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Apoptosis, Senescence, and Cancer pp 125–144Cite as

Structure and Function of the Telomere

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Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Summary

Telomeres are specialized nucleoprotein structures found at the ends of linear chromosomes that guard against aberrant chromosomal rearrangements and prevent the ends of DNA molecules from being recognized by DNA damage-sensing mechanisms. These structures were initially characterized by Hermann Muller in the 1930s and have subsequently been the subject of intense study. The essential role of the telomere in protecting chromosomes is compromised by the continuous shortening of chromosome ends that accompanies DNA replication. At least two mechanisms have been found that counteract this telomere attrition, and these mechanisms have been implicated in tumorigenesis in that they allow unchecked cellular proliferation. This chapter summarizes our current understanding of the structure and function of the mammalian telomere, its maintenance, and its role in tumor formation.

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References

  1. Muller HJ. The remaking of chromosomes. Collecting Net 1938; 8:182–95, 98.

    Google Scholar 

  2. Gall JG. Beginning of the end: origins of the telomere concept. In: Blackburn EH, Greider CW, eds. Telomeres. Cold Spring Harbor Laboratory Press. Cold Spring Horbor, NY 1995:1–10.

    Google Scholar 

  3. McClintock B. The stability of broken ends of chromosomes in Zea mays. Genetics 1941; 26: 234–82.

    PubMed  CAS  Google Scholar 

  4. Blackburn EH, Gall JG. A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena. J Mol Biol 1978; 120(1):33–53.

    Article  PubMed  CAS  Google Scholar 

  5. Oka Y, Shiota S, Nakai S, Nishida Y, Okubo S. Inverted terminal repeat sequence in the macronuclear DNA of Stylonychia pustulata. Gene 1980; 10(4):301–6.

    Article  PubMed  CAS  Google Scholar 

  6. Klobutcher LA, Swanton MT, Donini P, Prescott DM. All gene-sized DNA molecules in four species of hypotrichs have the same terminal sequence and an unusual 3′ terminus. Proc Natl Acad Sci USA 1981; 78(5):3015–9.

    Article  PubMed  CAS  Google Scholar 

  7. Szostak JW, Blackburn EH. Cloning yeast telomeres on linear plasmid vectors. Cell 1982; 29(1):245–55.

    Article  PubMed  CAS  Google Scholar 

  8. Watson JD. Origin of concatemeric T7 DNA. Nat New Biol 1972; 239(94):197–201.

    PubMed  CAS  Google Scholar 

  9. Olovnikov AM. A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. J Theor Biol 1973; 41(1):181–90.

    Article  PubMed  CAS  Google Scholar 

  10. Greider CW, Blackburn EH. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 1985; 43(2 Pt 1):405–13.

    Article  PubMed  CAS  Google Scholar 

  11. Kim NW, Piatyszek MA, Prowse KR, et al. Specific association of human telomerase activity with immortal cells and cancer. Science 1994; 266:2011–5.

    Article  PubMed  CAS  Google Scholar 

  12. Kim NW, Wu F. Advances in quantification and characterization of telomerase activity by the telomeric repeat amplification protocol (TRAP). Nucleic Acids Res 1997; 25(13):2595–7.

    Article  PubMed  CAS  Google Scholar 

  13. Lange T, Shiue L, Myers RM, et al. Structure and variability of human chromosome ends. Mol Cell Biol 1990; 10(2):518–27.

    PubMed  Google Scholar 

  14. Kipling D, Cooke HJ. Hypervariable ultra-long telomeres in mice. Nature 1990; 347(6291):400–2.

    Article  PubMed  CAS  Google Scholar 

  15. Cooke HJ, Smith BA. Variability at the telomeres of the human X/Y pseudoautosomal region. Cold Spring Harb Symp Quant Biol 1986; 51(Pt 1):213–9.

    Google Scholar 

  16. Lindsey J, McGill NI, Lindsey LA, Green DK, Cooke HJ. in vivo loss of telomeric repeats with age in humans. Mutat Res 1991; 256(1):45–8.

