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Protection of mammalian telomeres
Abstract
Telomeres allow cells to distinguish natural chromosome ends from damaged DNA. When telomere function is disrupted, a potentially lethal DNA damage response can ensue, DNA repair activities threaten the integrity of chromosome ends, and extensive genome instability can arise. It is not clear exactly how the structure of telomere ends differs from sites of DNA damage and how telomeres protect chromosome ends from DNA repair activities. What are the defining structural features of telomeres and through which mechanisms do they ensure chromosome end protection? What is the molecular basis of the telomeric cap and how does it act to sequester the chromosome end? Here I discuss data gathered in the last few years, suggesting that the protection of human chromosome ends primarily depends on the telomeric protein TRF2 and that telomere capping involves the formation of a higher order structure, the telomeric loop or t-loop.
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“In mammalian cells, the ends of the chromosomes consist of a terminal 3′ single-stranded tail, the G strand overhang, which is buried into adjacent double-stranded repetitive telomeric DNA, forming a protective “t loop” higher-order structure (de Lange, 2002”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as de Lange, 2002
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Cites
Mammalian Telomeres End in a Large Duplex Loop
Griffith, J. D., Comeau, L., Rosenfield, S., Stansel, R. M., Bianchi, A., Moss, H., & de Lange, T. (1999) · Cell · doi:10.1016/s0092-8674(00)80760-6 · Cited by 2,447
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
TRF2 Protects Human Telomeres from End-to-End Fusions
van Steensel, B., Smogorzewska, A., & de Lange, T. (1998) · Cell · doi:10.1016/s0092-8674(00)80932-0 · Cited by 1,709
THE STABILITY OF BROKEN ENDS OF CHROMOSOMES IN ZEA MAYS
McClintock, B. (1941) · Genetics · doi:10.1093/genetics/26.2.234 · Cited by 1,605
Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair
Walker, J. R., Corpina, R. A., & Goldberg, J. D. (2001) · Nature · doi:10.1038/35088000 · Cited by 1,216
Di Leonardo, A., Linke, S. P., Clarkin, K., & Wahl, G. M. (1994) · Genes & Development · doi:10.1101/gad.8.21.2540 · Cited by 1,215
p53- and ATM-Dependent Apoptosis Induced by Telomeres Lacking TRF2
Karlseder, J., Broccoli, D., Dai, Y., Hardy, S., & de Lange, T. (1999) · Science · doi:10.1126/science.283.5406.1321 · Cited by 1,086
Inhibition 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
Pot1, the Putative Telomere End-Binding Protein in Fission Yeast and Humans
Baumann, P., & Cech, T. R. (2001) · Science · doi:10.1126/science.1060036 · Cited by 1,028
Chin, 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
Makarov, V. L., Hirose, Y., & Langmore, J. P. (1997) · Cell · doi:10.1016/s0092-8674(00)81908-x · Cited by 959
A mutant with a defect in telomere elongation leads to senescence in yeast
Lundblad, V., & Szostak, J. W. (1989) · Cell · doi:10.1016/0092-8674(89)90132-3 · Cited by 931
Human telomeres contain two distinct Myb–related proteins, TRF1 and TRF2
Broccoli, D., Smogorzewska, A., Chong, L., & de Lange, T. (1997) · Nature Genetics · doi:10.1038/ng1097-231 · Cited by 926
The 3′ to 5′ Exonuclease Activity of Mre11 Facilitates Repair of DNA Double-Strand Breaks
Paull, T. T., & Gellert, M. F. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80097-0 · Cited by 919
Telomerase activity in normal and malignant hematopoietic cells.
