Graduation Year
2020
Document Type
Thesis
Degree
M.S.
Degree Name
Master of Science (M.S.)
Degree Granting Department
Biology (Cell Biology, Microbiology, Molecular Biology)
Major Professor
Younghoon Kee, Ph.D.
Committee Member
Kristina Schmidt, Ph.D.
Committee Member
Huzefa Dungrawala, Ph.D.
Keywords
Transcription, DNA Damage, Polycomb, Nucleoporins
Abstract
Proliferating cells are constantly threatened by genotoxic stressors that can potentially lead to genomic instability. Breaks in the DNA, namely double-strand breaks, are detrimental sources of damage that must be repaired to maintain genomic integrity and prevent potential tumorigenesis. Here we discuss a gene silencing mechanism flanking damaged chromatin. Gene silencing and transcriptional repression at damaged DNA are necessary to prevent potential genomic aberrations from occurring through conflicts with the DNA repair machinery. BMI1, a core polycomb protein in the polycomb repressive complex 1 (PRC1) has been known to play a role in gene silencing at damaged chromatin. However, the function of BMI1 in transcriptional repression at damaged DNA in coordination with other PRC1 members remains to be fully understood. We first investigate the role PHC2, a member of PRC1 and binding partner of BMI1, in maintaining transcriptional repression at DNA damage in a concerted effort with BMI1 in the PRC1. We show that PHC2 is also essential along with BMI1 for maintenance of gene repression flanking damaged chromatin. Furthermore, our data indicates a transcriptional repression mechanism dependent on PHC2 and polycomb body formation in response to damage. Secondly, we investigate the role of nuclear pore proteins in gene silencing at double-strand breaks to elucidate double-strand break peripheral nuclear localization in human cells. We show that specific nuclear pore proteins contribute to transcriptional repression at double-strand breaks and form nuclear foci. Finally, we attempt to provide a link between PRC1 and nuclear pore proteins to understand the localization mechanism of transcriptional repression at damaged chromatin. As a result, our data demonstrates the importance in understanding how cells maintain homeostasis via gene silencing at DNA damage.
Scholar Commons Citation
DeAscanis, Dante Francis, "New Mechanisms That Regulate DNA Double-Strand Break-Induced Gene Silencing and Genome Integrity" (2020). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/9533
