Structure of the termini of DNA intermediates in the integration of retroviral DNA: dependence on IN function and terminal DNA sequence
Abstract
Linear retroviral DNA, the major precursor to the integrated provirus of the murine leukemia viruses, contains a mixture of two structures at its ends: some termini are full-length and blunt, and some have recessed 3' strands. A temporal study of the end structures showed that the proportion of the DNA with recessed ends increases during the course of infection, and suggests that the blunt ends are precursors to the recessed ends. We have examined the DNA structures of the ends of retroviral mutants defective in the integration (IN) function. The results show that the formation of the recessed ends requires the presence of IN. Finally, we have analyzed the structures at the ends of mutant genomes with alterations in the terminal DNA sequence. The exact position of the recessed 3' end can be recessed one, two, or four nucleotides relative to the 5' end. In all cases the position of the recessed 3' end correlates perfectly with, and thus presumably determines, the site of joining to the target DNA.
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The U5 and U3 regions contain attachment (att) sites required for integration of the reverse-transcribed RNA into the host genome.
“These U5 and U3 regions also contain the attachment (att) sites required for the integration of the reverse-transcribed RNA into the host genome (see the U5 and U3 att sites in Fig. 3; Roth et al. 1989, Kulkosky and Skalka 1994, Coffin 1997, Masuda et al. 1998).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Roth et al. 1989
During 3′ end processing, IN removes di- or trinucleotides at both the U3 and U5 att sites downstream of the conserved CA dinucleotide, generating staggered ends.
“During this 3′ end processing, IN removes the few nucleotides (di- or trinucleotides, depending upon the retrovirus) by hydrolyzing the phosphodiester bond at both the U3 and U5 att sites downstream of the phylogenetically conserved CA dinucleotide, generating staggered ends (Fujiwara and Mizuuchi 1988, Brown et al. 1989, Roth et al. 1989).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Roth et al. 1989
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Self-citation
- Authors
- Roth, M. J., Schwartzberg, P. L., & Goff, S. P.
- Affiliations
- University of Medicine and Dentistry of New Jersey (US)
- Columbia University Irving Medical Center (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1989-07
- Volume
- 58
- Issue
- 1
- Pages
- 47-54
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2095816327
- Cited by
- 263
- References
- 51
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 1 · 2016: 5 · 2015: 7 · 2014: 3 · 2013: 3 · 2012: 1
- FWCI
- 9.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA 30488)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- retroviral integration, integrase, DNA termini, murine leukemia virus, proviral DNA, integration site selection
- MeSH terms
- Animals, Base Sequence, Cell Transformation, Viral, Cells, Cultured, DNA, Viral, Leukemia Virus, Murine, Mutation, Recombination, Genetic, Structure-Activity Relationship, Mice, Rats
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