ArticleJournal of virology1999
Rep-mediated nicking of the adeno-associated virus origin requires two biochemical activities, DNA helicase activity and transesterification.
Article in Journal of virology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
59 citing papers in PubMed, 88 citations in OpenAlex.
- Distinct YY dinucleotide periodicity in adeno-associated virus DNA.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Rational engineering of the P5 TRS-mimic site and REP78/68 start codon yields promoter variants that improve rAAV purity while maintaining high titers.Molecular therapy. Advances · 2026Article
- Cryo-EM structure of AAV2 Rep68 bound to integration site AAVS1: insights into the mechanism of DNA melting.Nucleic acids research · 2025Article
- A robust and flexible baculovirus-insect cell system for AAV vector production with improved yield, capsid ratios and potency.Molecular therapy. Methods & clinical development · 2024Article
- Cryo-EM Structure of AAV2 Rep68 bound to integration site AAVS1: Insights into the mechanism of DNA melting.bioRxiv : the preprint server for biology · 2024Article
- Article
- Optimization strategies and advances in the research and development of AAV-based gene therapy to deliver large transgenes.Clinical and translational medicine · 2024Review
- AAV- based vector improvements unrelated to capsid protein modification.Frontiers in medicine · 2023Review
- Rational engineering of a functional CpG-free ITR for AAV gene therapy.Gene therapy · 2022Article
- RNA-Seq Transcriptome Analysis Provides Candidate Genes for Resistance toFrontiers in plant science · 2021Article
- Entirely enzymatic nanofabrication of DNA-protein conjugates.Nucleic acids research · 2017Article
- Impact of Inverted Terminal Repeat Integrity on rAAV8 Production Using the Baculovirus/Sf9 Cells System.Human gene therapy methods · 2017Article
- Short DNA Hairpins Compromise Recombinant Adeno-Associated Virus Genome Homogeneity.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- DNA Binding and Cleavage by the Human Parvovirus B19 NS1 Nuclease Domain.Biochemistry · 2016Article
- Identification of a Functionally Relevant Adeno-Associated Virus Rep68 Oligomeric Interface.Journal of virology · 2016Article
- DNA Minicircle Technology Improves Purity of Adeno-associated Viral Vector Preparations.Molecular therapy. Nucleic acids · 2016Article
- Article
- The Adeno-Associated Virus Genome Packaging Puzzle.Journal of molecular and genetic medicine : an international journal of biomedical research · 2015Article
- Adeno-associated Virus as a Mammalian DNA Vector.Microbiology spectrum · 2015Review
- Presence of a trs-Like Motif Promotes Rep-Mediated Wild-Type Adeno-Associated Virus Type 2 Integration.Journal of virology · 2015Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The single-stranded adeno-associated virus (AAV) genome is flanked by terminal hairpinned origins of DNA replication (terminal repeats [TRs]) that are nicked at the terminal resolution site (trs) by the AAV Rep protein in an ATP-dependent, site-specific manner. Here we determine the minimal trs sequence necessary for Rep cleavage, 3'-CCGGT/TG-5', and show that this 7-base core sequence is required only on the nicked strand. We also identify a potential stem-loop structure at the trs. Interestingly, Rep nicking on a TR substrate that fixes this trs stem-loop in the extruded form no longer requires ATP. This suggests that ATP-dependent Rep helicase activity is necessary to unwind the duplex trs and extrude the stem-loop structure, prior to the ATP-independent Rep transesterification reaction. The extrusion of origin stem-loop structures prior to nicking appears to be a general mechanism shared by plant and animal viruses and bacterial plasmids. In the case of AAV, this mechanism of TR nicking would provide a possible regulatory function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.