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Cited by 157Virus-based gene therapy researchParvovirus B19 Infection StudiesBacteriophages and microbial interactions

Factors that bind to adeno-associated virus terminal repeats

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Im, D S, Muzyczka, N·1989·Journal of Virology
DOI 10.1128/jvi.63.7.3095-3104.1989PMC PMC250866
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Abstract

We have identified and characterized a DNA-protein complex that forms with the adeno-associated virus (AAV) terminal repeats. The complex formed only if the terminal palindrome was in the covalently closed or hairpin configuration; little if any binding was detected with the open duplex form of the terminal repeat. This fact suggested that both secondary structure and primary sequence are essential elements of recognition. DNase I protection studies indicated that virtually all of the A-A' palindrome and significant portions of the B-B' and C-C' palindromes are protected. The postulated terminal resolution site of AAV also is protected. Restriction mapping of the sequences necessary for binding indicated that almost all of the terminal palindrome must be present for binding to occur. Hairpins which are similar in size and shape to the AAV termini did not exhibit competition for binding, and the complex formed only if AAV-infected extracts were used. Thus, the binding reaction is specific for AAV sequences. The viral-coded nonstructural proteins Rep78 and Rep68 comigrated with the DNA-protein complex on neutral acrylamide gels, suggesting that one or both of these proteins are components of the complex. The characteristics of the complex suggested that it has a role in AAV DNA replication.

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  • During AAV replication, the N-terminus of the large Rep proteins binds specifically to the RBE within the ITRs and cleaves the trs, which allows self-priming and induces further replication.

    “During AAV replication, the N-terminus of the large Rep proteins (Table 2 & Figure 6A) [51] bind specifically to the RBE within the ITRs and cleave the trs [52] which allows self-priming and induces further replication.”

    From Understanding Capsid Assembly and Genome Packaging for Adeno-Associated Viruses (2017) · cites this paper as [52]

    The Abstract identifies Rep78 and Rep68 as possible components of a complex that binds AAV terminal repeats, supporting the reference to the large Rep proteins. It does not locate binding in their N-terminus. The binding and cleavage clause is attached to citation [52], not the citation being audited. (LLM, conf=0.82)

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Cited by

Sorted by citations

Authors
Im, D. S., & Muzyczka, N.
Affiliations
State University of New York (US)
ORCID
Im, D S
Venue
Journal of Virology
Publisher
American Society for Microbiology
Published
1989-07
Volume
63
Issue
7
Pages
3095-3104
ISSN
  • 0022-538X (ISSN-L)
  • 1098-5514
DOI
10.1128/jvi.63.7.3095-3104.1989
PMC
PMC250866
OpenAlex
W1879335341
Cited by
157
References
1
Citations by year
2026: 1 · 2025: 2 · 2024: 1 · 2023: 3 · 2021: 4 · 2020: 1 · 2018: 2 · 2017: 1 · 2015: 4 · 2014: 3 · 2013: 4 · 2012: 1
FWCI
6.51
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Journal of Virology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Cancer Institute (5P01CA2814607)
  • National Institute of General Medical Sciences (R01GM3572302)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Health Sciences › Medicine › Infectious Diseases › Parvovirus B19 Infection Studies
  • Physical Sciences › Environmental Science › Ecology › Bacteriophages and microbial interactions
Keywords
adeno-associated virus, terminal repeats, protein-DNA complex, hairpin secondary structure, covalently closed circular DNA, Rep78, Rep68, viral nonstructural proteins, sequence-specific DNA binding
MeSH terms
Dependovirus, Base Sequence, Cell Nucleus, Deoxyribonuclease I, DNA Replication, DNA-Binding Proteins, DNA, Viral, Genes, Viral, HeLa Cells, Humans, Molecular Sequence Data, Nucleic Acid Conformation, Repetitive Sequences, Nucleic Acid, Immunoblotting, Restriction Mapping

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