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dc.contributor.authorSun, Qiming
dc.contributor.authorTsurimoto, Toshiki
dc.contributor.authorJuillard, Franceline
dc.contributor.authorLi, Lin
dc.contributor.authorLi, Shijun
dc.contributor.authorVázquez, Erika De León
dc.contributor.authorChen, She
dc.contributor.authorKaye, Kenneth
dc.date.accessioned2019-10-14T16:05:04Z
dc.date.issued2014
dc.identifier.citationSun, Q., T. Tsurimoto, F. Juillard, L. Li, S. Li, E. De Leon Vazquez, S. Chen, and K. Kaye. 2014. “Kaposi’s Sarcoma-Associated Herpesvirus LANA Recruits the DNA Polymerase Clamp Loader to Mediate Efficient Replication and Virus Persistence.” Proceedings of the National Academy of Sciences 111 (32): 11816–21. doi:10.1073/pnas.1404219111.
dc.identifier.issn0027-8424
dc.identifier.issn0744-2831
dc.identifier.issn1091-6490
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41542976*
dc.description.abstractKaposi's sarcoma-associated herpesvirus (KSHV) latently infects tumor cells and persists as a multiple-copy, extrachromosomal, circular episome. To persist, the viral genome must replicate with each cell cycle. The KSHV latency-associated nuclear antigen (LANA) mediates viral DNA replication and persistence, but little is known regarding the underlying mechanisms. We find that LANA recruits replication factor C (RFC), the DNA polymerase clamp [ proliferating cell nuclear antigen (PCNA)] loader, to drive DNA replication efficiently. Mutated LANA lacking RFC interaction was deficient for LANA-mediated DNA replication and episome persistence. RFC depletion had a negative impact on LANA's ability to replicate and maintain viral DNA in cells containing artificial KSHV episomes or in infected cells, leading to loss of virus. LANA substantially increased PCNA loading onto DNA in vitro and recruited RFC and PCNA to KSHV DNA in cells. These findings suggest that PCNA loading is a rate-limiting step in DNA replication that is incompatible with viral survival. LANA enhancement of PCNA loading permits efficient virus replication and persistence, revealing a previously unidentified mechanism for KSHV latency.
dc.language.isoen_US
dc.publisherNational Academy of Sciences
dash.licenseLAA
dc.titleKaposi's sarcoma-associated herpesvirus LANA recruits the DNA polymerase clamp loader to mediate efficient replication and virus persistence
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dash.depositing.authorKaye, Kenneth M.::ebb96ad2eeece11fa3f03d3488bbf90e::600
dc.date.available2019-10-14T16:05:04Z
dash.workflow.comments1Science Serial ID 91174
dc.identifier.doi10.1073/pnas.1404219111
dash.source.volume111;32
dash.source.page11816


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