Structural analysis of the SUMO conjugation pathway

Post-translational protein modification by ubiquitin or ubiquitin-like modifiers (Ub/Ubl) regulates a whole variety of cellular processes (protein degradation, signaling, sorting, localization, activation and repression). In our project we aim to study different mechanisms of regulation of the Ub/Ubl pathway at different stages of the pathway: interaction E1-E2 enzymes; the regulation of the SUMO E3 ligase activity of Nse2, which is a subunit of the Smc5-Smc6 complex; and the regulatory mechanism of the de-ubiquitinase activity of USPL1. Smc5-Smc6 complex is involved in a variety of DNA repair pathways and participates in DNA double-stranded break repair. Disruption of SUMO conjugation by Smc5-Smc6-Nse2 produces serious problems in models of DNA damage.