2008 Eighth Annual Beckman Scholars Symposium
Friday Poster Session - July 28, 2006

This study aims to elucidate the roles of two kinases, Tel1 and Mec1, in the opening and closing of telomeres in Saccharomyces cerevisiae. Homologs for these two kinases have been found in humans, and they are being critically examined for possible sites of cancer therapies. The challenges in studying these two kinases are that their functions are partially redundant and they have a variety of roles in the cell. In addition to their roles in telomere maintenance, Tel1 and Mec1 also play a vital role as checkpoint proteins that respond to DNA damage. Large scale deletions of the TEL1 gene were made on plasmids that were transformed in a tel1 knockout strain so that native telomere lengths could be observed; strains lacking either the 3’, middle, or 5’ fragment maintained shorter but stable telomeres, which is analogous to the phenotype of a complete tel1 knockout, when compared to wild-type. In addition, de novo telomere addition assays were conducted in a tel1 knockout strain and a mec1 knockout strain. While loss of MEC1 did not have any observable effects on the kinetics of telomere addition, loss of TEL1 completely halted de novo telomere addition. This evidence suggests that Tel1 is playing a role in interchanging the telomere between its open and closed conformations as well as possibly some additional roles in telomere maintenance. It is also possible that Mec1 is involved in the process of opening the telomere as the absence of a participant in opening the telomere would not disrupt telomere addition in a de novo telomere addition assay where the telomere is artificially opened. Therefore, additional studies need to be conducted in order to decipher the true roles of these kinases in the opening and closing of telomeres including the creation of a library of tel1 and mec1 mutants with separation-of-function alleles that cause a loss telomere function but maintain these kinases’ ability to act as checkpoint proteins.