    PubMed  CAS  Google Scholar 

  17. Makarov VL, Hirose Y, Langmore JP. Long G tails at both ends of human chromosomes suggest a C strand degradation mechanism for telomere shortening. Cell 1997; 88(5):657–66.

    Article  PubMed  CAS  Google Scholar 

  18. McElligott R, Wellinger RJ. The terminal DNA structure of mammalian chromosomes. EMBO J 1997; 16(12):3705–14.

    Article  PubMed  CAS  Google Scholar 

  19. Wright WE, Tesmer VM, Huffman KE, Levene SD, Shay JW. Normal human chromosomes have long G-rich telomeric overhangs at one end. Genes Dev 1997; 11(21):2801–9.

    PubMed  CAS  Google Scholar 

  20. van Steensel B, Smogorzewska A, de Lange T. TRF2 protects human telomeres from end-to-end fusions. Cell 1998; 92:401–13.

    Article  PubMed  Google Scholar 

  21. Griffith JD, Comeau L, Rosenfield S, et al. Mammalian telomeres end in a large duplex loop. Cell 1999; 97(4):503–14.

    Article  PubMed  CAS  Google Scholar 

  22. Masutomi K, Yu EY, Khurts S, et al. Telomerase maintains telomere structure in normal human cells. Cell 2003; 114(2):241–53.

    Article  PubMed  CAS  Google Scholar 

  23. Hemann MT, Greider CW. G-strand overhangs on telomeres in telomerase-deficient mouse cells. Nucleic Acids Res 1999; 27(20):3964–9.

    Article  PubMed  CAS  Google Scholar 

  24. Nikitina T, Woodcock CL. Closed chromatin loops at the ends of chromosomes. J Cell Biol 2004; 166(2):161–5.

    Article  PubMed  CAS  Google Scholar 

  25. Williamson JR, Raghuraman MK, Cech TR. Monovalent cation-induced structure of telomeric DNA: the G-quartet model. Cell 1989; 59(5):871–80.

    Article  PubMed  CAS  Google Scholar 

  26. Chang CC, Kuo IC, Ling IF, et al. Detection of quadruplex DNA structures in human telomeres by a fluorescent carbazole derivative. Anal Chem 2004; 76(15):4490–4.

    Article  PubMed  CAS  Google Scholar 

  27. Choi KH, Choi BS. Formation of a hairpin structure by telomere 3′ overhang. Biochim Biophys Acta 1994; 1217(3):341–4.

    PubMed  CAS  Google Scholar 

  28. Frank-Kamenetskii M. DNA structure. The turn of the quadruplex? Nature 1989; 342(6251):737.

    Article  PubMed  CAS  Google Scholar 

  29. Shin-ya K, Wierzba K, Matsuo K, et al. Telomestatin, a novel telomerase inhibitor from Streptomyces anulatus. J Am Chem Soc 2001; 123(6):1262–3.

    Article  PubMed  CAS  Google Scholar 

  30. Kim MY, Vankayalapati H, Shin-Ya K, Wierzba K, Hurley LH. Telomestatin, a potent telomerase inhibitor that interacts quite specifically with the human telomeric intramolecular g-quadruplex. J Am Chem Soc 2002; 124(10):2098–9.

    Article  PubMed  CAS  Google Scholar 

  31. Gomez D, Paterski R, Lemarteleur T, Shin-Ya K, Mergny JL, Riou JF. Interaction of telomestatin with the telomeric single-strand overhang. J Biol Chem 2004; 279(40):41487–94.

    Article  PubMed  CAS  Google Scholar 

  32. Kim MY, Gleason-Guzman M, Izbicka E, Nishioka D, Hurley LH. The different biological effects of telomestatin and TMPyP4 can be attributed to their selectivity for interaction with intramolecular or intermolecular G-quadruplex structures. Cancer Res 2003; 63(12):3247–56.

    PubMed  CAS  Google Scholar 

  33. Dapic V, Abdomerovic V, Marrington R, et al. Biophysical and biological properties of quadruplex oligodeoxyribonucleotides. Nucleic Acids Res 2003; 31(8):2097–107.

