End-joining inhibition at telomeres requires the translocase and polySUMO-dependent ubiquitin ligase Uls1

• Published in: The EMBO journal Vol. 32; no. 6; pp. 805 - 815
• Main Authors: Lescasse, Rachel, Pobiega, Sabrina, Callebaut, Isabelle, Marcand, Stéphane
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 20.03.2013; Nature Publishing Group UK; Springer Nature B.V; EMBO Press; Nature Publishing Group
• Subjects: Biochemistry, Molecular Biology; Deoxyribonucleic acid; DNA; DNA End-Joining Repair; DNA Helicases - metabolism; DNA Helicases - physiology; Down-Regulation; EMBO13; EMBO31; Eukaryotes; Inhibition; Life Sciences; NHEJ; Organisms, Genetically Modified; Peptidyl Transferases - metabolism; Peptidyl Transferases - physiology; Protein Binding; Protein Multimerization - physiology; Proteins; rap1 GTP-Binding Proteins - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; Saccharomyces cerevisiae Proteins - physiology; Silent Information Regulator Proteins, Saccharomyces cerevisiae - metabolism; Silent Information Regulator Proteins, Saccharomyces cerevisiae - physiology; Small Ubiquitin-Related Modifier Proteins - metabolism; Small Ubiquitin-Related Modifier Proteins - physiology; STUbL; SUMO; SUMO-1 Protein - metabolism; Sumoylation - physiology; Telomerase; telomere; Telomere - metabolism; Ubiquitin-Protein Ligases - metabolism; Ubiquitin-Protein Ligases - physiology; Yeasts; SUMO; NHEJ; STUbL; telomere
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1038/emboj.2013.24

In eukaryotes, permanent inhibition of the non‐homologous end joining (NHEJ) repair pathway at telomeres ensures that chromosome ends do not fuse. In budding yeast, binding of Rap1 to telomere repeats establishes NHEJ inhibition. Here, we show that the Uls1 protein is required for the maintenance of NHEJ inhibition at telomeres. Uls1 protein is a non‐essential Swi2/Snf2‐related translocase and a Small Ubiquitin‐related Modifier (SUMO)‐Targeted Ubiquitin Ligase (STUbL) with unknown targets. Loss of Uls1 results in telomere–telomere fusions. Uls1 requirement is alleviated by the absence of poly‐SUMO chains and by rap1 alleles lacking SUMOylation sites. Furthermore, Uls1 limits the accumulation of Rap1 poly‐SUMO conjugates. We propose that one of Uls1 functions is to clear non‐functional poly‐SUMOylated Rap1 molecules from telomeres to ensure the continuous efficiency of NHEJ inhibition. Since Uls1 is the only known STUbL with a translocase activity, it can be the general molecular sweeper for the clearance of poly‐SUMOylated proteins on DNA in eukaryotes. A STUbL with DNA‐dependent ATPase activity protects telomeres by preventing accumulation of poly‐sumoylated Rap1 on chromosome ends.