The Epstein-Barr virus (EBV) EBNA1 protein mediates the replication and mitotic segregation of the EBV genomes via interactions with the viral oriP sequences. C666-1 is the only known nasopharyngeal carcinoma (NPC) cell line that stably maintains EBV in culture and I investigated whether this is due to differences in oriP-mediated functions in replication and segregation. I found that both C666-1 and EBV-negative NPC cell lines can replicate and maintain oriP plasmids for extended periods but that high EBNA1 levels interfered with plasmid segregation. The segregation element within oriP was recently shown to contain 29 repeated sequences instead of the 20 repeats in initial oriP isolates. I compared the functions of oriP with 20 or 29 repeats and found that the higher number of repeats decreased plasmid replication but increased plasmid maintenance, consistent with a segregation effect. Finally, I identified a potential role for promyelocytic leukemia nuclear bodies in oriP plasmid replication.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/32632 |
| Date | 16 August 2012 |
| Creators | Thawe, Natalia |
| Contributors | Frappier, Lori |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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