Telomeres

Carole Saintomé is Assistant Professor in Biochemistry at Sorbonne Université, France. She studies the role of single-stranded DNA binding proteins at telomeres and their interactions with G-quadruplexes DNA structures at the Muséum national d'Histoire naturelle, France.

• Foreword xiiiJulia COOPERChapter 1 Telomeres: All's Well That Ends Well 1Patrizia ALBERTI1.1 Introduction 11.2 The beginning of the end 21.3 Telomeric architectures: from ciliates to other eukaryotes 101.4 G-quadruplexes at telomeres 181.5 References 26Chapter 2 Methods to Measure Telomere Lengths 39Lauréline ROGER2.1 Why does telomere length matter? 392.2 Methods for measuring telomere length 412.3 References 53Chapter 3 The Shelterin Complex 57Claire GHILAIN, Eric GILSON and Marie-Josèphe GIRAUD-PANIS3.1 TRF1 and TRF2, structurally alike but… 593.2 RAP1 753.3 TIN2 793.4 TPP1-POT1 823.5 Quaternary structure of the shelterin 863.6 Concluding remarks 863.7 References 87Chapter 4 Mammalian Telomere Organization and Dynamics in the Nuclear Volume 105Sonia STINUS and Laure CRABBE4.1 Introduction 1054.2 Nuclear envelope and lamins: orchestrators of cell and genome architecture 1064.3 Interplay between telomeres and nuclear structures 1084.4 Telomere tethering to the NE to promote meiotic pairing 1094.5 Telomere organization and dynamics in the nucleus 1104.6 Interaction between telomere chromatin and lamins during post-mitotic nuclear assembly 1114.7 Interaction between telomere chromatin and lamins for telomere maintenance 1124.8 Conclusion 1134.9 References 114Chapter 5 Saccharomyces cerevisiae, a Model at the Forefront of Telomere Biology 119Aurélia BARASCU and Maria Teresa TEIXEIRA5.1 Introduction 1195.2 Telomere characterization: various experimental organisms for first historical experiments 1215.3 Protection and proliferation: the telomere dilemma 1225.4 Telomere maintenance 1295.5 Telomeres: one size for one identity 1345.6 Telomeres, replicative senescence, aging and genomic instability 1365.7 Senescence escape phenomena and genomic instability 1405.8 Conclusion 1425.9 References 142Chapter 6 Dealing with Replication Stress at Telomeres 157Stéphane COULON6.1 Introduction 1576.2 Removal of the DNA structures that impede RF progression 1626.3 Accessory factors that contribute to telomere replication l 1716.4 Concluding remarks 1766.5 References 177Chapter 7 A Brief History of Telomerase: Exceptional Women in Command 193Vincent GÉLI7.1 Acknowledgments 1997.2 References 199Chapter 8 Telomerase: Structure and Mechanism 205Carole SAINTOMÉ8.1 Introduction 2058.2 Roles 2068.3 Structures 2078.4 Biogenesis 2128.5 Mechanism 2148.6 Regulation 2158.7 Disease and therapy 2168.8 Conclusion 2168.9 References 217Chapter 9 Alternative Lengthening of Telomeres 223Mathilde GAUCHIER9.1 ALT cell markers 2249.2 ALT mechanisms 2289.3 Replicative stress and DNA repair pathway at ALT telomeres 2299.4 The structure of chromatin at ALT telomeres 2309.5 ALT and cancer 2329.6 The ALT pathway: a non-pathological function? 2329.7 Alternative pathways not involving recombination: evolutionary aspects 2339.8 Appendix: experimental methods that allow the identification of the ALT phenotype in human cancer cells 2369.9 References 237Chapter 10 TERRA, Telomeric Non-coding RNAs 245Anabelle DECOTTIGNIES10.1 Introduction 24510.2 The human TERRAs 24610.3 The mouse TERRAs 25510.4 Conclusion 25810.5 References 258Chapter 11 Telomeres and Cancer 263Arturo LONDOÑO-VALLEJO11.1 Introduction 26311.2 Short telomeres and telomere-induced senescence are barriers to oncogenic development 26411.3 Excessive shortening of telomeres promotes CIN in the early stages of cancer transformation 26711.4 The contribution of telomere-driven CIN to tumor progression 27011.5 The senescent microenvironment promotes cancer development 27111.6 Mechanisms of cell immortalization 27311.7 Therapeutic potential of telomeres and telomerase and prognostic value of telomere-related evaluations 27711.8 Conclusion 27911.9 Acknowledgments 27911.10 References 280Chapter 12 Physiopathology of Telomeres 291Caroline KANNENGIESSER and Patrick REVY12.1 Introduction 29112.2 Telomere length in blood 29212.3 Different genes associated with telomere defects 29512.4 Different diseases associated with telomere defects 30012.5 Genetic analysis and counseling 30812.6 Treatment of diseases associated with telomere defects 31012.7 Compensatory somatic mutations in the TERT promoter 31112.8 Missing heredity 31212.9 Conclusion 31312.10 References 313Chapter 13 Telomeres Targeting Agents 329Sophie BOMBARD, Patrick MAILLIET and Marie-Paule TEULADE-FICHOU13.1 Introduction 32913.2 Chemistry and in vitro properties of G4 ligands targeting telomeres 33013.3 Biological properties of G4 ligands targeting telomeres 34113.4 Metal complexes targeting telomeres 34413.5 Compounds targeting the proteins of the human shelterin complex 34813.6 Compounds targeting telomerase 35513.7 General conclusion 35713.8 Acknowledgments 35813.9 References 358List of Authors 373Index 377