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Telomeres and Telomerase Chairman: Sydney Brenner, 1997 Telomeres are the protective genetic elements located at the ends of chromosomes and are essential for correct chromosomal structure and function. They are not fully replicated by the conventional DNA polymerase system because DNA synthesis occurs only in the 5' to 3' direction and requires an RNA primer for initiation. Consequently, cells require a special enzyme to maintain the telomeric ends of chromosomes during each round of replication. This enzyme, telomerase, is a ribonucleoprotein that extends chromosome ends by adding short stretches of nucleotide repeats using a portion of its integral RNA component as the template. Recently, much excitement has been generated by the suggestion that telomerase, or rather the absence of telomerase and the resultant loss of terminal DNA, is a cause of human ageing. The evidence for this is twofold: the telomeres of certain cells in culture shorten during their lifespan; and immortalization of cells is associated, at least in some cases, with the maintenance of telomeres and telomerase activity. The latter observation prompted the analysis of clinical samples from patients with cancer and the demonstration that, in contrast to normal somatic cells, malignant cells possess telomerase activity. This is a unique book. Not only does it contain the latest experimental results from an international group of experts, but it also includes critical examinations of the current evidence, and discussions that attempt to identify the central and underlying concepts of this rapidly expanding field.

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.