Telomeres

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