Grant: Operating Grant

Telomerase is an essential enzyme that ensures genome stability by replenishing the special DNA sequence repeats at the ends of eukaryotic chromosomes, the telomeres. Two components are required for telomerase activity in vitro: a protein that is believed to work like other enzymes that synthesize DNA using an RNA template, and such an RNA template molecule that harbours a specific sequence element that is used for sequence copying. Inadequate expression, maturation, modification of subunits and/or regulation of telomerase components is associated with a number of human disease states, foremost cancer, but also dyskeratosis congenita (DKC). In fact, it has been shown that DKC can be caused by mutations in the RNA component of telomerase. Using budding yeast as a model system, here we propose to investigate the biology of the yeast telomerase RNA. In particular, we wish to determine all the components of the yeast telomerase, learn more about how the RNA is regulated and localized and how the enzyme operates at its most important location, namely the catalytic center. Given the fact that telomerase function and regulation generally is very highly conserved across many species, including humans, we speculate that these studies provide critical clues and input into questions how this enzyme affects human health.