Telomere replication is mediated by a ribonucleoprotein complex called telomerase. While the RNA component of yeast and human telomerase have been cloned the protein components have not. Work initiated by Chuck Epstein in Dr. Zakian's labomtory on physical association between yeast EST1 proteins and telomerase RNA will serve as the initial starting point for experiments in Dr. Shay's laboratory. Dr. Epstein will help to clarify the role of EST1 as well as identify novel potential telomerase components, via their genetic interactions with a novel allele of EST1 recently discovered in the Zakian lab. As soon as is feasible the information obtained from the yeast model system will be applied to determine if proteins similar to EST1 can be identified in human cells. The utility of understanding telomerase structure in a genetic model such as yeast may contribute to our understanding of mammalian telomerase, and help in the development of telomerase targeting drugs. Since telomerase is frequently inactive in somatic cells, but activated in tumor cells, such drugs may have anti-tumor utility.