Telomerases: Chemistry, Biology, and Clinical Applications

Explores the structure, function, and emerging applicationsof telomerases

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

Telomerases begins with an overview of the telomerasecomplex, followed by in–depth discussions of the chemistry of itstwo critical components: TERT and TER. Next, the book bringsreaders up to date with our current understanding of telomerases,including:

Biological regulatory mechanisms that control the synthesis andassembly of the telomerase complex Regulations imposed by the nucleoprotein complex at chromosomeends Studies underscoring the role of the telomerase enzyme as apromising target and a useful tool in medical interventions

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

Telomerases is recommended for biochemists,enzymologists, protein scientists, cancer researchers,biophysicists, geneticists, and cell, molecular, and chromosomebiologists. Explaining what the latest research in the fieldreveals about the structure and function of telomerases and howthis research has informed investigations into their clinicalapplications, the book points to future avenues of research thatwill enable us to better understand the chemistry, biology, andclinical applications of telomerases.

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 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 ofMicrobiology and Immunology at Weill Cornell Medical College. Hereceived his BS from Johns Hopkins University and his MD and PhDfrom Stanford University. His laboratory studies the structures andmechanisms of the telomere and telomerase complexes in a variety offungal model systems.

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