1932

Abstract

Telomeres are specialized chromatin structures that protect chromosome ends from dangerous processing events. In most tissues, telomeres shorten with each round of cell division, placing a finite limit on cell growth. In rapidly dividing cells, including the majority of human cancers, cells bypass this growth limit through telomerase-catalyzed maintenance of telomere length. The dynamic properties of telomeres and telomerase render them difficult to study using ensemble biochemical and structural techniques. This review describes single-molecule approaches to studying how individual components of telomeres and telomerase contribute to function. Single-molecule methods provide a window into the complex nature of telomeres and telomerase by permitting researchers to directly visualize and manipulate the individual protein, DNA, and RNA molecules required for telomere function. The work reviewed in this article highlights how single-molecule techniques have been utilized to investigate the function of telomeres and telomerase.

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2017-05-22
2024-03-29
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Literature Cited

  1. Akiyama BM, Parks JW, Stone MD. 1.  2015. The telomerase essential N-terminal domain promotes DNA synthesis by stabilizing short RNA–DNA hybrids. Nucleic Acids Res 43:5537–49 [Google Scholar]
  2. Alves D, Li H, Codrington R, Orte A, Ren X. 2.  et al. 2008. Single-molecule analysis of human telomerase monomer. Nat. Chem. Biol. 4:287–89 [Google Scholar]
  3. Amiard S, Doudeau M, Pinte S, Poulet A, Lenain C. 3.  et al. 2007. A topological mechanism for TRF2-enhanced strand invasion. Nat. Struct. Mol. Biol. 14:147–54 [Google Scholar]
  4. An N, Fleming AM, Burrows CJ. 4.  2013. Interactions of the human telomere sequence with the nanocavity of the α-hemolysin ion channel reveal structure-dependent electrical signatures for hybrid folds. J. Am. Chem. Soc. 135:8562–70 [Google Scholar]
  5. An N, Fleming AM, Middleton EG, Burrows CJ. 5.  2014. Single-molecule investigation of G-quadruplex folds of the human telomere sequence in a protein nanocavity. PNAS 111:14325–31 [Google Scholar]
  6. An N, Fleming AM, White HS, Burrows CJ. 6.  2015. Nanopore detection of 8-oxoguanine in the human telomere repeat sequence. ACS Nano 9:4296–307 [Google Scholar]
  7. Bandaria JN, Qin P, Berk V, Chu S, Yildiz A. 7.  2016. Shelterin protects chromosome ends by compacting telomeric chromatin. Cell 164:735–46 [Google Scholar]
  8. Beattie TL, Zhou W, Robinson MO, Harrington L. 8.  2001. Functional multimerization of the human telomerase reverse transcriptase. Mol. Cell. Biol. 21:6151–60 [Google Scholar]
  9. Benarroch-Popivker D, Pisano S, Mendez-Bermudez A, Lototska L, Kaur P. 9.  et al. 2016. TRF2-mediated control of telomere DNA topology as a mechanism for chromosome-end protection. Mol. Cell 61:274–86 [Google Scholar]
  10. Berman AJ, Akiyama BM, Stone MD, Cech TR. 10.  2011. The RNA accordion model for template positioning by telomerase RNA during telomeric DNA synthesis. Nat. Struct. Mol. Biol. 18:1371–75 [Google Scholar]
  11. Bryan TM, Goodrich KJ, Cech TR. 11.  2000. Telomerase RNA bound by protein motifs specific to telomerase reverse transcriptase. Mol. Cell 6:493–99 [Google Scholar]
  12. Cash DD, Cohen-Zontag O, Kim N-K, Shefer K, Brown Y. 12.  et al. 2013. Pyrimidine motif triple helix in the Kluyveromyces lactis telomerase RNA pseudoknot is essential for function in vivo. PNAS 110:10970–75 [Google Scholar]
