2021-01-312021-01-312014-05-211932-62031932-6203http://dx.doi.org/10.34944/dspace/528724847939 (pubmed)http://hdl.handle.net/20.500.12613/5305Transcription 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.e98304-e98304enCC BYhttp://creativecommons.org/licenses/by/4.0/AstrocytesBrainCell NucleusCells, CulturedGene Expression Regulation, ViralHIV InfectionsHIV Long Terminal RepeatHIV-1HumansLeukocytes, MononuclearMutationPromoter Regions, GeneticRad51 RecombinaseRecombination, GeneticTranscription Factor RelATranscriptional ActivationArticle2021-01-31