DNA damage-induced ubiquitylation:emerging regulators enforce protective mechanisms

Abstract

Our genome contains, in the form of DNA building blocks, the necessary information for orchestrating all cellular functions and ensuring species continuity. However, though being chemically stable, our DNA is under constant assault by various endogenous or exogenous sources. To counteract the perils arising due to DNA damage and to ensure genome integrity, life has evolutionarily acquired an arsenal of protective mechanisms, amongst which prominent is DNA repair. Depending on the nature of the inflicted DNA damage, specialised DNA repair pathways are activated in order to restore the original genetic information. During this work I focused on the elucidation of DNA repair- or other cytoprotective-mechanisms ensuing upon the induction of primarily DNA Double Strand Breaks (DSBs) or secondarily helix-distorting lesions. DSBs are mainly repaired by two pathways: error-prone Non-Homologous End-Joining (NHEJ) and error-free Homologous Recombination (HR). On the other hand, helix-distorting lesions, such as those arising due to UV-irradiation or cisplatin-induced mono-adducts, are rectified by Nucleotide Excision Repair (NER). More specifically, I put emphasis on the role of protein-ubiquitylation, a widespread protein Post-Translational Modification (PTM), in the spatiotemporal regulation of an efficient DSB response.