Identification of New Genes that Regulate Telomerase and Telomere Length in Budding Yeast

摘要

In budding yeast, Cdc13 has both an essential function in chromosome end protection as well as a non-essential role in telomere replication, by mediating recruitment of telomerase to the chromosome end. Using fusion protein techniques, we have determined that the essential function of Cdc13 is to deliver an Stnl-containing end protection complex to the telomere. This delivery is sufficient to protect the chromosome, but is unable to provide telomere replication. However, delivery of a small region of Cdc13 is capable of restoring telomerase recruitment in the absence of intact Cdc13 protein. In addition, we performed a genetic screen designed to identify hypothesized processing activities at telomeres. Several interesting mutants that were uncovered have been classified and their role in telomere maintenance is being analyzed. I am presently working in the biochemical characterization of the proteins involved in end protection, and in the identification of metazoan homologs of these proteins. It is our belief that the information derived from the experiments detailed in this proposal may be extrapolated to the corresponding biological situation in humans, where protection of chromosome ends is critical for maintaining genomic integrity and preventing genomic instability.