Broccoli, D., Young, J. W., & de Lange, T. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9082 · Cited by 754
Normal human chromosomes have long G-rich telomeric overhangs at one endPreprint
Wright, W. E., Tesmer, V. M., Huffman, K. E., Levene, S. D., & Shay, J. W. (1997) · Genes & Development · doi:10.1101/gad.11.21.2801 · Cited by 754
Sherr, C. J., & DePinho, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)00046-5 · Cited by 745
Telomere shortening and apoptosis in telomerase-inhibited human tumor cells
Zhang, X., Mar, V., Zhou, W., Harrington, L., & Robinson, M. O. (1999) · Genes & Development · doi:10.1101/gad.13.18.2388 · Cited by 698
Boulton, S. J., & Jackson, S. P. (1998) · The EMBO Journal · doi:10.1093/emboj/17.6.1819 · Cited by 641
Garvik, B. M., Carson, M., & Hartwell, L. H. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.11.6128 · Cited by 629
Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres
Zhu, X., Küster, B., Mann, M., Petrini, J. H. J., & de Lange, T. (2000) · Nature Genetics · doi:10.1038/77139 · Cited by 619
Li, B., Oestreich, S. C., & de Lange, T. (2000) · Cell · doi:10.1016/s0092-8674(00)80858-2 · Cited by 609
Cdc13p: A Single-Strand Telomeric DNA-Binding Protein with a Dual Role in Yeast Telomere Maintenance
Nugent, C. I., Hughes, T., Lue, N. F., & Lundblad, V. (1996) · Science · doi:10.1126/science.274.5285.249 · Cited by 606
DNA end-joining: from yeast to man
Critchlow, S. E., & Jackson, S. P. (1998) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01284-5 · Cited by 584
Telomeric localization of TRF2, a novel human telobox protein
Bilaud, T., Brun, C., Ancelin, K., Koering, C., Laroche, T., & Gilson, É. (1997) · Nature Genetics · doi:10.1038/ng1097-236 · Cited by 532
Regulation of telomere length and function by a Myb-domain protein in fission yeast
Cooper, J. P., Nimmo, E. R., Allshire, R. C., & Cech, T. R. (1997) · Nature · doi:10.1038/385744a0 · Cited by 503
Robles, S. J., & Adami, G. R. (1998) · Oncogene · doi:10.1038/sj.onc.1201862 · Cited by 498
Yeast Ku as a Regulator of Chromosomal DNA End Structure
Gravel, S., Larrivée, M., Labrecque, P., & Wellinger, R. J. (1998) · Science · doi:10.1126/science.280.5364.741 · Cited by 444
Yeast Checkpoint Genes in DNA Damage Processing: Implications for Repair and Arrest
Lydall, D. A., & Weinert, T. A. (1995) · Science · doi:10.1126/science.270.5241.1488 · Cited by 416
Luo, G., Yao, M. S., Bender, C. F., Mills, M., Bladl, A. R., Bradley, A., & Petrini, J. H. J. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.13.7376 · Cited by 415
Cdc13 Delivers Separate Complexes to the Telomere for End Protection and Replication
Pennock, E., Buckley, K., & Lundblad, V. (2001) · Cell · doi:10.1016/s0092-8674(01)00226-4 · Cited by 414
DNA double-strand break repair proteins are required to cap the ends of mammalian chromosomes
Bailey, S. M., Meyne, J., Chen, D. J., Kurimasa, A., Li, G. C., Lehnert, B. E., & Goodwin, E. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.26.14899 · Cited by 403
A DNA Damage Response Pathway Controlled by Tel1 and the Mre11 Complex
Usui, T., Ogawa, H., & Petrini, J. H. J. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00270-2 · Cited by 384
Telomerase extends the lifespan of virus-transformed human cells without net telomere lengthening
Zhu, J., Wang, H., Bishop, J. M., & Blackburn, E. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.7.3723 · Cited by 382
The terminal DNA structure of mammalian chromosomes
McElligott, R., & Wellinger, R. J. (1997) · The EMBO Journal · doi:10.1093/emboj/16.12.3705 · Cited by 379
Telomere maintenance is dependent on activities required for end repair of double-strand breaks
Nugent, C. I., Bosco, G., Ross, L. O., Evans, S. K., Salinger, A. P., Moore, J. K., Haber, J. E., & Lundblad, V. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70253-2 · Cited by 370
