Role of the Telomere End Protection Complex in Telomere Maintenance

摘要

Telomeres are the protective ends of chromosomes that are necessary for maintaining the viability of a cell and the integrity of its genome. One essential function of telomeres is to protect the chromosome end from being degraded by nucleases that are normally present in any cell. Unprotected chromosome ends could fuse to each other leading to loss of genetic material, genomic instability, and subsequent carcinogenesis. The focus of my research is to understand the mechanism of chromosome end protection in the well-studied model organism, S. cerevisiae, and then extend the knowledge we gain in yeast to humans by identifying human homologues of the essential proteins involved in end protection. Using molecular and phylogenetic approaches, I have successfully identified yeast homologues of three proteins known to be involved in end protection - Cdc13, Stnl and Tenl. With these homologues in hand, I have initiated searches for human homologues of Stnl and Tenl. Using a combination of bioinformatics and yeast genetics, I have potentially identified a site of interaction between Cdc13 and Stnl that is essential for mediating end protection. These findings have further elucidated the mechanism of end protection and have allowed us to start looking for similar proteins and parallel mechanisms in humans.