The project aims at elucidating the molecular basis of two critical pathways that ensure tolerance to replication stress. In the first part, we will investigate the mechanism of how a conserved protease, SPRTN, contributes to the resolution of covalent and non-covalent protein-DNA interactions and address whether and how its functions are linked to the early embryonic death of Sprtn-/- mice. In the second part, we will elucidate the role of mammalian WRNIP1 protein in the replication of telomeric DNA. Taken together, these approaches will give insight into the molecular mechanisms that ensure faithful and complete duplication of problematic replication templates.
Molecular mechanisms of replication stress response