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DNA minicircles clarify the specific role of DNA structure on retroviral integration

dc.contributor.authorPASI, Marc
dc.contributor.authorMORNICO, Damien
dc.contributor.authorVOLANT, Stevenn
dc.contributor.authorJUCHET, Anna
dc.contributor.authorBATISSE, Julien
dc.contributor.authorBOUCHIER, Christiane
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorPARISSI, Vincent
dc.contributor.authorRUFF, Marc
dc.contributor.authorLAVERY, Richard
dc.contributor.authorLAVIGNE, Marc
dc.date.accessioned2023-07-04T13:12:12Z
dc.date.available2023-07-04T13:12:12Z
dc.date.issued2016-09-19
dc.identifier.issn0305-1048
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/183275
dc.description.abstractEnChromatin regulates the selectivity of retroviral integration into the genome of infected cells. At the nucleosome level, both histones and DNA structure are involved in this regulation. We propose a strategy that allows to specifically study a single factor: the DNA distortion induced by the nucleosome. This strategy relies on mimicking this distortion using DNA minicircles (MCs) having a fixed rotational orientation of DNA curvature, coupled with atomic-resolution modeling. Contrasting MCs with linear DNA fragments having identical sequences enabled us to analyze the impact of DNA distortion on the efficiency and selectivity of integration. We observed a global enhancement of HIV-1 integration in MCs and an enrichment of integration sites in the outward-facing DNA major grooves. Both of these changes are favored by LEDGF/p75, revealing a new, histone-independent role of this integration cofactor. PFV integration is also enhanced in MCs, but is not associated with a periodic redistribution of integration sites, thus highlighting its distinct catalytic properties. MCs help to separate the roles of target DNA structure, histone modifications and integrase (IN) cofactors during retroviral integration and to reveal IN-specific regulation mechanisms.
dc.description.sponsorshipInfrastructure Française pour la Biologie Structurale Intégrée - ANR-10-INBS-0005
dc.description.sponsorshipOrganisation et montée en puissance d'une Infrastructure Nationale de Génomique - ANR-10-INBS-0009
dc.language.isoen
dc.publisherOxford University Press
dc.rights.urihttp://creativecommons.org/licenses/by-nc/
dc.title.enDNA minicircles clarify the specific role of DNA structure on retroviral integration
dc.typeArticle de revueen_US
dc.identifier.doi10.1093/nar/gkw651
dc.subject.halSciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biochimie [q-bio.BM]
dc.subject.halSciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biologie structurale [q-bio.BM]
bordeaux.page7830 - 7847
bordeaux.volume44
bordeaux.hal.laboratoriesMFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234en_US
bordeaux.issue16
bordeaux.institutionCNRS
bordeaux.peerReviewedoui
bordeaux.import.sourcehal
hal.identifierpasteur-01416869
hal.version1
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcehal
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