    Article  PubMed  CAS  Google Scholar 

  34. Chong L, van Steensel B, Broccoli D, et al. A human telomeric protein. Science 1995; 270(5242):1663–7.

    Article  PubMed  CAS  Google Scholar 

  35. Broccoli D, Chong L, Oelmann S, et al. Comparison of the human and mouse genes encoding the telomeric protein, TRF1: chromosomal localization, expression and conserved protein domains. Hum Mol Genet 1997; 6(1):69–76.

    Article  PubMed  CAS  Google Scholar 

  36. Bilaud T, Brun C, Ancelin K, Koering CE, Laroche T, Gilson E. Telomeric localization of TRF2, a novel human telobox protein. Nat Genet 1997; 17(2):236–9.

    Article  PubMed  CAS  Google Scholar 

  37. Baumann P, Cech TR. Pot1, the putative telomere end-binding protein in fission yeast and humans. Science 2001; 292(5519):1171–5.

    Article  PubMed  CAS  Google Scholar 

  38. Yang Q, Zheng YL, Harris CC. POT1 and TRF2 cooperate to maintain telomeric integrity. Mol Cell Biol 2005; 25(3):1070–80.

    Article  PubMed  CAS  Google Scholar 

  39. Kim SH, Kaminker P, Campisi J. TIN2, a new regulator of telomere length in human cells. Nat Genet 1999; 23(4):405–12.

    Article  PubMed  CAS  Google Scholar 

  40. Li B, Oestreich S, de Lange T. Identification of human Rap1: implications for telomere evolution. Cell 2000; 101(5):471–83.

    Article  PubMed  CAS  Google Scholar 

  41. Ye JZ, Hockemeyer D, Krutchinsky AN, et al. POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex. Genes Dev 2004; 18(14):1649–54.

    Article  PubMed  CAS  Google Scholar 

  42. Houghtaling BR, Cuttonaro L, Chang W, Smith S. A dynamic molecular link between the telomere length regulator TRF1 and the chromosome end protector TRF2. Curr Biol 2004; 14(18):1621–31.

    Article  PubMed  CAS  Google Scholar 

  43. Liu D, Safari A, O’Connor MS, et al. PTOP interacts with POT1 and regulates its localization to telomeres. Nat Cell Biol 2004; 6(7):673–80.

    Article  PubMed  CAS  Google Scholar 

  44. de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 2005; 19(18):2100–10.

    Article  PubMed  CAS  Google Scholar 

  45. Zhou XZ, Lu KP. The Pin2/TRF1-interacting protein PinX1 is a potent telomerase inhibitor. Cell 2001; 107(3):347–59.

    Article  PubMed  CAS  Google Scholar 

  46. Smith S, Giriat I, Schmitt A, de Lange T. Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. Science 1998; 282(5393):1484–7.

    Article  PubMed  CAS  Google Scholar 

  47. Lyons RJ, Deane R, Lynch DK, et al. Identification of a novel human tankyrase through its interaction with the adaptor protein Grb14. J Biol Chem 2001; 276(20):17172–80.

    Article  PubMed  CAS  Google Scholar 

  48. Kuimov AN, Kuprash DV, Petrov VN, et al. Cloning and characterization of TNKL, a member of tankyrase gene family. Genes Immun 2001; 2(1):52–5.

    Article  PubMed  CAS  Google Scholar 

  49. Kaminker PG, Kim SH, Taylor RD, et al. TANK2, a new TRF1-associated poly(ADP-ribose) polymerase, causes rapid induction of cell death upon overexpression. J Biol Chem 2001; 276(38):35891–9.

    Article  PubMed  CAS  Google Scholar 

  50. Bailey SM, Meyne J, Chen DJ, et al. DNA double-strand break repair proteins are required to cap the ends of mammalian chromosomes. Proc Natl Acad Sci USA 1999; 96(26):14899–904.

