The genome of the cell is often exposed to DNA damaging agents and therefore requires an intricate wellregulated DNA damage response (DDR) to overcome its deleterious effects. The DDR needs proper regulation for its timely activation, repression, as well as appropriate choice of repair pathway. Studies in Saccharomyces cerevisiae have advanced our understanding of the DNA damage response, as well as the mechanisms the cell employs to maintain genome stability and how these mechanisms are regulated. Eukaryotic cells utilize post-translational modifications as a means for fine-tuning protein functions. Ubiquitylation and SUMOylation involve the attachment of small protein molecules onto proteins to modulate function or protein-protein interactions. SUMO in particular, was shown to act as a molecular glue when DNA damage occurs, facilitating the assembly of large protein complexes in repair foci. In other instances, SUMOylation alters a protein's biochemical activities, and interactions. SUMO-targeted ubiquitin ligases (STUbLs) are enzymes that target SUMOylated proteins for ubiquitylation and subsequent degradation, providing a function for theSUMO modification in the regulation and disassembly of repair complexes. Here, we discuss the major contributions of SUMO and STUbLs in the regulation of DNA damage repair pathways as well as in the maintenance of critical regions of the genome, namely rDNA regions, telomeres and the 2 μm circle in budding yeast.
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