Investigating the Role of the E3 Ubiquitin Ligase HUWE1 in DNA Repair: Implications in Cancer Therapy

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dc.contributor.advisorYi Sheng
dc.contributor.authorDaniel Filipe Cruz Martinho
dc.date.accessioned2025-04-10T10:23:33Z
dc.date.available2025-04-10T10:23:33Z
dc.date.copyright2023-11-14
dc.date.issued2025-04-10
dc.date.updated2025-04-10T10:23:33Z
dc.degree.disciplineBiology
dc.degree.levelMaster's
dc.degree.nameMSc - Master of Science
dc.description.abstractThe 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.
dc.identifier.urihttps://hdl.handle.net/10315/42701
dc.languageen
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subject.keywordsHUWE1
dc.subject.keywordsE3 ligase
dc.subject.keywordsubiquitin ligase
dc.subject.keywordsDNA damage
dc.subject.keywordsPARP1
dc.subject.keywordsPARP inhibitor
dc.subject.keywordsPARPi
dc.subject.keywordsPARPi combination
dc.subject.keywordsDNA damage and PARPi
dc.subject.keywordscancer
dc.subject.keywordsovarian cancer
dc.subject.keywordscancer treatment
dc.subject.keywordscancer therapy
dc.titleInvestigating the Role of the E3 Ubiquitin Ligase HUWE1 in DNA Repair: Implications in Cancer Therapy
dc.typeElectronic Thesis or Dissertation

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