Chromosome ends must be protected from repair machineries to avoid genomic instability. In yeast, the shelterin component Rap1 inhibits repair by non-homologous end-joining (NHEJ) at telomeres. Marcand and colleagues (EMBO J. http://doi.org/krj; 2013) have identified the SUMO-targeted ubiquitin ligase (STUbL) Uls1 as a key mediator of NHEJ inhibition at yeast telomeres, acting on SUMOylated Rap1.

The authors found that stationary yeast cells lacking Uls1 showed an increase in telomere–telomere fusions, a hallmark of aberrant telomeric NHEJ. Uls1 possesses translocase and ubiquitin ligase activities, and mutational analysis revealed that both were needed to prevent fusions. Furthermore, Uls1 localized to chromosome ends. SUMO mutations that prevent the accumulation of poly-SUMO chains rescued telomere fusions caused by loss of Uls1, suggesting that SUMOylated proteins perturb NHEJ inhibition. As published studies report a negative synthetic interaction between uls1 deletion and a hypomorphic allele of rap1, as well as SUMOylation of Rap1, the authors went on to investigate the role of Rap1 in Uls1 telomere function. Indeed, they found that mutation of Rap1 SUMOylation sites bypasses the requirement for Uls1 in NHEJ inhibition at telomeres, and that poly-SUMOylated Rap1 accumulates in the absence of Uls1. Thus, Uls1 acts to limit the accumulation of poly-SUMOylated Rap1. Although the precise role of Rap1 poly-SUMOylation remains unclear, the data suggest an inhibitory effect on a subset of pathways downstream of Rap1 in NHEJ inhibition.