Telomeres are essential for the maintenance of chromosome stability. In the absence of telomere function, chromosome ends fuse and progressive genomic rearrangements occur. In most eukaryotes, telomeres consist of tandem copies of simple sequences repeats. These telomere repeats are synthesized de novo onto chromosomes ends by the enzyme telomerase. Telomerase is a specialized DNA polymerase first identified in Tetrahymena. The enzyme contains an essential RNA component that provides the template for telomere repeat synthesis. Since its initial identification, telomerase activity and the RNA components have been characterized from a variety of eukaryotes. In humans, telomerase is activated during tumor growth and evidence suggests it may be a good target for cancer chemotherapy. Recently, telomerase protein components have been identified from Tetrahymena, Euplotes yeasts, and human cells. Although some of the protein components are conserved across species, it appears that not all of the telomerase components will be conserved. To take advantage of the well characterized reaction mechanism and the known structure of the RNA component, we are continuing to analyze function of the Tetrahymena telomerase enzyme. We will use the RNA component to probe the structure and function of the telomerase RNP. The protein components of telomerase will be further characterized and we will test their function in vitro and in vivo. Finally, we will take advantage of the unique biology of Tetrahymena to identify new components that are important in telomere maintenance.
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