In this project, we propose to investigate the mechanisms that distinguish chromosome ends from DNA double-strand breaks. We will employ genetic and biochemical approaches to identify the factors that interact with the telomere protein Rap1 in fission yeast and gain a better understanding of how non-homologous end-joining is normally prevented at telomeres. In parallel, we will analyse the composition of mammalian repair complexes at telomeric and non-telomeric DNA ends and elucidate the role of the shelterin component TRF2 in the inhibition of the end-joining pathway. Finally, we will address the impact of nutrient status on telomere stability.
The mechanism of telomere protection by shelterin proteins