In contrast to our extensive knowledge on covalent SUMO target proteins, we are limited in our understanding of proteins that bind SUMO family members in a non-covalent manner. We have identified interactors of different SUMO isoforms: monomeric SUMO1, monomeric SUMO2 or linear trimeric SUMO2 chains, using a mass spectrometry-based proteomics approach. We identified 382 proteins that bind to different SUMO isoforms mainly in a preferential manner. Interestingly, XRCC4 was the only DNA repair protein in our screen with a preference for SUMO2 trimers over mono-SUMO2 as well as the only protein in our screen that belongs to the Non-Homologous End Joining (NHEJ) DNA double-strand break repair pathway. A functional SIM in XRCC4 regulated its recruitment to local sites of DNA damage and its phosphorylation in S320 by DNA-PKcs. Combined, our data highlight the importance of non-covalent and covalent sumoylation for DNA double-strand break repair via the NHEJ pathway and provides a resource of SUMO isoform interactors.