  13. Cash DD, Feigon J. 13.  2017. Structure and folding of the Tetrahymena telomerase RNA pseudoknot. Nucleic Acids Res 45:482–95 [Google Scholar]
  14. Cech TR. 14.  2004. Beginning to understand the end of the chromosome. Cell 116:273–79 [Google Scholar]
  15. Chan H, Wang Y, Feigon J. 14a.  2017. Progress in human and Tetrahymena telomerase structure determination. Annu. Rev. Biophys. 46:199–225 [Google Scholar]
  16. Chen G, Wen J-D, Tinoco I Jr.. 15.  2007. Single-molecule mechanical unfolding and folding of a pseudoknot in human telomerase RNA. RNA 13:2175–88 [Google Scholar]
  17. Chen JL, Greider CW. 16  2005. Functional analysis of the pseudoknot structure in human telomerase RNA. PNAS 102:8080–85 [Google Scholar]
  18. Chen L-Y, Redon S, Lingner J. 17.  2012. The human CST complex is a terminator of telomerase activity. Nature 488:540–44 [Google Scholar]
  19. Chu J-F, Chang T-C, Li H-W. 18.  2010. Single-molecule TPM studies on the conversion of human telomeric DNA. Biophys. J. 98:1608–16 [Google Scholar]
  20. Cole DI, Legassie JD, Bonifacio LN, Sekaran VG, Ding F. 19.  et al. 2012. New models of Tetrahymena telomerase RNA from experimentally derived constraints and modeling. J. Am. Chem. Soc. 134:20070–80 [Google Scholar]
  21. Comolli LR, Smirnov I, Xu L, Blackburn EH, James TL. 20.  2002. A molecular switch underlies a human telomerase disease. PNAS 99:16998–7003 [Google Scholar]
  22. Croteau DL, Popuri V, Opresko PL, Bohr VA. 21.  2014. Human RecQ helicases in DNA repair, recombination, and replication. Annu. Rev. Biochem. 83:519–52 [Google Scholar]
  23. Cusanelli E, Chartrand P. 22.  2015. Telomeric repeat-containing RNA TERRA: a noncoding RNA connecting telomere biology to genome integrity. Front. Genet. 6:143 [Google Scholar]
  24. Dai J, Carver M, Yang D. 23.  2008. Polymorphism of human telomeric quadruplex structures. Biochimie 90:1172–83 [Google Scholar]
  25. de Lange T. 24.  2005. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 19:2100–10 [Google Scholar]
  26. Deniz AA, Mukhopadhyay S, Lemke EA. 25.  2008. Single-molecule biophysics: at the interface of biology, physics and chemistry. J. R. Soc. Interface 5:15–45 [Google Scholar]
  27. Dhakal S, Cui Y, Koirala D, Ghimire C, Kushwaha S. 26.  et al. 2013. Structural and mechanical properties of individual human telomeric G-quadruplexes in molecularly crowded solutions. Nucleic Acids Res 41:3915–23 [Google Scholar]
  28. Dhakal S, Schonhoft JD, Koirala D, Yu Z, Basu S, Mao H. 27.  2010. Coexistence of an ILPR i-motif and a partially folded structure with comparable mechanical stability revealed at the single-molecule level. J. Am. Chem. Soc. 132:8991–97 [Google Scholar]
  29. Doksani Y, Wu JY, de Lange T, Zhuang X. 28.  2013. Super-resolution fluorescence imaging of telomeres reveals TRF2-dependent T-loop formation. Cell 155:345–56 [Google Scholar]
  30. Drosopoulos WC, Kosiyatrakul ST, Schildkraut CL. 29.  2015. BLM helicase facilitates telomere replication during leading strand synthesis of telomeres. J. Cell Biol. 210:191–208 [Google Scholar]
  31. Eckert B, Collins K. 30.  2012. Roles of telomerase reverse transcriptase N-terminal domain in assembly and activity of Tetrahymena telomerase holoenzyme. J. Biol. Chem. 287:12805–14 [Google Scholar]
