Yi ShengDaniel Filipe Cruz Martinho2025-04-102025-04-102023-11-142025-04-10https://hdl.handle.net/10315/42701The ubiquitin E3 ligase HUWE1 (HECT, UBA, and WWE containing protein 1) plays a crucial role in various cellular processes including DNA damage repair and has been implicated in ovarian cancer. This study therefore used cell-based assays to characterize the impact of HUWE1 depletion on DNA damage repair outcomes in response to different stressors. Since combinations of DNA-damaging agents with poly(ADP-ribose) polymerase inhibitors are being explored to improve ovarian cancer treatment, the impact of HUWE1 on DNA damage and survival following these combination treatments was also investigated. It was demonstrated that HUWE1 depletion increased cellular DNA damage and delayed DNA repair in response to treatment with various DNA damaging agents. HUWE1 depletion increased the synergistic effect of combination treatments with poly(ADP-ribose) polymerase inhibitors and DNA damaging agents on DNA damage and cell survival. The WWE domain of HUWE1 is known to interact with poly(ADP-ribose), so a potential interaction between HUWE1 and the important DNA repair protein poly(ADP-ribose) polymerase 1 was studied as a possible mechanism underlying the effects on DNA damage and cell survival. This study identified that HUWE1 is an important regulator of multiple DNA repair pathways, and a modulator of cell responsiveness to treatments with poly(ADP-ribose) polymerase inhibitors and DNA damaging agents. This suggests that HUWE1 is a possible target for improving ovarian cancer therapies.Author owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.Electronic Thesis or Dissertation2025-04-10HUWE1E3 ligaseubiquitin ligaseDNA damagePARP1PARP inhibitorPARPiPARPi combinationDNA damage and PARPicancerovarian cancercancer treatmentcancer therapy