The Recruitment of the Transcription Factor YY1 to DNA Damage Sites in Human Cells

• Other Authors: Tesfazghi, Merih Tewelde (authoraut)
• Format: Others
• Language: English; English
• Published: Florida State University
• Subjects: Medicine
• Online Access: http://purl.flvc.org/fsu/fd/FSU_2016SP_Tesfazghi_fsu_0071E_13160

Our DNA is under continuous stress by endogenous and exogenous attacks such as genotoxic chemicals, ionizing radiation, and metabolic products. DNA damage is extremely detrimental, even a single unrepaired damage is sufficient to kill a cell. Cells mobilize a tightly-regulated complex repair signaling pathways to either repair or remove the damaged DNA and avoid harmful consequences such as genome instability syndromes and malignant transformations. Here, we show the rapid and transient recruitment of the transcription factor YY1 to laser-induced damage sites in living human cells in real time, suggesting an early and direct role of YY1 in DNA repair. Use of a panel of YY1 deletion constructs reveal that part of the C-terminus of the protein is required for the YY1 damage response and is the repair response domain. The recruitment of YY1 to DNA damage sites is not regulated by ATM or PARP1. However, in ATR hypomorphic cells, YY1`s retention at the damage sites was prolonged, suggesting YY1 might be directly or indirectly regulated by ATR. We also show experimentally that the transcription factor YY1 is dispensable for the recruitment of a number of major repair proteins. Overall, our findings provide evidence for early recruitment and point to important role for YY1, whether direct or indirect, in DNA repair. Future research will focus on the role of YY1 at DNA damage sites and will further our understanding in the role of YY1 in genome integrity and maintenance. === A Dissertation submitted to the Department of Biomedical Sciences in partial fulfillment of the Doctor of Philosophy. === Spring Semester 2016. === April 5, 2016. === DNA repair, Laser, Live imaging, Recruitment, Transcription factor, YY1 === Includes bibliographical references. === Myra M. Hurt, Professor Directing Dissertation; Hank Bass, University Representative; Akash Gunjan, Committee Member; Cathy Levenson, Committee Member; Yanchang Wang, Committee Member.