Life at the end of the chromosome: Telomeres and telomerase

Abstract

Telomerase is the enzyme that replicates the ends of linear chromosomes, such as those found in human cells. Its absence has been implicated in cellular aging, and its reactivation promotes tumorigenesis. Telomerase is an unusual enzyme in that it contains an essential RNA subunit as well as protein components. Although the RNA component was described a decade ago, the first catalytic protein subunit of telomerase was discovered only recently through studies of a ciliated protozoan. Euplotes aediculatus. Computer searching and biochemical experiments then led to the identification of the genes for the corresponding telomerase subunits in yeast and humans. These proteins-comprise a new branch of the polymerase family called TERT (telomerase reverse transcriptase), distantly related to the enzyme responsible for copying the RNA of HIV (human immunodeficiency virus) and other retroviruses. The pathway by which TERT is assembled with the RNA subunit to form telomerase and the mechanism of chromosome end-replication are topics of current research. In addition, the identification of TERT provides a new focus for the development of inhibitors with promise as antitumor agents.