Ku acts in a unique way at the mammalian telomere to prevent end joiningPreprint
Hsu, H.-L., Gilley, D. P., Galande, S., Hande, M. P., Allen, B. L., Kim, S., Li, G. C., Campisi, J., Kohwi-shigematsu, T., & Chen, D. J. (2000) · Genes & Development · doi:10.1101/gad.844000 · Cited by 351
Ku is associated with the telomere in mammals
Hsu, H.-L., Gilley, D. P., Blackburn, E. H., & Chen, D. J. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.22.12454 · Cited by 333
Samper, E., Goytisolo, F. A., Slijepčević, P., van Buul, P. P. W., & Blasco, M. A. (2000) · EMBO Reports · doi:10.1093/embo-reports/kvd051 · Cited by 317
Lin, J., & Zakian, V. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13760 · Cited by 315
Genes involved in senescence and immortalization
Lundberg, A. S., Hahn, W. C., Gupta, P., & Weinberg, R. A. (2000) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00155-1 · Cited by 313
MRT-2 checkpoint protein is required for germline immortality and telomere replication in C. elegans
Ahmed, S. C., & Hodgkin, J. (2000) · Nature · doi:10.1038/35003120 · Cited by 294
d'Adda di Fagagna, F., Hande, M. P., Tong, W.-M., Roth, D., Lansdorp, P. M., Wang, Z.-Q., & Jackson, S. P. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00328-1 · Cited by 293
RAP1: a protean regulator in yeast
Shore, D. (1994) · Trends in Genetics · doi:10.1016/0168-9525(94)90058-2 · Cited by 280
Qi, H., & Zakian, V. A. (2000) · Genes & Development · doi:10.1101/gad.14.14.1777 · Cited by 276
Telomere Shortening Is Proportional to the Size of the G-rich Telomeric 3′-Overhang
Huffman, K. E., Levene, S. D., Tesmer, V. M., Shay, J. W., & Wright, W. E. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002843200 · Cited by 274
Grandin, N., Reed, S. I., & Charbonneau, M. (1997) · Genes & Development · doi:10.1101/gad.11.4.512 · Cited by 264
Strand-Specific Postreplicative Processing of Mammalian Telomeres
Bailey, S. M., Cornforth, M. N., Kurimasa, A., Chen, D. J., & Goodwin, E. H. (2001) · Science · doi:10.1126/science.1062560 · Cited by 257
Grandin, N., Reed, S. I., & Charbonneau, M. (1997) · HAL · Cited by 251
Ten1 functions in telomere end protection and length regulation in association with Stn1 and Cdc13
Grandin, N., Damon‐Soubeyrand, C., & Charbonneau, M. (2001) · The EMBO Journal · doi:10.1093/emboj/20.5.1173 · Cited by 249
Structure of the TRFH Dimerization Domain of the Human Telomeric Proteins TRF1 and TRF2
Fairall, L., Chapman, L., Moss, H., de Lange, T., & Rhodes, D. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00321-5 · Cited by 247
The p53-dependent G1 cell cycle checkpoint pathway and ataxia-telangiectasia.
Canman, C. E., Wolff, A. C., Chen, C.-Y., Fornace, A. J., & Kastan, M. B. (1994) · PubMed · Cited by 246
The function of a stem-loop in telomerase RNA is linked to the DNA repair protein Ku
Peterson, S. E., Stellwagen, A. E., Diede, S. J., Singer, M. S., Haimberger, Z. W., Johnson, C. O., Tzoneva, M., & Gottschling, D. E. (2001) · Nature Genetics · doi:10.1038/83778 · Cited by 232
t‐loops at trypanosome telomeres
Muñoz‐Jordán, J. L., Cross, G., de Lange, T., & Griffith, J. D. (2001) · The EMBO Journal · doi:10.1093/emboj/20.3.579 · Cited by 227
Living 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
Role of T antigen interactions with p53 in tumorigenesis
Pipas, J. M., & Levine, A. J. (2001) · Seminars in Cancer Biology · doi:10.1006/scbi.2000.0343 · Cited by 204
Goytisolo, F. A., Samper, E., Edmonson, S., Taccioli, G. E., & Blasco, M. A. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.11.3642-3651.2001 · Cited by 199
Interaction of human Ku70 with TRF2
Song, K. B., Jung, D., Jung, Y., Lee, S. G., & Lee, I. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01958-x · Cited by 182
The Fission Yeast Taz1 Protein Protects Chromosomes from Ku-Dependent End-to-End Fusions