    Article  PubMed  CAS  Google Scholar 

  51. Cary RB, Peterson SR, Wang J, Bear DG, Bradbury EM, Chen DJ. DNA looping by Ku and the DNA-dependent protein kinase. Proc Natl Acad Sci USA 1997; 94(9):4267–72.

    Article  PubMed  CAS  Google Scholar 

  52. Zhu XD, Kuster B, Mann M, Petrini JH, de Lange T. Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres. Nat Genet 2000; 25(3):347–52.

    Article  PubMed  CAS  Google Scholar 

  53. Lillard-Wetherell K, Machwe A, Langland GT, et al. Association and regulation of the BLM helicase by the telomere proteins TRF1 and TRF2. Hum Mol Genet 2004; 13(17):1919–32.

    Article  PubMed  CAS  Google Scholar 

  54. Du X, Shen J, Kugan N, et al. Telomere shortening exposes functions for the mouse Werner and Bloom syndrome genes. Mol Cell Biol 2004; 24(19):8437–46.

    Article  PubMed  CAS  Google Scholar 

  55. Crabbe L, Verdun RE, Haggblom CI, Karlseder J. Defective telomere lagging strand synthesis in cells lacking WRN helicase activity. Science 2004; 306(5703):1951–3.

    Article  PubMed  CAS  Google Scholar 

  56. Opresko PL, von Kobbe C, Laine JP, Harrigan J, Hickson ID, Bohr VA. Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases. J Biol Chem 2002; 277(43):41110–9.

    Article  PubMed  CAS  Google Scholar 

  57. Takai H, Smogorzewska A, de Lange T. DNA damage foci at dysfunctional telomeres. Curr Biol 2003; 13(17):1549–56.

    Article  PubMed  CAS  Google Scholar 

  58. d’Adda di Fagagna F, Reaper PM, Clay-Farrace L, et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature 2003; 426(6963):194–8.

    Article  PubMed  CAS  Google Scholar 

  59. Iijima K, Komatsu K, Matsuura S, Tauchi H. The Nijmegen breakage syndrome gene and its role in genome stability. Chromosoma 2004; 113(2):53–61.

    Article  PubMed  CAS  Google Scholar 

  60. van Steensel B, de Lange T. Control of telomere length by the human telomeric protein TRF1. Nature 1997; 385(6618):740–3.

    Article  PubMed  Google Scholar 

  61. Liu D, O’Connor MS, Qin J, Songyang Z. Telosome, a mammalian telomere-associated complex formed by multiple telomeric proteins. J Biol Chem 2004; 279(49):51338–42.

    Article  PubMed  CAS  Google Scholar 

  62. Ye JZ, Donigian JR, van Overbeek M, et al. TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2 complex on telomeres. J Biol Chem 2004; 279(45):47264–71.

    Article  PubMed  CAS  Google Scholar 

  63. Blackburn EH. Telomere states and cell fates. Nature 2000; 408(6808):53–6.

    Article  PubMed  CAS  Google Scholar 

  64. Karlseder J, Smogorzewska A, de Lange T. Senescence induced by altered telomere state, not telomere loss. Science 2002; 295(5564):2446–9.

    Article  PubMed  CAS  Google Scholar 

  65. Beattie TL, Zhou W, Robinson MO, Harrington L. Functional multimerization of the human telomerase reverse transcriptase. Mol Cell Biol 2001; 21(18):6151–60.

    Article  PubMed  CAS  Google Scholar 

  66. Holt SE, Aisner DL, Baur J, et al. Functional requirement of p23 and Hsp90 in telomerase complexes. Genes Dev 1999; 13(7):817–26.

    PubMed  CAS  Google Scholar 

  67. Forsythe HL, Jarvis JL, Turner JW, Elmore LW, Holt SE. Stable association of hsp90 and p23, but not hsp70, with active human telomerase. J Biol Chem 2001; 276(19):15571–4.

    Article  PubMed  CAS  Google Scholar 

  68. Masutomi K, Kaneko S, Hayashi N, et al. Telomerase activity reconstituted in vitro with purified human telomerase reverse transcriptase and human telomerase RNA component. J Biol Chem 2000; 275(29):22568–73.

