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dc.creatorKaminski, R
dc.creatorWollebo, HS
dc.creatorDatta, PK
dc.creatorWhite, MK
dc.creatorAmini, S
dc.creatorKhalili, K
dc.date.accessioned2021-01-31T17:09:14Z
dc.date.available2021-01-31T17:09:14Z
dc.date.issued2014-05-21
dc.identifier.issn1932-6203
dc.identifier.issn1932-6203
dc.identifier.doihttp://dx.doi.org/10.34944/dspace/5287
dc.identifier.other24847939 (pubmed)
dc.identifier.urihttp://hdl.handle.net/20.500.12613/5305
dc.description.abstractTranscription from the HIV-1 promoter is controlled by a series of ubiquitous and inducible cellular proteins with the ability to enter the nucleus and interact with the promoter. A DNA sequence spanning nucleotides -120 to -80, which supports the association of the inducible NF-κB transcription factor, has received much attention. Here we demonstrate that the interplay between Rad51, a key regulator of the homologous recombination pathway of DNA repair and whose level is induced upon HIV-1 infection, with the NF-κB pathway, augments transcription of the viral promoter. Evidently, stimulation of the NF-κB pathway by PMA and/or TSA promotes association of Rad51 with the LTR DNA sequence and that the p65 subunit of NF-κB is important for this event. Our results also demonstrate that, similar to p65, Rad51 utilizes the NF-κB pathway to position itself in the nucleus as ectopic expression of an IκB mutant impedes its nuclear appearance and transcriptional activity upon the HIV-1 LTR. Treatment of peripheral blood mononuclear cells with small molecules that inhibit Rad51 activity results in greater than 50% decrease in the HIV-1 infection of cells. These observations provide evidence for the involvement of DNA repair factors in control of HIV-1 gene activation and offer a new avenue for the development of anti-viral therapeutics that affect viral gene transcription in latently infected cells. © 2014 Kaminski et al.
dc.format.extente98304-e98304
dc.language.isoen
dc.relation.haspartPLoS ONE
dc.relation.isreferencedbyPublic Library of Science (PLoS)
dc.rightsCC BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAstrocytes
dc.subjectBrain
dc.subjectCell Nucleus
dc.subjectCells, Cultured
dc.subjectGene Expression Regulation, Viral
dc.subjectHIV Infections
dc.subjectHIV Long Terminal Repeat
dc.subjectHIV-1
dc.subjectHumans
dc.subjectLeukocytes, Mononuclear
dc.subjectMutation
dc.subjectPromoter Regions, Genetic
dc.subjectRad51 Recombinase
dc.subjectRecombination, Genetic
dc.subjectTranscription Factor RelA
dc.subjectTranscriptional Activation
dc.titleInterplay of Rad51 with NF-κB pathway stimulates expression of HIV-1
dc.typeArticle
dc.type.genreJournal Article
dc.relation.doi10.1371/journal.pone.0098304
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.date.updated2021-01-31T17:09:10Z
refterms.dateFOA2021-01-31T17:09:14Z


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