Composition and function of telomeric multi-protein complexes and their regulation by ADP-ribosylation

Telomere maintenance is vital to genome stability. The Shelterin complex, composed of six different proteins, protects telomeres from an illicit DNA damage response and orchestrates telomere extension by telomerase. The precise
mechanisms of telomere protection and length homeostasis are incompletely understood. How does the cell navigate the dilemma that chromosome termini are sequestered from the DNA-damage sensing machinery to avoid lethal
chromosome fusions whilst needing to be exposed to telomerase for telomere extension? In human cells, the ADPribosyltransferase tankyrase modifies Shelterin to enable telomerase-dependent telomere extension, presumably by
modulating Shelterin stoichiometry. In this project, we aim to combine biochemical, biophysical, single-molecule fluorescence and cell-based studies to understand the relevance and regulation of Shelterin complex stoichiometry
in telomere protection and length homeostasis.