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

David I Gonzalez1, Allison R Westerbeek1, Esther A Epum1

  • 1Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, US.

Biorxiv : the Preprint Server for Biology
|July 16, 2025
PubMed

Insights

The ubiquitin protease Ubp10 regulates DNA repair at specific sites (SiRTAs) in yeast. Loss of Ubp10 reduces de novo telomere addition but increases chromosomal rearrangements, revealing complex repair pathway interactions.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Double strand breaks (DSBs) threaten chromosome stability and can lead to rearrangements if unrepaired.
  • Alternative DNA repair pathways, including break-induced replication (BIR), single-strand annealing (SSA), and de novo telomere addition (dnTA), are activated when canonical pathways fail.
  • Yeast subtelomeric regions are recombination hotspots, and interstitial telomere-like sites can promote dnTA.

Purpose of the Study:

  • To investigate the regulation of de novo telomere addition (dnTA) at Sites of Repair-associated Telomere Addition (SiRTAs) in yeast.
  • To identify factors that influence DNA repair pathway choice at SiRTAs.

Main Methods:

  • Genetic analysis of yeast strains with mutations in DNA repair genes.
  • Characterization of de novo telomere addition (dnTA) and chromosomal rearrangement frequencies at SiRTAs.
  • Investigating the role of the ubiquitin protease Ubp10 and the SIR complex in SiRTA-mediated repair.

Main Results:

  • The ubiquitin protease Ubp10 was identified as a positive regulator of dnTA at SiRTAs.
  • Loss of UBP10 decreased dnTA frequency but increased other chromosomal rearrangements at SiRTAs.
  • SiRTA-mediated rearrangements can occur independently of RAD51 and require SIR complex components (Sir4 and Sir2).
  • Cdc13 association with SiRTAs is crucial for stimulating translocations when UBP10 is absent.

Conclusions:

  • Ubp10 plays a critical role in directing DNA repair pathway choice at SiRTAs.
  • SiRTAs exhibit diverse DNA repair mechanisms, highlighting the complexity of telomere maintenance and chromosomal rearrangement formation.
  • This study advances the understanding of how cells manage DNA double-strand breaks and maintain genome integrity.

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