ArticleJournal of virology2000
An adeno-associated virus (AAV) initiator protein, Rep78, catalyzes the cleavage and ligation of single-stranded AAV ori DNA.
Article in Journal of virology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 70 citations in OpenAlex.
- Transforming Duchenne muscular dystrophy therapy: The multifaceted role of extracellular vesicles and exosomes.Biochemistry and biophysics reports · 2026Review
- Improved Recombinant Adeno-Associated Viral Vector Production via Molecular Evolution of the Viral Rep Protein.International journal of molecular sciences · 2025Article
- European Hedgehogs as Hosts of Chaphamaparvovirus, Italy.Animals : an open access journal from MDPI · 2024Article
- Inducible HEK293 AAV packaging cell lines expressing Rep proteins.Molecular therapy. Methods & clinical development · 2023Article
- Mechanistic modeling explains the production dynamics of recombinant adeno-associated virus with the baculovirus expression vector system.Molecular therapy. Methods & clinical development · 2023Article
- Ewing sarcoma treatment: a gene therapy approach.Cancer gene therapy · 2023Review
- The adeno-associated virus 2 genome and Rep 68/78 proteins interact with cellular sites of DNA damage.Human molecular genetics · 2022Article
- Molecular detection and characterization of Carnivore chaphamaparvovirus 1 in dogs.Veterinary microbiology · 2020Article
- Evolution of dependoparvoviruses across geological timescales-implications for design of AAV-based gene therapy vectors.Virus evolution · 2020Article
- Exchange of functional domains between a bacterial conjugative relaxase and the integrase of the human adeno-associated virus.PloS one · 2018Article
- Novel Mutant AAV2 Rep Proteins Support AAV2 Replication without Blocking HSV-1 Helpervirus Replication.PloS one · 2017Article
- Germline viral "fossils" guide in silico reconstruction of a mid-Cenozoic era marsupial adeno-associated virus.Scientific reports · 2016Article
- AAV2 X increases AAV6 rep/cap-driven rAAV production.Virology · 2015Article
- Adeno-associated virus Rep represses the human integration site promoter by two pathways that are similar to those required for the regulation of the viral p5 promoter.Journal of virology · 2014Article
- Article
- Large-scale recombinant adeno-associated virus production.Human molecular genetics · 2011Review
- Adeno-associated virus: a key to the human genome?Future virology · 2010Article
- Inhibition of herpes simplex virus type 1 replication by adeno-associated virus rep proteins depends on their combined DNA-binding and ATPase/helicase activities.Journal of virology · 2010Article
- Stimulation of homology-directed gene targeting at an endogenous human locus by a nicking endonuclease.Nucleic acids research · 2009Article
- Site-specific integration of adeno-associated virus involves partial duplication of the target locus.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The Rep78 protein of adeno-associated virus (AAV) contains amino acid sequence motifs common to rolling-circle replication (RCR) initiator proteins. In this report, we describe RCR initiator-like activities of Rep78. We demonstrate that a maltose-binding protein (MBP)-Rep78 fusion protein can catalyze the cleavage and ligation of single-stranded DNA substrates derived from the AAV origin of replication. Rep-mediated single-stranded DNA cleavage was strictly dependent on the presence of certain divalent cations (e.g., Mn(2+) or Mg(2+)) but did not require the presence of a nucleoside triphosphate cofactor. Electrophoretic mobility shift assays demonstrated that binding of single-stranded DNA by MBP-Rep78 was influenced by the length of the substrate as well as the presence of potential single-stranded cis-acting sequence elements. Site-directed mutagenesis was used to examine the role of specific tyrosine residues within a conserved RCR motif (motif 3) of Rep78. Replacement of Tyr-156 with phenylalanine abolished the ability of MBP-Rep78 to mediate the cleavage and ligation of single-stranded DNA substrates but not the ability to stably bind single-stranded DNA. The cleaving-joining activity of Rep78 is consistent with the mechanism of replicative intermediate dimer resolution proposed for the autonomous parvoviruses and may have implications for targeted integration of recombinant AAV vectors.
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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.