title: End-joining inhibition at telomeres requires the translocase and polySUMO-dependent ubiquitin ligase Uls1.
abstract: 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.
authors: CEA, Direction des sciences du vivant/Institut de radiobiologie cellulaire et moléculaire/Service instabilité génétique réparation recombinaison/Laboratoire télomère et réparation du chromosome, Fontenay-aux-roses, France.
authors: Rachel
authors: R
authors: Lescasse
authors: Sabrina
authors: S
authors: Pobiega
authors: Isabelle
authors: I
authors: Callebaut
authors: Stéphane
authors: S
authors: Marcand
mesh_terms: D059766:DNA End-Joining Repair; D004265:DNA Helicases / Q000378:metabolism / Q000502:physiology*; D015536:Down-Regulation; D030781:Organisms, Genetically Modified; D010458:Peptidyl Transferases / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding; D055503:Protein Multimerization / Q000502:physiology; D025842:SUMO-1 Protein / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism / Q000502:physiology; D058207:Sumoylation / Q000502:physiology; D016615:Telomere / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism / Q000502:physiology; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism
chemical_list: C061573:SIR4 protein, S cerevisiae; C099362:SMT3 protein, S cerevisiae; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D025841:Small Ubiquitin-Related Modifier Proteins; D010458:Peptidyl Transferases; D044767:Ubiquitin-Protein Ligases; C506745:ULS1 protein, S cerevisiae; D004265:DNA Helicases; D020827:rap1 GTP-Binding Proteins