While telomerase activity is undetectable in most human cells, high levels of telomerase activity is a hallmark of the majority of cancers. The genetically tractable model organism Saccharomyces cerevisiae has provided many insights into telomerase biology. Chromatin immunoprecipitation (ChlP) experiments performed in the Zakian laboratory provided a model for the regulation of telomerase activity in S. cerevisiae. The """"""""activation"""""""" model of telomerase regulation describes the association of components of the telomerase holoenzyme with the telomere during the cell cycle. Interaction between the holoenzyme components Estlp and the telomerase templating RNA is a key contact that is required for the association of Est1 p with the catalytic subunit (Est2p) at the telomere. The association of Estlp with the telomere coincides with active Est2p lengthening of telomeres in late S-phase. Although the N-terminus of Est1 is relatively well conserved in humans and the fission yeast, Schizosaccharomyces pombe, the C-terminal RNA binding domain is found only in S. cerevisiae. This finding, and other similarities between human and S. pombe telomere-associated proteins, suggests that the model for telomerase regulation in S. cerevisiae may not be universally applicable. Thus, ChlP experiments will be performed to dissect the association of the S. pombe telomerase holoenzyme and the telomere. To perform analogous experiments in S. pombe, the telomerase RNA will first be identified and characterized. The completion of these experiments will provide a framework for the regulation of telomerase activity that may be relevant to human telomerase biology.
