Date of Award
Summer 6-1-2026
Embargo Period
6-1-2031
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Biochemistry and Molecular Biology
College
College of Graduate Studies
First Advisor
David T. Long
Second Advisor
Jessica H. Hartman
Third Advisor
Joe R. Delaney
Fourth Advisor
Stephen A. Duncan
Fifth Advisor
John M. Wrangle
Abstract
BRD4 (bromodomain-containing protein 4) is upregulated in a number of cancers, including ovarian cancer, where its increasing expression during tumor development is associated with decreased survival, metastasis, genomic instability, and chemoresistance. BRD4 is widely known as a transcription regulator, where it binds acetylated histones and recruits transcription initiation and elongation machinery. However, we recently showed that BRD4 plays an analogous role as a scaffold in DNA repair, directly participating in the DNA damage response. Conflicts between repair processes have been shown to promote genomic instability, but little is known about BRD4’s role in coordinating their activities. Here, we explore several roles for BRD4 in the DNA damage response using a combination of in vitro, Xenopus egg extract, and cell-based assays. We describe BRD4’s therapeutic convergence with DNA-PK inhibitors as a combined repair vulnerability in ovarian cancer. We further explore concurrent displacement of BRD4 from damaged chromatin with γH2AX accumulation at double-strand breaks. Beyond its direct role in DNA repair, we describe BRD4 as a transcriptional responder to DNA damage signaling and as a mediator of cancer cachexia. These data highlight the importance of BRD4 within the DNA damage response and provide new mechanistic insight into BRD4-regulated processes. As BRD4 plays an important role in cancer progression, this work offers a foundation for new therapeutic strategies and future research to improve outcomes for cancer patients.
Recommended Citation
Disharoon, Julie A., "The Role of BRD4 in the DNA Damage Response of Cancer" (2026). MUSC Theses and Dissertations. 1137.
https://medica-musc.researchcommons.org/theses/1137
Rights
Copyright is held by the author. All rights reserved.