Structural Biology of Telomerase and Associated Factors

Telomerase ribonucleoprotein (RNP) plays a crucial role in maintaining telomere length by processively adding telomeric repeats to the 3' ends of chromosomes. Telomerase activation is linked to cancer, while mutations that compromise telomerase function result in diseases such as dyskeratosis congenita. The synthesis of telomeric repeats necessitates two core telomerase components: telomerase reverse transcriptase (TERT) and telomerase RNA (TER). However, cellular telomerase holoenzymes encompass a diverse range of protein factors, both constitutively and transiently interacting. These factors are integral to telomerase assembly or regulation at telomeres. This review emphasizes recent advancements in structural studies of telomerase holoenzymes and their associated factors from Tetrahymena thermophila, Saccharomyces cerevisiae, Schizosaccharomyces pombe, and humans. These studies have significantly deepened our molecular understanding not only of the mechanism underlying telomeric repeat synthesis but also of the biological roles of telomerase-associated proteins.