    Article  PubMed  CAS  Google Scholar 

  69. Chang JT, Chen YL, Yang HT, Chen CY, Cheng AJ. Differential regulation of telomerase activity by six telomerase subunits. Eur J Biochem 2002; 269(14):3442–50.

    Article  PubMed  CAS  Google Scholar 

  70. Mitchell JR, Wood E, Collins K. A telomerase component is defective in the human disease dyskeratosis congenita. Nature 1999; 402(6761):551–5.

    Article  PubMed  CAS  Google Scholar 

  71. Ruggero D, Grisendi S, Piazza F, et al. Dyskeratosis congenita and cancer in mice deficient in ribosomal RNA modification. Science 2003; 299(5604):259–62.

    Article  PubMed  CAS  Google Scholar 

  72. Heiss NS, Knight SW, Vulliamy TJ, et al. X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions. Nat Genet 1998; 19(1):32–8.

    Article  PubMed  CAS  Google Scholar 

  73. Avilion AA, Piatyszek MA, Gupta J, Shay JW, Bacchetti S, Greider CW. Human telomerase RNA and telomerase activity in immortal cell lines and tumor tissues. Cancer Res 1996; 56(3):645–50.

    PubMed  CAS  Google Scholar 

  74. Shay JW, Bacchetti S. A survey of telomerase activity in human cancer. Eur J Cancer 1997; 33(5):787–91.

    Article  PubMed  CAS  Google Scholar 

  75. Broccoli D, Young JW, de Lange T. Telomerase activity in normal and malignant hematopoietic cells. Proc Natl Acad Sci USA 1995; 92(20):9082–6.

    Article  PubMed  CAS  Google Scholar 

  76. Colgin LM, Wilkinson C, Englezou A, Kilian A, Robinson MO, Reddel RR. The hTERTalpha splice variant is a dominant negative inhibitor of telomerase activity. Neoplasia 2000; 2(5):426–32.

    Article  PubMed  CAS  Google Scholar 

  77. Yi X, White DM, Aisner DL, Baur JA, Wright WE, Shay JW. An alternate splicing variant of the human telomerase catalytic subunit inhibits telomerase activity. Neoplasia 2000; 2(5):433–40.

    Article  PubMed  CAS  Google Scholar 

  78. Lundblad V, Blackburn EH. An alternative pathway for yeast telomere maintenance rescues est1- senescence. Cell 1993; 73:347–60.

    Article  PubMed  CAS  Google Scholar 

  79. Snow BE, Erdmann N, Cruickshank J, et al. Functional conservation of the telomerase protein Est1p in humans. Curr Biol 2003; 13(8):698–704.

    Article  PubMed  CAS  Google Scholar 

  80. Reichenbach P, Hoss M, Azzalin CM, Nabholz M, Bucher P, Lingner J. A human homolog of yeast Est1 associates with telomerase and uncaps chromosome ends when overexpressed. Curr Biol 2003; 13(7):568–74.

    Article  PubMed  CAS  Google Scholar 

  81. Kang SS, Kwon T, Kwon DY, Do SI. Akt protein kinase enhances human telomerase activity through phosphorylation of telomerase reverse transcriptase subunit. J Biol Chem 1999; 274(19):13085–90.

    Article  PubMed  CAS  Google Scholar 

  82. Wong JM, Kusdra L, Collins K. Subnuclear shuttling of human telomerase induced by transformation and DNA damage. Nat Cell Biol 2002; 4(9):731–6.

    Article  PubMed  CAS  Google Scholar 

  83. Yang Y, Chen Y, Zhang C, Huang H, Weissman SM. Nucleolar localization of hTERT protein is associated with telomerase function. Exp Cell Res 2002; 277(2):201–9.

    Article  PubMed  CAS  Google Scholar 

  84. Bryan TM, Englezou A, Gupta J, Bacchetti S, Reddel RR. Telomere elongation in immortal human cells without detectable telomerase activity. EMBO J 1995; 14:4240–8.

