Presence of a trs-like motif promotes rep-mediated wild-type adeno-associated virus type 2 integration

High-throughput integration site (IS) analysis of wild-type adeno-associated virus type 2 (wtAAV2) in human dermal fibroblasts (HDFs) and HeLa cells revealed that juxtaposition of a Rep binding site (RBS) and terminal resolution site (trs)-like motif leads to a 4-fold-increased probability of wtAAV...

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Hauptverfasser: Petri, Karl (VerfasserIn) , Gabriel, Richard (VerfasserIn) , Fronza, Raffaele (VerfasserIn) , Afzal, Saira (VerfasserIn) , Käppel, Christine (VerfasserIn) , Schmidt, Manfred (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: July 2015
In: Journal of virology
Year: 2015, Jahrgang: 89, Heft: 14, Pages: 7428-7432
ISSN:1098-5514
DOI:10.1128/JVI.00426-15
Online-Zugang:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1128/JVI.00426-15
Verlag, kostenfrei, Volltext: https://journals.asm.org/doi/10.1128/jvi.00426-15
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Verfasserangaben:Karl Petri, Richard Gabriel, Leticia Agundez, Raffaele Fronza, Saira Afzal, Christine Kaeppel, R. Michael Linden, Els Henckaerts, Manfred Schmidt
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Zusammenfassung:High-throughput integration site (IS) analysis of wild-type adeno-associated virus type 2 (wtAAV2) in human dermal fibroblasts (HDFs) and HeLa cells revealed that juxtaposition of a Rep binding site (RBS) and terminal resolution site (trs)-like motif leads to a 4-fold-increased probability of wtAAV integration. Electrophoretic mobility shift assays (EMSAs) confirmed binding of Rep to off-target RBSs. For the first time, we show Rep protein off-target nicking activity, highlighting the importance of the nicking substrate for Rep-mediated integration.
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Beschreibung:Online Resource
ISSN:1098-5514
DOI:10.1128/JVI.00426-15