  32. Erdel F, Kratz K, Willcox S, Griffith JD, Greene EC, de Lange T. 31.  2017. Telomere recognition and assembly mechanism of mammalian shelterin. Cell. Rep. 18:41–53 [Google Scholar]
  33. Feng J, Funk WD, Wang SS, Weinrich SL, Avilion AA. 32.  et al. 1995. The RNA component of human telomerase. Science 269:1236–41 [Google Scholar]
  34. Fouquerel E, Lormand J, Bose A, Lee H-T, Kim GS. 33.  et al. 2016. Oxidative guanine base damage regulates human telomerase activity. Nat. Struct. Mol. Biol. 23:1092–100 [Google Scholar]
  35. Funayama R, Nakahara Y, Kado S, Tanaka M, Kimura K. 34.  2014. A single-molecule force-spectroscopic study on stabilization of G-quadruplex DNA by a telomerase inhibitor. Analyst 139:4037–43 [Google Scholar]
  36. Galati A, Micheli E, Cacchione S. 35.  2013. Chromatin structure in telomere dynamics. Front. Oncol. 3:46 [Google Scholar]
  37. Greenleaf WJ, Woodside MT, Block SM. 36.  2007. High-resolution, single-molecule measurements of biomolecular motion. Annu. Rev. Biophys. Biomol. Struct. 36:171–90 [Google Scholar]
  38. Greider CW. 37.  1991. Telomerase is processive. Mol. Cell. Biol. 11:4572–80 [Google Scholar]
  39. Greider CW, Blackburn EH. 38.  1985. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43:405–13 [Google Scholar]
  40. Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A. 39.  et al. 1999. Mammalian telomeres end in a large duplex loop. Cell 97:503–14 [Google Scholar]
  41. Hayflick L. 40.  1965. The limited in vitro lifetime of human diploid cell strains. Exp. Cell Res. 37:614–36 [Google Scholar]
  42. Hayflick L. 41.  1985. The cell biology of aging. Clin. Geriatr. Med. 1:15–27 [Google Scholar]
  43. Hengesbach M, Kim N-K, Feigon J, Stone MD. 42.  2012. Single-molecule FRET reveals the folding dynamics of the human telomerase RNA pseudoknot domain. Angew. Chem. Int. Ed. Engl. 51:5876–79 [Google Scholar]
  44. Hockemeyer D, Collins K. 43.  2015. Control of telomerase action at human telomeres. Nat. Struct. Mol. Biol. 22:848–52 [Google Scholar]
  45. Huang B, Babcock H, Zhuang X. 44.  2010. Breaking the diffraction barrier: super-resolution imaging of cells. Cell 143:1047–58 [Google Scholar]
  46. Hwang H, Buncher N, Opresko PL, Myong S. 45.  2012. POT1-TPP1 regulates telomeric overhang structural dynamics. Structure 20:1872–80 [Google Scholar]
  47. Hwang H, Kreig A, Calvert J, Lormand J, Kwon Y. 46.  et al. 2014. Telomeric overhang length determines structural dynamics and accessibility to telomerase and ALT-associated proteins. Structure 22:842–53 [Google Scholar]
  48. Hwang H, Opresko P, Myong S. 47.  2014. Single-molecule real-time detection of telomerase extension activity. Sci. Rep. 4:6391 [Google Scholar]
  49. Jena PV, Shirude PS, Okumus B, Laxmi-Reddy K, Godde F. 48.  et al. 2009. G-quadruplex DNA bound by a synthetic ligand is highly dynamic. J. Am. Chem. Soc. 131:12522–23 [Google Scholar]
  50. Jiang J, Chan H, Cash DD, Miracco EJ, Ogorzalek Loo RR. 49.  et al. 2015. Structure of Tetrahymena telomerase reveals previously unknown subunits, functions, and interactions. Science 350:aab4070 [Google Scholar]
  51. Jurczyluk J, Nouwens AS, Holien JK, Adams TE, Lovrecz GO. 50.  et al. 2011. Direct involvement of the TEN domain at the active site of human telomerase. Nucleic Acids Res 39:1774–88 [Google Scholar]
  52. Kaur P, Wu D, Lin J, Countryman P, Bradford KC. 51.  et al. 2016. Enhanced electrostatic force microscopy reveals higher-order DNA looping mediated by the telomeric protein TRF2. Sci. Rep. 6:20513 [Google Scholar]
