The ubiquitin protease Ubp10 suppresses the formation of translocations at Cdc13 binding sites.

Double strand breaks (DSBs) pose a significant threat to chromosome stability and, if left unrepaired, can result in chromosome rearrangements. Canonical DNA repair pathways mitigate these risks. However, if these repair mechanisms fail to repair the DSB, alternative repair pathways, such as break-induced replication (BIR), single-strand annealing (SSA), and telomere addition (TA), can be utilized. Yeast subtelomeric regions are hotspots of recombination, while interstitial telomere-like sites can promote TA. In yeast, TA sites, termed SiRTAs (Sites of Repair-associated Telomere Addition), require Cdc13 association. We identified the ubiquitin protease Ubp10 as a positive regulator of TA at SiRTAs. Loss of reduces TA frequency but increases the frequency of other chromosomal rearrangements at SiRTAs. SiRTAs utilize the repetitive subtelomeric regions of donor chromosomes to facilitate rearrangements, with a fraction occurring independently of and requiring Sir4 and Sir2 components of the SIR complex. Association of Cdc13 with the SiRTA is necessary and sufficient to stimulate translocations in the absence of . This study highlights the diversity of DNA repair mechanisms at SiRTAs, advancing our understanding of telomere maintenance and chromosomal rearrangement formation.