Telomerases

This book is a comprehensive and up-to-date review and evaluation of the contemporary status of telomerase research. Chapters in this volume cover the basic structure, mechanisms, and diversity of the essential and regulatory subunits of telomerase. Other topics include telomerase biogenesis, transcriptional and post-translational regulation, off-telomere functions of telomerase and the role of telomerase in cellular senescence, aging and cancer. Its relationship to retrotransposons, a class of mobile genetic elements that shares similarities with telomerase and serves as telomeres in selected organisms, are also reviewed.

Preface vii

Contributors ix

1 The Telomerase Complex: An Overview 1
Johanna Mancini and Chantal Autexier

2 Telomerase RNA: Structure, Function, and Molecular Mechanisms 23
Yehuda Tzfati and Julian J.-L. Chen

3 TERT Structure, Function, and Molecular Mechanisms 53
Emmanuel Skordalakes and Neal F. Lue

4 Telomerase Biogenesis: RNA Processing, Trafficking, and Protein Interactions 79
Tara Beattie and Pascal Chartrand

5 Transcriptional Regulation of Human Telomerase 105
Antonella Farsetti and Yu-Sheng Cong

6 Telomerase Regulation and Telomere-Length Homeostasis 135
Joachim Lingner and David Shore

7 Telomere Structure in Telomerase Regulation 157
Momchil D. Vodenicharov and Raymund J. Wellinger

8 Off-Telomere Functions of Telomerase 201
Kenkichi Masutomi and William C. Hahn

9 Murine Models of Dysfunctional Telomeres and Telomerase 213
Yie Liu and Lea Harrington

10 Cellular Senescence, Telomerase, and Cancer in Human Cells 243
Phillip G. Smiraldo, Jun Tang, Jerry W. Shay, and Woodring E. Wright

11 Telomerase, Retrotransposons, and Evolution 265
Irina R. Arkhipova

Index 301

NEAL F. LUE, MD, PHD, is Professor in the Department of Microbiology and Immunology at Weill Cornell Medical College. He received his BS from Johns Hopkins University and his MD and PhD from Stanford University. His laboratory studies the structures and mechanisms of the telomere and telomerase complexes in a variety of fungal model systems.

CHANTAL AUTEXIER, PHD, is Professor in the Department of Anatomy and Cell Biology and the Department of Medicine at McGill University. She received her BSc from Concordia University and her PhD from McGill University. Her laboratory studies the mechanisms that regulate telomerase and telomere functions in mammalian cells, and evaluates the principles of anticancer strategies that target these mechanisms.

Explores the structure, function, and emerging applications of telomerases

With contributions from leading experts and pioneers in the field, this book offers a comprehensive review of telomerase structure and function in a variety of organisms, including yeasts, ciliates, plants, and mammals. Chapters provide integrated discussions that examine the connections between the chemistry, biology, and emerging clinical applications of the telomerase enzyme. In particular, readers will gain new insights into the role of telomerases in cellular senescence, aging, and cancer.

Telomerases begins with an overview of the telomerase complex, followed by in-depth discussions of the chemistry of its two critical components: TERT and TER. Next, the book brings readers up to date with our current understanding of telomerases, including:

• Biological regulatory mechanisms that control the synthesis and assembly of the telomerase complex
• Regulations imposed by the nucleoprotein complex at chromosome ends
• Studies underscoring the role of the telomerase enzyme as a promising target and a useful tool in medical interventions

The book concludes with an essay that places the telomerase enzyme in an evolutionary context, illustrating its place within the highly diverse family of reverse transcriptases.

Telomerases is recommended for biochemists, enzymologists, protein scientists, cancer researchers, biophysicists, geneticists, and cell, molecular, and chromosome biologists. Explaining what the latest research in the field reveals about the structure and function of telomerases and how this research has informed investigations into their clinical applications, the book points to future avenues of research that will enable us to better understand the chemistry, biology, and clinical applications of telomerases.