  53. Kim N-K, Zhang Q, Zhou J, Theimer CA, Peterson RD, Feigon J. 52.  2008. Solution structure and dynamics of the wild-type pseudoknot of human telomerase RNA. J. Mol. Biol. 384:1249–61 [Google Scholar]
  54. Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD. 53.  et al. 1994. Specific association of human telomerase activity with immortal cells and cancer. Science 266:2011–15 [Google Scholar]
  55. Koirala D, Dhakal S, Ashbridge B, Sannohe Y, Rodriguez R. 54.  et al. 2011. A single-molecule platform for investigation of interactions between G-quadruplexes and small-molecule ligands. Nat. Chem. 3:782–87 [Google Scholar]
  56. Lai CK, Miller MC, Collins K. 55.  2002. Template boundary definition in Tetrahymena telomerase. Genes Dev 16:415–20 [Google Scholar]
  57. Lai CK, Miller MC, Collins K. 56.  2003. Roles for RNA in telomerase nucleotide and repeat addition processivity. Mol. Cell 11:1673–83 [Google Scholar]
  58. Lee JY, Kim DS. 57.  2009. Dramatic effect of single-base mutation on the conformational dynamics of human telomeric G-quadruplex. Nucleic Acids Res 37:3625–34 [Google Scholar]
  59. Lee JY, Okumus B, Kim DS, Ha T. 58.  2005. Extreme conformational diversity in human telomeric DNA. PNAS 102:18938–43 [Google Scholar]
  60. Lee JY, Yoon J, Kihm HW, Kim DS. 59.  2008. Structural diversity and extreme stability of unimolecular Oxytricha nova telomeric G-quadruplex. Biochemistry 47:3389–96 [Google Scholar]
  61. Lin J, Countryman P, Buncher N, Kaur P, E L. 60.  et al. 2014. TRF1 and TRF2 use different mechanisms to find telomeric DNA but share a novel mechanism to search for protein partners at telomeres. Nucleic Acids Res 42:2493–504 [Google Scholar]
  62. Lin J, Countryman P, Chen H, Pan H, Fan Y. 61.  et al. 2016. Functional interplay between SA1 and TRF1 in telomeric DNA binding and DNA–DNA pairing. Nucleic Acids Res 44:6363–76 [Google Scholar]
  63. Liu S-W, Chu J-F, Tsai C-T, Fang H-C, Chang T-C, Li H-W. 62.  2013. Assaying the binding strength of G-quadruplex ligands using single-molecule TPM experiments. Anal. Biochem. 436:101–8 [Google Scholar]
  64. Long X, Parks JW, Bagshaw CR, Stone MD. 63.  2013. Mechanical unfolding of human telomere G-quadruplex DNA probed by integrated fluorescence and magnetic tweezers spectroscopy. Nucleic Acids Res 41:2746–55 [Google Scholar]
  65. Long X, Stone MD. 64.  2013. Kinetic partitioning modulates human telomere DNA G-quadruplex structural polymorphism. PLOS ONE 8:e83420 [Google Scholar]
  66. Lue NF, Zhou R, Chico L, Mao N, Steinberg-Neifach O, Ha T. 65.  2013. The telomere capping complex CST has an unusual stoichiometry, makes multipartite interaction with G-tails, and unfolds higher-order G-tail structures. PLOS Genet 9:e1003145 [Google Scholar]
  67. Lynch S, Baker H, Byker SG, Zhou D, Sinniah K. 66.  2009. Single molecule force spectroscopy on G-quadruplex DNA. Chemistry 15:8113–16 [Google Scholar]
  68. Mason M, Schuller A, Skordalakes E. 67.  2011. Telomerase structure function. Curr. Opin. Struct. Biol. 21:92–100 [Google Scholar]
  69. McClintock B. 68.  1941. The stability of broken ends of chromosomes in Zea mays. Genetics 26:234–82 [Google Scholar]
  70. Mihalusova M, Wu JY, Zhuang X. 69.  2011. Functional importance of telomerase pseudoknot revealed by single-molecule analysis. PNAS 108:20339–44 [Google Scholar]