    PubMed  CAS  Google Scholar 

  85. Bryan TM, Englezou A, Dalla-Pozza L, Dunham MA, Reddel RR. Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nat Med 1997; 3:1271–4.

    Article  PubMed  CAS  Google Scholar 

  86. Marciniak RA, Cavazos D, Montellano R, Chen Q, Guarente L, Johnson FB. A novel telomere structure in human ALT cell line. Cancer Res 2005; 65:2730–7.

    Article  PubMed  CAS  Google Scholar 

  87. Fasching CL, Bower K, Reddel RR. Telomerase-independent telomere length maintenance in the absence of ALT-associated PML bodies. Cancer Res 2005; 65:2722–9.

    Article  PubMed  CAS  Google Scholar 

  88. Ogino H, Nakabayashi K, Suzuki M, et al. Release of telomeric DNA from chromosomes in immortal human cells lacking telomerase activity. Biochem Biophys Res Commun 1998; 248:223–7.

    Article  PubMed  CAS  Google Scholar 

  89. Cesare AJ, Griffith JD. Telomeric DNA in ALT cells is characterized by free telomeric circles and heterogeneous t-loops. Mol Cell Biol 2004; 24(22):9948–57.

    Article  PubMed  CAS  Google Scholar 

  90. Natarajan S, McEachern MJ. Recombinational telomere elongation promoted by DNA circles. Mol Cell Biol 2002; 22(13):4512–21.

    Article  PubMed  CAS  Google Scholar 

  91. Yeager T, Neumann A, Englezou A, Huschtscha L, Noble J, Reddel R. Telomerase-negative immortalized human cells contain a novel type of promyelocytic leukemia (PML) body. Cancer Res 1999; 59:4175–9.

    PubMed  CAS  Google Scholar 

  92. Bernardi R, Pandolfi PP. Role of PML and the PML-nuclear body in the control of programmed cell death. Oncogene 2003; 22(56):9048–57.

    Article  PubMed  CAS  Google Scholar 

  93. Salomoni P, Pandolfi PP. The role of PML in tumor suppression. Cell 2002; 108(2):165–70.

    Article  PubMed  CAS  Google Scholar 

  94. Grobelny JV, Godwin AK, Broccoli D. ALT-associated PML bodies are present in viable cells and are enriched in cells in the G2/M phase of the cell cycle. J Cell Sci 2000; 113:4577–85.

    PubMed  CAS  Google Scholar 

  95. Wu G, Lee WH, Chen PL. NBS1 and TRF1 colocalize at promyelocytic leukemia bodies during late S/G2 phases in immortalized telomerase-negative cells. Implication of NBS1 in alternative lengthening of telomeres. J Biol Chem 2000; 275(39):30618–22.

    Article  PubMed  CAS  Google Scholar 

  96. Montgomery E, Argani P, Hicks JL, DeMarzo AM, Meeker AK. Telomere lengths of translocation-associated and nontranslocation-associated sarcomas differ dramatically. Am J Pathol 2004; 164(5):1523–9.

    PubMed  CAS  Google Scholar 

  97. Teng SC, Zakian VA. Telomere-telomere recombination is an efficient bypass pathway for telomere maintenance in Saccharomyces cerevisiae. Mol Cell Biol 1999; 19(12):8083–93.

    PubMed  CAS  Google Scholar 

  98. Teng SC, Chang J, McCowan B, Zakian VA. Telomerase-independent lengthening of yeast telomeres occurs by an abrupt Rad50p-dependent, Rif-inhibited recombinational process. Mol Cell 2000; 6(4):947–52.

    Article  PubMed  CAS  Google Scholar 

  99. Murnane JP, Sabatier L, Marder BA, Morgan WF. Telomere dynamics in an immortal human cell line. EMBO J 1994; 13(20):4953–62.

    PubMed  CAS  Google Scholar 

  100. Dunham MA, Neymann AA, Fasching CL, Reddel RR. Telomere maintenance by recombination in human cells. Nat Genet 2000; 26:447–50.