Ferreira, M. G., & Cooper, J. P. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00154-x · Cited by 181
Ritchie, K. B., & Petes, T. D. (2000) · Genetics · doi:10.1093/genetics/155.1.475 · Cited by 173
Telomeres of polytene chromosomes in a ciliated protozoan terminate in duplex DNA loops
Murti, K. G., & Prescott, D. M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.25.14436 · Cited by 155
Exonuclease activity is required for sequence addition and Cdc13p loading at a de novo telomere
Diede, S. J., & Gottschling, D. E. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00400-6 · Cited by 149
Kim, M. M., Rivera, M. A., Botchkina, I. L., Shalaby, R., Thor, A. D., & Blackburn, E. H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.131211098 · Cited by 140
Ducray, C., Pommier, J., Martins, L., Boussin, F. D., & Sabatier, L. (1999) · Oncogene · doi:10.1038/sj.onc.1202797 · Cited by 138
Ku Binds Telomeric DNA in Vitro
Bianchi, A., & de Lange, T. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.30.21223 · Cited by 132
DNA-dependent protein kinase is not required for the p53-dependent response to DNA damage
Jimenez, G. S., Bryntesson, F., Torres‐Arzayus, M. I., Priestley, A., Beeche, M., Saito, S., Sakaguchi, K., Appella, E., Jeggo, P. A., Taccioli, G. E., et al. (1999) · Nature · doi:10.1038/21913 · Cited by 131
Human Papillomavirus E6 and E7: Proteins which deregulate the cell cycle
Tommasino, M., & Crawford, L. (1995) · BioEssays · doi:10.1002/bies.950170607 · Cited by 131
Barnes, G., & Rio, D. C. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.3.867 · Cited by 102
Guiducci, C., Cerone, M. A., & Bacchetti, S. (2001) · Oncogene · doi:10.1038/sj.onc.1204145 · Cited by 94
Rathmell, W. K., Kaufmann, W. K., Hurt, J. C., Byrd, L. L., & Chu, G. (1997) · PubMed · Cited by 82
Telomere Capping--One Strand Fits All
de Lange, T. (2001) · Science · doi:10.1126/science.1061032 · Cited by 73
Teo, S., & Jackson, S. P. (2001) · EMBO Reports · doi:10.1093/embo-reports/kve038 · Cited by 55
Cdc13 subcomplexes regulate multiple telomere functions.
Lustig, A. J. (2001) · Nature Structural Biology · doi:10.1038/86157 · Cited by 52
A New Connection at Human Telomeres: Association of the Mre11 Complex with TRF2Preprint
de Lange, T., & Petrini, J. H. J. (2000) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2000.65.265 · Cited by 29
Aline, R. F., & Stuart, K. D. (1989) · Experimental Parasitology · doi:10.1016/0014-4894(89)90008-8 · Cited by 24
Kyvig, D. E. (1976) · American Quarterly · doi:10.2307/2712541 · Cited by 17
Entrepreneurship in the community college: Revenue diversification
Brightman, R. W. (1989) · New Directions for Community Colleges · doi:10.1002/cc.36819896810 · Cited by 6
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Metadata
- Authors
- de Lange, T.
- Venue
- Oncogene
- Published
- 2002-01-21
- Volume
- 21
- Issue
- 4
- Pages
- 532-540
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W1541877559
- Cited by
- 942
- References
- 77
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 13 · 2023: 12 · 2022: 14 · 2021: 15 · 2020: 19 · 2019: 27 · 2018: 18 · 2017: 28 · 2016: 29 · 2015: 26 · 2014: 41 · 2013: 36 · 2012: 36
- FWCI
- 12.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- telomeres, telomere capping, chromosome end protection, TRF2, T-loop, DNA damage response, DNA repair, genomic instability, telomere structure, telomere length
- MeSH terms
- Ku Autoantigen, Animals, Chromosome Aberrations, DNA Helicases, DNA-Binding Proteins, Humans, Models, Genetic, Nuclear Proteins, Nucleic Acid Conformation, Recombination, Genetic, Yeasts, Telomere, Cellular Senescence, Apoptosis, Protein Serine-Threonine Kinases, Saccharomyces cerevisiae Proteins, Antigens, Nuclear, Telomeric Repeat Binding Protein 2, DNA-Activated Protein Kinase
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