TELOSTAB

Telomeres cap native chromosome ends by preventing them from being recognized and processed as chromosomal break ends. This core telomere function is a cornerstone of chromosome stability. Failure to cap telomeres results in chromosome fusions whose mitotic instability leads to catastrophic mutational processes. The rarity of these events relies on an efficient telomere capping established by a limited set of proteins present at telomeres. Full telomere protection is the result of a synergy between several co-existing mechanisms that buffer each other. Despite two decades of studies, the molecular mechanisms acted by telomere factors are still poorly understood today. To tackle this issue, we address the individual molecular mechanisms of telomere protection using two complementary and experimentally amenable model systems: (i) budding yeast Saccharomyces cerevisiae to resolve the full spectrum of telomere protection pathways against fusions and (ii) fission yeast Schizosaccharomyces pombe to explore commonalities among species and forand for its high degree of conservation with human telomere proteins. We will do this by (i) dissecting each pathway in isolation from the others and (ii) combining a large set of complementary state-of-the-art in vivo and in vitro approaches.