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

Abstract

Abstract : In budding yeast, previous work has shown that 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. The exact molecular mechanism by which Cdc13 protects the telomere has not been elucidated, although Stn1, a protein previously shown to interact with Cdc13, may contribute to end protection. Using fusion protein techniques, we have determined that the essential function of Cdc13 is to deliver an Stn1-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 ofCdcl3 is capable of restoring telomerase recruitment in the absence of intact Cdc13 protein. In addition, we have begun a genetic screen designed to identify the hypothesized processing activity at telomeres and have uncovered several interesting mutants which are awaiting characterization. Several other experiments designed to further our understanding of the protein complex providing end protection in yeast are in progress. 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.