  71. Miracco EJ, Jiang J, Cash DD, Feigon J. 70.  2014. Progress in structural studies of telomerase. Curr. Opin. Struct. Biol. 24:115–24 [Google Scholar]
  72. Miyake Y, Nakamura M, Nabetani A, Shimamura S, Tamura M. 71.  et al. 2009. RPA-like mammalian Ctc1-Stn1-Ten1 complex binds to single-stranded DNA and protects telomeres independently of the Pot1 pathway. Mol. Cell 36:193–206 [Google Scholar]
  73. Moffitt JR, Chemla YR, Smith SB, Bustamante C. 72.  2008. Recent advances in optical tweezers. Annu. Rev. Biochem. 77:205–28 [Google Scholar]
  74. Muller HJ. 73.  1938. The remaking of chromosomes. Collect. Net 13:182–98 [Google Scholar]
  75. Müller S, Laxmi-Reddy K, Jena PV, Baptiste B, Dong Z. 74.  et al. 2014. Targeting DNA G-quadruplexes with helical small molecules. ChemBioChem 15:2563–70 [Google Scholar]
  76. Nakamura TM, Morin GB, Chapman KB, Weinrich SL, Andrews WH. 75.  et al. 1997. Telomerase catalytic subunit homologs from fission yeast and human. Science 277:955–59 [Google Scholar]
  77. Neuman KC, Nagy A. 76.  2008. Single-molecule force spectroscopy: optical tweezers, magnetic tweezers and atomic force microscopy. Nat. Methods 5:491–505 [Google Scholar]
  78. Noer SL, Preus S, Gudnason D, Aznauryan M, Mergny J-L, Birkedal V. 77.  2016. Folding dynamics and conformational heterogeneity of human telomeric G-quadruplex structures in Na+ solutions by single molecule FRET microscopy. Nucleic Acids Res 44:464–71 [Google Scholar]
  79. O'Donnell M, Li H. 78.  2016. The eukaryotic replisome goes under the microscope. Curr. Biol. 26:R247–56 [Google Scholar]
  80. Oganesian L, Bryan TM. 79.  2007. Physiological relevance of telomeric G-quadruplex formation: a potential drug target. BioEssays 29:155–65 [Google Scholar]
  81. Okamoto K, Sannohe Y, Mashimo T, Sugiyama H, Terazima M. 80.  2008. G-quadruplex structures of human telomere DNA examined by single molecule FRET and BrG-substitution. Bioorg. Med. Chem 16:6873–79 [Google Scholar]
  82. Okumus B, Ha T. 81.  2010. Real-time observation of G-quadruplex dynamics using single-molecule FRET microscopy. Methods Mol. Biol. 608:81–96 [Google Scholar]
  83. Olovnikov AM. 82.  1973. A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. J. Theor. Biol. 41:181–90 [Google Scholar]
  84. Parks JW, Kappel K, Das R, Stone MD. 83.  2017. Single molecule FRET-Rosetta reveals RNA structural rearrangements during human telomerase catalysis. RNA 23:175–188 [Google Scholar]
  85. Parks JW, Stone MD. 84.  2014. Coordinated DNA dynamics during the human telomerase catalytic cycle. Nat. Commun. 5:4146 [Google Scholar]
  86. Qureshi MH, Ray S, Sewell AL, Basu S, Balci H. 85.  2012. Replication protein A unfolds G-quadruplex structures with varying degrees of efficiency. J. Phys. Chem. B 116:5588–94 [Google Scholar]
  87. Ray S, Bandaria JN, Qureshi MH, Yildiz A, Balci H. 86.  2014. G-quadruplex formation in telomeres enhances POT1/TPP1 protection against RPA binding. PNAS 111:2990–95 [Google Scholar]
  88. Ray S, Qureshi MH, Malcolm DW, Budhathoki JB, Celik U, Balci H. 87.  2013. RPA-mediated unfolding of systematically varying G-quadruplex structures. Biophys. J. 104:2235–45 [Google Scholar]
  89. Ren X, Li H, Clarke RW, Alves DA, Ying L. 88.  et al. 2006. Analysis of human telomerase activity and function by two color single molecule coincidence fluorescence spectroscopy. J. Am. Chem. Soc. 128:4992–5000 [Google Scholar]
