Exploring the function of the CST complex at DNA double-strand breaks

DNA double-strand breaks (DSBs) are cytotoxic lesions that must be repaired to preserve genomic integrity. Following DSBs, cells activate a signal transduction pathway, known as DNA damage checkpoint, whose apical checkpoint kinases are Tel1 (ATM in humans) and Mec1 (ATR in humans). In Saccharomyces cerevisiae, these checkpoint kinases, once activated, promote DNA damage repair and support DNA replication under stress conditions1. The Cdc13-Stn1-Ten1 (CST) complex is known to be involved in telomere maintenance2. Interestingly, we found that the lack of Stn1 C terminus exacerbates the DNA damage sensitivity of mec1 and tel1 mutant cells, whereas a stn1 missense mutation suppresses it, suggesting a role for this protein in supporting the functions of these checkpoint kinases in DNA damage repair. We will investigate the molecular mechanisms of these genetic interactions to understand the role of Stn1 in checkpoint activation.