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bioRxiv · 10.1101/2025.06.27.661970

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

Gonzalez, D. I.·Westerbeek, A. R.·Epum, E. A.·Friedman, K. L.
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Abstract

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 de novo telomere addition (dnTA), can be utilized. Yeast subtelomeric regions are hotspots of recombination, while interstitial telomere-like sites can promote dnTA. In yeast, dnTA sites, termed SiRTAs (Sites of Repair-associated Telomere Addition), require Cdc13 association. We identified the ubiquitin protease Ubp10 as a positive regulator of dnTA at SiRTAs. Loss of UBP10 reduces dnTA 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 RAD51 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 UBP10. This study highlights the diversity of DNA repair mechanisms at SiRTAs, advancing our understanding of telomere maintenance and chromosomal rearrangement formation. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=64 SRC="FIGDIR/small/661970v1_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@117336corg.highwire.dtl.DTLVardef@311ae3org.highwire.dtl.DTLVardef@1dc69b4org.highwire.dtl.DTLVardef@19fb195_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Gonzalez, D. I., Westerbeek, A. R., Epum, E. A., Friedman, K. L.. 2025-06-28. The ubiquitin protease Ubp10 suppresses the formation of translocations at Cdc13 binding sites. https://doi.org/10.1101/2025.06.27.661970

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