A STUbL wards off telomere fusions

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Protection of chromosomal ends from erroneous recognition as double‐strand breaks (DSBs) is critical for maintaining genome integrity. Unprotected ends can activate DNA repair pathways leading to catastrophic fusions or rearrangements of chromosomes. A study in The EMBO Journal identifies Uls1 as a new player in this end‐protection process, utilizing SUMO and ubiquitin modifications to prevent chromosomal fusions by clearing a polysumoylated form of Rap1. Telomeres, the ends of linear chromosomes, pose a tremendous challenge for eukaryotic cells, because their resemblance to DNA DSBs puts them at constant risk of being targeted by repair pathways. Thus, these ends must be kept off the radar of the two major DSB repair pathways, non‐homologous end joining (NHEJ) and homologous recombination (HR). A number of studies in the model system budding yeast previously identified a central role for the Rap1 protein in preventing NHEJ at telomeres. Rap1 is an evolutionarily conserved protein that binds to the double‐stranded DNA region of telomeres. It inhibits NHEJ via at least three different pathways (Marcand et al , 2008). Two of these are mediated by its binding partners Rif2 and Sir4, respectively, with a less well‐characterized third pathway independent of either interactor. How these pathways enable NHEJ evasion is not entirely clear, but recent findings of posttranslational modifications of telomere‐binding proteins, particularly by SUMO, hinted at a possible role for dynamic protein modifications in regulating telomeric functions. Attachment of the SUMO protein to a lysine residue in target proteins can change both their interaction profiles, by allowing other proteins to bind or impairing interactions, and their biochemical functions. Additionally, since the SUMO polypeptide itself contains lysines, poly‐SUMO chains can be generated, which …