End‐joining inhibition at telomeres requires the translocase and polySUMO‐dependent ubiquitin ligase Uls1 |
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| Authors: | Rachel Lescasse Sabrina Pobiega Isabelle Callebaut Stéphane Marcand |
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| Affiliation: | 1. 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;2. CNRS, UMR 217, , Fontenay‐aux‐roses, France;3. CNRS, UMR 7590, Institut de minéralogie et de physique des milieux condensés, Université Pierre et Marie Curie, , Paris, France |
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| 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. |
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| Keywords: | NHEJ STUbL SUMO telomere |
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