A DNA damage-induced SUMOylation wave simultaneously targets multiple DNA repair proteins.
Major finding: A DNA damage-induced SUMOylation wave simultaneously targets multiple DNA repair proteins.
Mechanism: Single-stranded DNA triggers collective SUMOylation of homologous recombination proteins.
Impact: SUMOylation acts as a “glue” to facilitate protein interactions and cellular processes like DNA repair.
A wide range of proteins are posttranslationally modified by covalent attachment of small ubiquitin-related modifier (SUMO) proteins. Single SUMOylation site mutants commonly lack discernible phenotypes even though SUMO itself is essential for viability; thus, the biologic significance and functional consequences of SUMOylation remain unclear for the vast majority of substrates. Because SUMO pathway mutants are highly sensitive to DNA double-strand breaks (DSB) and many homologous recombination (HR) components are SUMOylated, Psakhye and Jentsch evaluated the specificity and function of SUMOylation in this well-characterized DNA repair system in Saccharomyces cerevisiae. Surprisingly, quantitative mass spectrometry showed collective SUMOylation of HR proteins at multiple sites following DSB induction, indicating that the SUMO system can target a functionally related group of proteins in response to a specific stimulus. This observation was not restricted to the HR pathway, as UV light led to increased SUMOylation of components of the nucleotide excision repair pathway. The kinetics of SUMOylation after DSB induction was nearly identical for each protein, suggesting that SUMOylation occurs in a synchronous wave. Collective SUMOylation of HR proteins was catalyzed by a DNA-bound SUMO ligase that interacts with a component of the HR-initiating complex responsible for forming single-stranded DNA, which acted as the trigger for the SUMOylation wave. SUMOylation promoted physical interactions between HR proteins, and a mutant strain lacking multiple SUMOylation sites within core repair proteins showed slowed growth and delayed HR following DNA damage. These findings suggest a model whereby physical interactions between proteins in a shared pathway can be potentiated by collective SUMOylation in response to specific stimuli and imply that individual SUMOylation events interact in an additive manner to promote efficient DNA repair.