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p>Foreword xiii<br /><i>Julia COOPER</i> <p><b>Chapter 1 Telomeres: All’s Well That Ends Well 1</b><br /><i>Patrizia ALBERTI</i></p> <p>1.1 Introduction 1</p> <p>1.2 The beginning of the end 2</p> <p>1.3 Telomeric architectures: from ciliates to other eukaryotes 10</p> <p>1.4 G-quadruplexes at telomeres 18</p> <p>1.5 References 26</p> <p><b>Chapter 2 Methods to Measure Telomere Lengths 39</b><br /><i>Lauréline ROGER</i></p> <p>2.1 Why does telomere length matter? 39</p> <p>2.2 Methods for measuring telomere length 41</p> <p>2.3 References 53</p> <p><b>Chapter 3 The Shelterin Complex 57</b><br /><i>Claire GHILAIN, Eric GILSON and Marie-Josèphe GIRAUD-PANIS</i></p> <p>3.1 TRF1 and TRF2, structurally alike but… 59</p> <p>3.2 RAP1 75</p> <p>3.3 TIN2 79</p> <p>3.4 TPP1-POT1 82</p> <p>3.5 Quaternary structure of the shelterin 86</p> <p>3.6 Concluding remarks 86</p> <p>3.7 References 87</p> <p><b>Chapter 4 Mammalian Telomere Organization and Dynamics in the Nuclear Volume 105</b><br /><i>Sonia STINUS and Laure CRABBE</i></p> <p>4.1 Introduction 105</p> <p>4.2 Nuclear envelope and lamins: orchestrators of cell and genome architecture 106</p> <p>4.3 Interplay between telomeres and nuclear structures 108</p> <p>4.4 Telomere tethering to the NE to promote meiotic pairing 109</p> <p>4.5 Telomere organization and dynamics in the nucleus 110</p> <p>4.6 Interaction between telomere chromatin and lamins during post-mitotic nuclear assembly 111</p> <p>4.7 Interaction between telomere chromatin and lamins for telomere maintenance 112</p> <p>4.8 Conclusion 113</p> <p>4.9 References 114</p> <p><b>Chapter 5 Saccharomyces cerevisiae, a Model at the Forefront of Telomere Biology 119</b><br /><i>Aurélia BARASCU and Maria Teresa TEIXEIRA</i></p> <p>5.1 Introduction 119</p> <p>5.2 Telomere characterization: various experimental organisms for first historical experiments 121</p> <p>5.3 Protection and proliferation: the telomere dilemma 122</p> <p>5.4 Telomere maintenance 129</p> <p>5.5 Telomeres: one size for one identity 134</p> <p>5.6 Telomeres, replicative senescence, aging and genomic instability 136</p> <p>5.7 Senescence escape phenomena and genomic instability 140</p> <p>5.8 Conclusion 142</p> <p>5.9 References 142</p> <p><b>Chapter 6 Dealing with Replication Stress at Telomeres 157</b><br /><i>Stéphane COULON</i></p> <p>6.1 Introduction 157</p> <p>6.2 Removal of the DNA structures that impede RF progression 162</p> <p>6.3 Accessory factors that contribute to telomere replication l 171</p> <p>6.4 Concluding remarks 176</p> <p>6.5 References 177</p> <p><b>Chapter 7 A Brief History of Telomerase: Exceptional Women in Command 193</b><br /><i>Vincent GÉLI</i></p> <p>7.1 Acknowledgments 199</p> <p>7.2 References 199</p> <p><b>Chapter 8 Telomerase: Structure and Mechanism 205</b><br /><i>Carole SAINTOMÉ</i></p> <p>8.1 Introduction 205</p> <p>8.2 Roles 206</p> <p>8.3 Structures 207</p> <p>8.4 Biogenesis 212</p> <p>8.5 Mechanism 214</p> <p>8.6 Regulation 215</p> <p>8.7 Disease and therapy 216</p> <p>8.8 Conclusion 216</p> <p>8.9 References 217</p> <p><b>Chapter 9 Alternative Lengthening of Telomeres 223</b><br /><i>Mathilde GAUCHIER</i></p> <p>9.1 ALT cell markers 224</p> <p>9.2 ALT mechanisms 228</p> <p>9.3 Replicative stress and DNA repair pathway at ALT telomeres 229</p> <p>9.4 The structure of chromatin at ALT telomeres 230</p> <p>9.5 ALT and cancer 232</p> <p>9.6 The ALT pathway: a non-pathological function? 232</p> <p>9.7 Alternative pathways not involving recombination: evolutionary aspects 233</p> <p>9.8 Appendix: experimental methods that allow the identification of the ALT phenotype in human cancer cells 236</p> <p>9.9 References 237</p> <p><b>Chapter 10 TERRA, Telomeric Non-coding RNAs 245</b><br /><i>Anabelle DECOTTIGNIES</i></p> <p>10.1 Introduction 245</p> <p>10.2 The human TERRAs 246</p> <p>10.3 The mouse TERRAs 255</p> <p>10.4 Conclusion 258</p> <p>10.5 References 258</p> <p><b>Chapter 11 Telomeres and Cancer 263</b><br /><i>Arturo LONDOÑO-VALLEJO</i></p> <p>11.1 Introduction 263</p> <p>11.2 Short telomeres and telomere-induced senescence are barriers to oncogenic development 264</p> <p>11.3 Excessive shortening of telomeres promotes CIN in the early stages of cancer transformation 267</p> <p>11.4 The contribution of telomere-driven CIN to tumor progression 270</p> <p>11.5 The senescent microenvironment promotes cancer development 271</p> <p>11.6 Mechanisms of cell immortalization 273</p> <p>11.7 Therapeutic potential of telomeres and telomerase and prognostic value of telomere-related evaluations 277</p> <p>11.8 Conclusion 279</p> <p>11.9 Acknowledgments 279</p> <p>11.10 References 280</p> <p><b>Chapter 12 Physiopathology of Telomeres 291</b><br /><i>Caroline KANNENGIESSER and Patrick REVY</i></p> <p>12.1 Introduction 291</p> <p>12.2 Telomere length in blood 292</p> <p>12.3 Different genes associated with telomere defects 295</p> <p>12.4 Different diseases associated with telomere defects 300</p> <p>12.5 Genetic analysis and counseling 308</p> <p>12.6 Treatment of diseases associated with telomere defects 310</p> <p>12.7 Compensatory somatic mutations in the TERT promoter 311</p> <p>12.8 Missing heredity 312</p> <p>12.9 Conclusion 313</p> <p>12.10 References 313</p> <p><b>Chapter 13 Telomeres Targeting Agents 329</b><br /><i>Sophie BOMBARD, Patrick MAILLIET and Marie-Paule TEULADE-FICHOU</i></p> <p>13.1 Introduction 329</p> <p>13.2 Chemistry and in vitro properties of G4 ligands targeting telomeres 330</p> <p>13.3 Biological properties of G4 ligands targeting telomeres 341</p> <p>13.4 Metal complexes targeting telomeres 344</p> <p>13.5 Compounds targeting the proteins of the human shelterin complex 348</p> <p>13.6 Compounds targeting telomerase 355</p> <p>13.7 General conclusion 357</p> <p>13.8 Acknowledgments 358</p> <p>13.9 References 358</p> <p>List of Authors 373</p> <p>Index 377</p>

<p><b>Carole Saintomé</b> is Assistant Professor in Biochemistry at Sorbonne Université, France. She studies the role of singlestranded DNA binding proteins at telomeres and their interactions with G-quadruplexes DNA structures at the Muséum national d’Histoire naturelle, France.</p>

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