  90. Rezler EM, Bearss DJ, Hurley LH. 89.  2002. Telomeres and telomerases as drug targets. Curr. Opin. Pharmacol. 2:415–23 [Google Scholar]
  91. Rhodes D, Lipps HJ. 90.  2015. G-quadruplexes and their regulatory roles in biology. Nucleic Acids Res 43:8627–37 [Google Scholar]
  92. Robart AR, Collins K. 91.  2011. Human telomerase domain interactions capture DNA for TEN domain-dependent processive elongation. Mol. Cell 42:308–18 [Google Scholar]
  93. Roy R, Hohng S, Ha T. 92.  2008. A practical guide to single-molecule FRET. Nat. Methods 5:507–16 [Google Scholar]
  94. Roy R, Kozlov AG, Lohman TM, Ha T. 93.  2009. SSB protein diffusion on single-stranded DNA stimulates RecA filament formation. Nature 461:1092–97 [Google Scholar]
  95. Sauerwald A, Sandin S, Cristofari G, Scheres SH, Lingner J, Rhodes D. 94.  2013. Structure of active dimeric human telomerase. Nat. Struct. Mol. Biol. 20:454–60 [Google Scholar]
  96. Schmidt JC, Cech TR. 95.  2015. Human telomerase: biogenesis, trafficking, recruitment, and activation. Genes Dev 29:1095–105 [Google Scholar]
  97. Schmidt JC, Zaug AJ, Cech TR. 96.  2016. Live cell imaging reveals the dynamics of telomerase recruitment to telomeres. Cell 166:1188–97 [Google Scholar]
  98. Selvam S, Koirala D, Yu Z, Mao H. 97.  2014. Quantification of topological coupling between DNA superhelicity and G-quadruplex formation. J. Am. Chem. Soc. 136:13967–70 [Google Scholar]
  99. Selvam S, Yu Z, Mao H. 98.  2016. Exploded view of higher order G-quadruplex structures through click-chemistry assisted single-molecule mechanical unfolding. Nucleic Acids Res 44:45–55 [Google Scholar]
  100. Selvin PR, Ha T. 99.  2008. Single-Molecule Techniques: A Laboratory Manual Cold Spring Harbor, NY: Cold Spring Harbor Lab. Press
  101. Sexton AN, Regalado SG, Lai CS, Cost GJ, O'Neil CM. 100.  et al. 2014. Genetic and molecular identification of three human TPP1 functions in telomerase action: recruitment, activation, and homeostasis set point regulation. Genes Dev 28:1885–99 [Google Scholar]
  102. Sfeir A, Kosiyatrakul ST, Hockemeyer D, MacRae SL, Karlseder J. 101.  et al. 2009. Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication. Cell 138:90–103 [Google Scholar]
  103. Shim JW, Tan Q, Gu L-Q. 102.  2009. Single-molecule detection of folding and unfolding of the G-quadruplex aptamer in a nanopore nanocavity. Nucleic Acids Res 37:972–82 [Google Scholar]
  104. Smith FW, Feigon J. 103.  1992. Quadruplex structure of Oxytricha telomeric DNA oligonucleotides. Nature 356:164–68 [Google Scholar]
  105. Songyang Z, Liu D. 104.  2006. Inside the mammalian telomere interactome: regulation and regulatory activities of telomeres. Crit. Rev. Eukaryot. Gene Expr. 16:103–18 [Google Scholar]
  106. Stone MD, Mihalusova M, O'Connor CM, Prathapam R, Collins K, Zhuang X. 105.  2007. Stepwise protein-mediated RNA folding directs assembly of telomerase ribonucleoprotein. Nature 446:458–61 [Google Scholar]
  107. Theimer CA, Blois CA, Feigon J. 106.  2005. Structure of the human telomerase RNA pseudoknot reveals conserved tertiary interactions essential for function. Mol. Cell 17:671–82 [Google Scholar]
  108. Theimer CA, Feigon J. 107.  2006. Structure and function of telomerase RNA. Curr. Opin. Struct. Biol. 16:307–18 [Google Scholar]
  109. Theimer CA, Finger LD, Trantirek L, Feigon J. 108.  2003. Mutations linked to dyskeratosis congenita cause changes in the structural equilibrium in telomerase RNA. PNAS 100:449–54 [Google Scholar]
