Telomeres and telomerase: revealing the end game.

Because eukaryotic chromosomes are composed of linear DNA molecules, specialized mechanisms are required to ensure their protection and replication. Telomeres, consisting of multiple repeats of a simple DNA sequence and associated proteins, cap these chromosome ends. Telomeric DNA replication requires telomerase, a reverse transcriptase with an intrinsic RNA subunit that provides a template for synthesizing the DNA repeats. New technologies, including cryogenic electron microscopy and long-read DNA sequencing, have provided insights into telomere biology that motivate this review. Furthermore, mutations that impair the machinery responsible for the replication and protection of telomeres lead to telomere biology disorders, and activation of telomerase is a driver of diverse cancers. In this review, we describe how basic science is now informing therapeutic approaches to these diseases.