Biogenesis and Regulation of Telomerase during Development and Cancer.

Telomerase is a large ribonucleoprotein complex responsible for the addition of telomeric DNA repeats to chromosomal ends. Telomerase is composed of core and accessory components that work in coordination to ensure telomere length is maintained during development and in specific cell types. Telomerase activity is tightly regulated and is strongly increased in most tumor cells. On the other hand, loss-of-function mutations either in accessory factors or in core components of the complex impact telomere maintenance and cause a large spectrum of severe phenotypes, typically described as telomere biology disorders. A central element for efficient telomerase function is the proper biogenesis and assembly of the holoenzyme. Here, we discuss our current understanding of these processes and how they modulate telomerase efficiency. We consider how these processes are influenced by the specific subcellular localization of different telomerase components during different stages of the assembly of the holoenzyme. We describe the tremendous progress made in this area over the last decade and how recently discovered aspects of telomerase biogenesis can be exploited clinically, to actively benefit patients suffering from telomere biology disorders.