  110. Tinoco I Jr., Gonzalez RL Jr.. 109.  2011. Biological mechanisms, one molecule at a time. Genes Dev 25:1205–31 [Google Scholar]
  111. Tippana R, Xiao W, Myong S. 110.  2014. G-quadruplex conformation and dynamics are determined by loop length and sequence. Nucleic Acids Res 42:8106–14 [Google Scholar]
  112. van Oijen AM, Loparo JJ. 111.  2010. Single-molecule studies of the replisome. Annu. Rev. Biophys. 39:429–48 [Google Scholar]
  113. Verdun RE, Karlseder J. 112.  2007. Replication and protection of telomeres. Nature 447:924–31 [Google Scholar]
  114. Vulliamy TJ, Dokal I. 113.  2008. Dyskeratosis congenita: the diverse clinical presentation of mutations in the telomerase complex. Biochimie 90:122–30 [Google Scholar]
  115. Wang F, Podell ER, Zaug AJ, Yang Y, Baciu P. 114.  et al. 2007. The POT1–TPP1 telomere complex is a telomerase processivity factor. Nature 445:506–10 [Google Scholar]
  116. Wang H, Nora GJ, Ghodke H, Opresko PL. 115.  2011. Single molecule studies of physiologically relevant telomeric tails reveal POT1 mechanism for promoting G-quadruplex unfolding. J. Biol. Chem. 286:7479–89 [Google Scholar]
  117. Wang Y, Patel DJ. 116.  1993. Solution structure of a parallel-stranded G-quadruplex DNA. J. Mol. Biol. 234:1171–83 [Google Scholar]
  118. Watson JD. 117.  1972. Origin of concatemeric T7 DNA. Nat. New Biol. 239:197–201 [Google Scholar]
  119. Wenz C, Enenkel B, Amacker M, Kelleher C, Damm K, Lingner J. 118.  2001. Human telomerase contains two cooperating telomerase RNA molecules. EMBO J 20:3526–34 [Google Scholar]
  120. Wolna AH, Fleming AM, Burrows CJ. 119.  2014. Single-molecule analysis of thymine dimer-containing G-quadruplexes formed from the human telomere sequence. Biochemistry 53:7484–93 [Google Scholar]
  121. Wright WE, Shay JW. 120.  2001. Cellular senescence as a tumor-protection mechanism: the essential role of counting. Curr. Opin. Genet. Dev. 11:98–103 [Google Scholar]
  122. Wu JY, Stone MD, Zhuang X. 121.  2010. A single-molecule assay for telomerase structure-function analysis. Nucleic Acids Res 38:e16 [Google Scholar]
  123. Wu RA, Collins K. 122.  2014. Human telomerase specialization for repeat synthesis by unique handling of primer-template duplex. EMBO J 33:921–35 [Google Scholar]
  124. Wu RA, Dagdas YS, Yilmaz ST, Yildiz A, Collins K. 123.  2015. Single-molecule imaging of telomerase reverse transcriptase in human telomerase holoenzyme and minimal RNP complexes. eLife 4:e08363 [Google Scholar]
  125. Ying L, Green JJ, Li H, Klenerman D, Balasubramanian S. 124.  2003. Studies on the structure and dynamics of the human telomeric G quadruplex by single-molecule fluorescence resonance energy transfer. PNAS 100:14629–34 [Google Scholar]
  126. You H, Wu J, Shao F, Yan J. 125.  2015. Stability and kinetics of c-MYC promoter G-quadruplexes studied by single-molecule manipulation. J. Am. Chem. Soc. 137:2424–27 [Google Scholar]
  127. You H, Zeng X, Xu Y, Lim CJ, Efremov AK. 126.  et al. 2014. Dynamics and stability of polymorphic human telomeric G-quadruplex under tension. Nucleic Acids Res 42:8789–95 [Google Scholar]
  128. Zhou R, Zhang J, Bochman ML, Zakian VA, Ha T. 127.  2014. Periodic DNA patrolling underlies diverse functions of Pif1 on R-loops and G-rich DNA. eLife 3:e02190 [Google Scholar]
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