Cited by 173HIV Research and TreatmentDNA and Nucleic Acid ChemistryGenomics and Chromatin Dynamics

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The influence of DNA and nucleosome structure on integration events directed by HIV integrase

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Pruss, D., Reeves, R., Bushman, F.D., Wolffe, A.P.·1994·Journal of Biological Chemistry

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Abstract

DNA copies of the human immunodeficiency virus (HIV) genome integrate nonrandomly into the chromosomal DNA of the host cell. In this report, we investigate the molecular basis of this selectivity using the virus-encoded HIV integrase to direct integration of a synthetic HIV long terminal repeat substrate into either DNA molecules of known structure or previously defined nucleosomal complexes. We find that the structure of the target greatly influences the site of integration, and, moreover, DNA curvature, flexibility, and rigidity in solution all influence the frequency of integration. Importantly, for DNA with all of these properties, the distortion of the double helix directed by association with the histone proteins promotes the integration reaction and alters the distribution of sites that are selected for integration. We suggest that both intrinsic DNA structure and the folding of DNA into chromosomal structures will exert a major influence on target site selection for integration of the viral genome.

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Authors: Pruss, D., Reeves, R., Bushman, F. D., & Wolffe, A. P.
Affiliations: National Institutes of Health (US)
ORCID: Reeves, R.
Bushman, F.D.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1994-10
Volume: 269
Issue: 40
Pages: 25031-25041
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1016/s0021-9258(17)31494-1
OpenAlex: W1569658633
Cited by: 173
References: 63
Citations by year: 2025: 2 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 6 · 2016: 3 · 2015: 7 · 2014: 8 · 2013: 2 · 2012: 2
FWCI: 2.56
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 9520 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords: HIV integrase, viral DNA integration, target site selection, nucleosome structure, DNA curvature, DNA flexibility, histone proteins, long terminal repeat, chromatin
MeSH terms: Base Sequence, DNA, DNA Nucleotidyltransferases, HIV, Molecular Sequence Data, Nucleosomes, Virus Integration, Integrases

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The influence of DNA and nucleosome structure on integration events directed by HIV integrase

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