NDLI: The recombination signals for adeno-associated virus site-specific integration.

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The recombination signals for adeno-associated virus site-specific integration.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Winocour, E. Linden, R. M. Berns, K. I.
Description	Author Affiliation: Linden RM ( Department of Microbiology, Hearst Microbiology Research Center, Cornell University Medical College, NY 10021, USA.);
Abstract	The adeno-associated virus (AAV) genome integrates site specifically into a defined region of human chromosome 19 (termed AAVS1). Using a functional assay for AAV integration into AAVS1 DNA propagated as an episome, we obtained evidence that a 33-nucleotide AAVS1 DNA sequence contains the minimum signal required for targeted integration. The recombination signal comprises a DNA-binding motif for the AAV regulatory Rep protein [Rep binding site (RBS)] separated by an eight-nucleotide spacer from a sequence that can act as a substrate for Rep endonucleolytic activity [terminal resolution site (TRS)]. Mutations in either the AAVS1-encoded RBS or TRS elements abort targeted integration. Since both the RBS and TRS elements are present in the viral origin of replication and are required for AAV replication, targeted integration into chromosome 19 AAVS1 DNA may involve a replicative type of recombination that is discussed. An additional chromosome 19 element, which is responsible for DNA rearrangements in episomes propagating AAVS1 DNA, was identified and shown not to be required for AAV episomal integration, despite its location adjacent to the recombination signal.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	15
Volume Number	93
Language	English
Publisher	National Academy of Sciences
Publisher Date	1996-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Chromosomes, Human, Pair 19 Dependovirus Genetics Recombination, Genetic Virus Integration Binding Sites Cell Line DNA Helicases Metabolism DNA, Viral Chemistry DNA-Binding Proteins Genetic Vectors Genotype Models, Genetic Molecular Sequence Data Mutagenesis, Insertional Mutagenesis, Site-Directed Oligodeoxyribonucleotides Signal Transduction Trans-Activators Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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