Elizabeth Burke

Topic

Defining the Role of Sgs1 SUMOylation in DNA Double-Strand Break Repair

School of Molecular Life Sciences

Date & location

• Friday, September 11, 2026
• 1:00 P.M.
• Clearihue Building, Room B007

Examining Committee

Supervisory Committee

• Dr. Jennifer Cobb, School of Molecular Life Sciences, University of Victoria (Supervisor)
• Dr. Christopher Nelson, School of Molecular Life Sciences, UVic (Member)
• Dr. Nicole Templeman, Department of Biology, UVic (Outside Member)

External Examiner

• Dr. Peter Stirling, Department of Medical Genetics, University of British Columbia

Chair of Oral Examination

• Dr. Steve Perlman, Department of Biology, UVic

Abstract

DNA double-strand breaks (DSBs) are one of the most severe forms of DNA damage, and accurate repair of these breaks is essential for genome stability. The cellular response to DNA damage is coordinated by post-translational modifications like SUMOylation on numerous DNA repair factors, including the conserved RecQ helicase family. Previous work has shown that the RecQ helicase Sgs1, the budding yeast homolog of the human Bloom syndrome helicase, is SUMOylated in response to DNA damage; however, the mechanism by which this modification affects Sgs1’s function in DNA repair remains unclear. Here I show that in a SUMO-deficient Sgs1 mutant (sgs1-3KR), SUMOylation is required to retain Sgs1 association at DSBs, whereas long-range resection and homologous recombination remain largely intact, likely owing to redundancy with the Exo1 nuclease. Notably, in conditions where homologous recombination cannot be completed, this retention appears to mediate association of end-joining factors and the recruitment of Slx8 to the DSB, maintaining a local environment that is conducive to repair. Additionally, sgs1-3KR slx5Δ mutants do not phenocopy the synthetic lethality of sgs1Δ slx5Δ, identifying sgs1-3KR as a separation-of-function allele. In line with this, relocation of persistent DSBs to the nuclear periphery, and its association with the repair sites Mps3 and the nuclear pore complex, occurred independently of Sgs1 SUMOylation. Unlike the SUMO ligase-dead mutant mms21-11, neither loss of Sgs1 SUMOylation nor loss of Slx5/8 significantly shifted repair toward mutagenic alternative end joining. Together, these findings identify a novel role for Sgs1 SUMOylation in mediating productive end-joining at DSBs and refine our understanding of how Sgs1 SUMOylation contributes to the local DSB environment to facilitate DNA repair.