Updated publication reference for PubMed record(s): 31676685. Posttranslational modification by the small ubiquitin-like modifier Sumo regulates many cellular processes including the adaptive response to various types of stress, which has been referred to as Sumo Stress Response (SSR). However, it remains unclear whether the SSR involves a common set of core proteins regardless of the type of stress, or whether each particular type of stress induces a stress-specific SSR that targets a unique, largely non-overlapping set of Sumo substrates. In this study we used mass spectrometry to identify differentially sumoylated proteins during heat shock, hyperosmotic stress, oxidative stress, nitrogen starvation and DNA alkylation in Saccharomyces cerevisiae. Our results show that each stress triggers a specific SSR signature centered on proteins involved in transcription, translation, and chromatin regulation. Strikingly, while the various stress-specific SSRs were largely non-overlapping, all types of stresses tested here resulted in desumoylation of subunits of RNA polymerase III, which correlated with a decrease in tRNA synthesis. We conclude that desumoylation and subsequent inhibition of RNA polymerase III constitutes the core of all stress-specific SSRs.