The maintenance of genomic integrity is a crucial biological process. Among the main factors influencing genome stability are DNA repair mechanisms, which are highly conserved among eukaryotes. There is a complex interplay and crosstalk among the different regulatory mechanisms that control DNA repair pathways. These mechanisms often exploit post-translational modifications such as ubiquitination and sumoylation. The recent discovery of the evolutionarily conserved family of SUMO-targeted Ubiquitin ligases (STUbL) has established a novel mode of communication between the sumoylation and ubiquitination pathways. In addition, recent evidence has implicated the sumoylation pathway and STUbLs as important players contributing to subnuclear architecture. This project aims to understand the mechanisms by which ubiquitination/sumoylation, subnuclear localization and DNA repair interface to maintain genome integrity. Recent data from the Gasser lab has identified the relocalization of damage to nuclear pores as a novel event that contributes to repair by a complex of nuclear pores and Slx5-Slx8 (the budding yeast STUbL). This proposal will focus on the characterization of molecular mechanism through which Slx5-Slx8 regulates DNA repair. We want to understand how ubiquitin/SUMO modification affects eukaryotic nuclear organization during DNA repair. We combine yeast molecular genetics, biochemical methods and quantitative live fluorescence imaging approaches to address these questions at a molecular level.
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