    Article  PubMed  CAS  Google Scholar 

  101. Niida H, Shinkai Y, Hande MP, et al. Telomere maintenance in telomerase-deficient mouse embryonic stem cells: characterization of an amplified telomeric DNA. Mol Cell Biol 2000; 20(11):4114–27.

    Article  Google Scholar 

  102. Bechter OE, Zou Y, Walker W, Wright WE, Shay JW. Telomeric recombination in mismatch repair deficient human colon cancer cells after telomerase inhibition. Cancer Res 2004; 64(10):3444–51.

    Article  PubMed  CAS  Google Scholar 

  103. Londono-Vallejo JA, Der-Sarkissian H, Cazes L, Bacchetti S, Reddel RR. Alternative lengthening of telomeres is characterized by high rates of telomeric exchange. Cancer Res 2004; 64(7):2324–7.

    Article  PubMed  CAS  Google Scholar 

  104. Bailey SM, Brenneman MA, Goodwin EH. Frequent recombination in telomeric DNA may extend the proliferative life of telomerase-negative cells. Nucleic Acids Res 2004; 32(12):3743–51.

    Article  PubMed  CAS  Google Scholar 

  105. Karlseder J, Broccoli D, Dai Y, Hardy S, de Lange T. p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science 1999; 283(5406):1321–5.

    Article  PubMed  CAS  Google Scholar 

  106. Chin L, Artandi SE, Shen Q, et al. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell 1999; 97(4):527–38.

    Article  PubMed  CAS  Google Scholar 

  107. Lee HW, Blasco MA, Gottlieb GJ, Horner JW, 2nd, Greider CW, DePinho RA. Essential role of mouse telomerase in highly proliferative organs. Nature 1998; 392(6676):569–74.

    Article  PubMed  CAS  Google Scholar 

  108. de Lange T. Activation of telomerase in a human tumor. Proc Natl Acad Sci USA 1994; 91(8): 2882–5.

    Article  PubMed  Google Scholar 

  109. Elmore LW, Turner KC, Gollahon LS, Landon MR, Jackson-Cook CK, Holt SE. Telomerase protects cancer-prone human cells from chromosomal instability and spontaneous immortalization. Cancer Biol Ther 2002; 1(4):391–7.

    PubMed  CAS  Google Scholar 

  110. Chin K, de Solorzano CO, Knowles D, et al. In situ analyses of genome instability in breast cancer. Nat Genet 2004; 36(9):984–8.

    Article  PubMed  CAS  Google Scholar 

  111. Banik SS, Counter CM. Characterization of interactions between PinX1 and human telomerase subunits hTERT and hTR. J Biol Chem 2004; 279(50):51745–8.

    Article  PubMed  CAS  Google Scholar 

  112. Counter CM, Meyerson M, Eaton EN, et al. Telomerase activity is restored in human cells by ectopic expression of hTERT (hEST2), the catalytic subunit of telomerase. Oncogene 1998; 16(9):1217–22.

    Article  PubMed  CAS  Google Scholar 

  113. Orren DK, Theodore S, Machwe A. The Werner syndrome helicase/exonuclease (WRN) disrupts and degrades D-loops in vitro. Biochemistry 2002; 41(46):13483–8.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Jay E. Johnson PhD
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  2. Dominique Broccoli PhD
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Editors and Affiliations

  1. Department of Pharmacology and Toxicology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA

    David A. Gewirtz

  2. Departments of Medicine, Pharmacology and Toxicology, Biochemistry and Massey Cancer Center, Virginia Commonwealth, Richmond, VA

    Shawn E. Holt

  3. Departments of Pathology, Human Genetics, Pharmacology and Toxicology, Biochemistry and Massey Cancer Center, Virginia Commonwealth, Richmond, VA

    Steven Grant

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Johnson, J.E., Broccoli, D. (2007). Structure and Function of the Telomere. In: Gewirtz, D.A., Holt, S.E., Grant, S. (eds) Apoptosis, Senescence, and Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-221-2_7

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