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Structural studies of ebna1 and host telomere protection proteins at the epstein-barr virus origin of latent replication Samantha L Sustek
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Sustek, Samantha L., author.
- Language:
- English
- Subjects (All):
- Biochemistry.
- Molecular biology.
- Biophysics.
- Virology.
- 0487.
- 0307.
- 0786.
- 0720.
- Local Subjects:
- Biochemistry.
- Molecular biology.
- Biophysics.
- Virology.
- 0487.
- 0307.
- 0786.
- 0720.
- Genre:
- Academic theses
- Physical Description:
- 1 online resource (117 pages)
- Contained In:
- Dissertations Abstracts International 87-12B
- Place of Publication:
- Ann Arbor : ProQuest Dissertations and Theses, 2026
- Language Note:
- English
- Summary:
- Epstein-Barr virus (EBV) is one of the most ubiquitous human pathogens and the causative agent for an estimated 2% of human cancers. EBV persists in its host in the latent phase as circular extrachromosomal episomes and replicates exactly once per cell cycle alongside the host DNA. This process relies upon the EBV origin of replication (oriP) and the viral protein EBNA1. EBNA1 binds to oriP and, in a process that involves the host telomeric proteins TRF2 and Rap1, begins the process of DNA replication initiation using host replication machinery. In this work, we present structural and biochemical data that highlights a previously unstudied densely acidic patch on the dorsal surface of EBNA1 opposite its DNA-binding groove. We show that the acidic patch is necessary for the recruitment of TRF2 and Rap1, and for EBV replication from oriP in cell-based assays. We also present findings on the individual components of oriP: The dyad symmetry (DS) element, where recruitment of TRF2 and Rap1 occurs and where DNA replication begins, and the upstream family of repeats (FR), which is crucial for episome maintenance. Together, the data presented in this thesis shed light on how the EBV oriP contributes to viral latency, and opens up new opportunities for novel therapeutic development
- Notes:
- Source: Dissertations Abstracts International, Volume: 87-12, Section: B.
- Advisors: Lieberman, Paul M. Committee members: Gupta, Kushol; Murakami, Kenji; Black, Ben
- Ph.D. University of Pennsylvania 2026
- Vendor supplied data
- Local Notes:
- School code: 0175
- ISBN:
- 9798247973829
- Access Restriction:
- Restricted for use by site license
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