeres serve multiple functions in protecting the ends of chromosomes from degradation and preventing illegitimate chromosomal recombination [15, 16].”
BackgroundTelomerase-dependent and -independent chromosome healing in mouse embryonic stem cells
Gao, Q., Reynolds, G. E., Wilcox, A., Miller, D. L., Cheung, P., Artandi, S. E., & Murnane, J. P. (2008) · DNA repair · doi:10.1016/j.dnarep.2008.04.004 · Cited by 38
“The 10PTKOES cell line is therefore typical of other mouse embryonic broblasts and ES cell line that maintain telomeres through a elomerase-independent mechanism, which also contain very hort telomeres [47,50].”
BackgroundBouffler, S. D., Haines, J. W., Edwards, A. A., Harrison, J. D., & Cox, R. (2001) · Radiation Research · doi:10.1667/0033-7587(2001)155[0345:lodtci]2.0.co;2 · Cited by 39
Telomeres and Telomerase in Stem Cells during Aging and Disease
Ju, Z., & Rudolph, K. L. (2006) · KARGER eBooks · doi:10.1159/000092502 · Cited by 39
Telomere length regulation during cloning, embryogenesis and ageing
Schaetzlein, S., & Rudolph, K. L. (2004) · Reproduction Fertility and Development · doi:10.1071/rd04112 · Cited by 38
“(Counter et al. 1992; Blasco et al. 1997a; Hande et al. 1999).”
Szafarowska, M., & Jerzak, M. M. (2013) · Ginekologia Polska · doi:10.17772/gp/1580 · Cited by 38
“Krytyczne skrócenie telomerów powoduje zatrzymanie podziałów komórkowych, niestabilność genetyczną oraz wyzwala proces apoptozy [46].”
Slatter, T. L., Gifford-Garner, J., Wiles, A. K., Tan, X., Chen, Y.-J., MacFarlane, M. R., Sullivan, M. J., Royds, J. A., & Hung, N. A. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.100468 · Cited by 38
Association of BLM and BRCA1 during Telomere Maintenance in ALT Cells
Acharya, S. K., Kaul, Z., Gocha, A. R. S., Martinez, A. R., Harris, J. M., Parvin, J. D., & Groden, J. L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103819 · Cited by 40
Boklan, J., Nanjangud, G. J., MacKenzie, K. L., May, C., Sadelain, M., & Moore, M. A. S. (2002) · PubMed · Cited by 37
Sachsinger, J., González‐Suárez, E., Samper, E., Heicappell, R., Müller, M., & Blasco, M. A. (2001) · PubMed · Cited by 36
Self-citationKhaw, A. K., Silasudjana, M., Banerjee, B., Suzuki, M., Baskar, R., & Hande, M. P. (2007) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2007.06.005 · Cited by 36
Self-citationUHRF1 is a genome caretaker that facilitates the DNA damage response to γ-irradiation
Mistry, H. S., Tamblyn, L., Butt, H., Sisgoreo, D., Gracias, A., Larin, M., Gopalakrishnan, K., Hande, M. P., & McPherson, J. P. (2010) · Genome Integrity · doi:10.1186/2041-9414-1-7 · Cited by 39
“FISH and its subsequent analysis were performed as described before [23].”
Self-citationHigh incidence of rapid telomere loss in telomerase-deficient Caenorhabditis elegans
Cheung, I. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkj417 · Cited by 36
A Near-Infrared Fluorogenic Pyrrole–Imidazole Polyamide Probe for Live-Cell Imaging of Telomeres
Tsubono, Y., Kawamoto, Y., Hidaka, T., Pandian, G. N., Hashiya, K., Bando, T., & Sugiyama, H. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.0c04955 · Cited by 35
Unwinding protein complexes in ALTernative telomere maintenance
Bhattacharyya, S., Sandy, A., & Groden, J. L. (2009) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22388 · Cited by 37
“In other human tumors, immortalized human cell lines and telomerase-null mouse cell lines [Bryan et al., 1995, 1997; Hande et al., 1999; Niida et al., 2000], telomere lengths are maintained through many population doublings (PDs) using one or more non-telomerase mechanisms known as Alternative Lengthening of Telomeres…”
BackgroundAneuploidy, stem cells and cancer
Pathak, S., & Multani, A. S. (2006) · Birkhäuser-Verlag eBooks · doi:10.1007/3-7643-7378-4_3 · Cited by 35
Cloning and transgenesis in mammals: Implications for xenotransplantation
Piedrahita, J. A., & Mir, B. (2004) · American Journal of Transplantation · doi:10.1111/j.1600-6135.2004.0344.x · Cited by 34
“2% for the four different clones tested (19).”
BackgroundMcMurray, H. R., & McCance, D. J. (2004) · Journal of Virology · doi:10.1128/jvi.78.11.5698-5706.2004 · Cited by 35
“It has been shown that cells with critically short telomeres have increased levels of end-to-end chromosomal fusions, as well as ring chromosomes, leading to aneuploidy and possibly potentiating cancer development (3, 37, 58, 74, 85, 95, 105).”
BackgroundMitotic instability associated with late genomic changes in bone and soft tissue tumours
Gisselsson, D., Pålsson, E., Yu, C., Mertens, F., & Mandahl, N. (2003) · Cancer Letters · doi:10.1016/j.canlet.2003.10.022 · Cited by 32
“Benign lesions 1 46, XX [30] 2 46, XY [30] 3 46, XX [30] 4 46, XY [30] 5 46, XX [30] 6 47, XY, þ5 [3]/46, XY [21] 7 46, XX, t(1;11)(p13;q11 2 12) [11]/46, XX [9]”
BackgroundSpanoudakis, E., Bazdiara, I., Pantelidou, D., Kotsianidis, Ι., Papadopoulos, V. P., Margaritis, D., Xanthopoulidis, G., Moustakidis, E., Mantzourani, S., Bourikas, G., et al. (2010) · Leukemia Research · doi:10.1016/j.leukres.2010.07.042 · Cited by 31
“Human telomeres are structures of tandem (5′-TTAGGG-3′)n epeats, capping chromosome ends in association with various roteins [1].”
BackgroundPadhi, S., Saha, A., Kar, M., Ghosh, C., Adhya, A. K., Baisakh, M. R., Mohapatra, N., Venkatesan, S., Hande, M. P., & Banerjee, B. (2015) · Journal of Cancer · doi:10.7150/jca.9558 · Cited by 31
“[41, 42] With increasing histological grades, DNA damage is expected to be higher coupled with the loss of telomere length as compared to the lower grades thus indicating genomic instability and dedifferentiation.”
Self-citationWang, X., Liu, L., Montagna, C., Ried, T., & Deng, C.-X. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402105 · Cited by 31
“Telomere Q-FISH with a telomere probe was performed on chromosome spreads, as described previously.(38) Telomeres were denatured at 801C for 3 min and hybridized with Cy3-labeled (CCCTAA)3 peptide nucleic acid probe (DAKO Corporation, Capinteria, USA), washed and mounted in Vectashield mounting medium mixed with 0.”
MethodShiraishi, H., Mikami, T., Aida, J., Nakamura, K., Izumiyama‐Shimomura, N., Arai, T., Watanabe, M., Okayasu, I., & Takubo, K. (2009) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365520902718705 · Cited by 31
“In addition, the telomere serves as a protective cap on the end of the chromosome [10], and its shortening results in chromosomal instability [11,12].”
Telomerase expression and telomere length in immortal leukocyte lines from channel catfish
Barker, K. S., Quiniou, S. M. A., Wilson, M. R., Bengtén, E., Stuge, T. B., Warr, G. W., Clem, L. W., & Miller, N. W. (2000) · Developmental & Comparative Immunology · doi:10.1016/s0145-305x(00)00021-5 · Cited by 31
Modeling aging and cancer in the telomerase knockout mouse
Chang, S. S. (2005) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2004.08.020 · Cited by 32
Dual roles of telomere dysfunction in initiation and suppression of tumorigenesis
Cosme‐Blanco, W., & Chang, S. S. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.03.011 · Cited by 31
“Increased telomere loss leads to the formation of complex cytogenetic rearrangements, including dicentric chromosomes and the generation of NRTs (reviewed in Maser and DePinho, 2002; Hande et al., 1999; Artandi et Exp Cell Res.”
BackgroundTelomere Dynamics and Homeostasis in a Transmissible Cancer
Újvári, B., Pearse, A., Taylor, R. L., Pyecroft, S., Flanagan, C., Gombert, S., Papenfuss, A. T., Madsen, T. R. L., & Belov, K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044085 · Cited by 29
“In approximately 85% of human cancers, telomerase activity has been shown to facilitate malignant transformation by maintaining replicative potential [29,30].”
BackgroundOrder of genetic events is critical determinant of aberrations in chromosome count and structure
Fauth, C., O’Hare, M. J., Lederer, G., Jat, P., & Speicher, M. R. (2004) · Genes Chromosomes and Cancer · doi:10.1002/gcc.20051 · Cited by 28
“Various authors have addressed the important role of telomerase activity in maintaining chromosomal stability using the telomerase knockout mouse (Blasco et al., 1997; Lee et al., 1998; Hande et al., 1999; Rudolph et al., 1999; Artandi and DePinho, 2000; Artandi et al., 2000; Hemann et al., 2001; Samper et al., 2001;…”
MethodO’Callaghan, N. J., Bull, C. F., & Fenech, M. F. (2013) · The journal of nutrition health & aging · doi:10.1007/s12603-013-0401-4 · Cited by 28
Transient Activation of the ALT Pathway in Human Primary Fibroblasts Exposed to High-LET Radiation
Berardinelli, F., Antoccia, A., Cherubini, R., Nadal, V. D., Gerardi, S., Cirrone, G. A. P., Tanzarella, C., & Sgura, A. (2010) · Radiation Research · doi:10.1667/rr2127.1 · Cited by 29
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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