A bend, flip and trap mechanism for transposon integration
Open accessAbstract
Cut-and-paste DNA transposons of the mariner/Tc1 family are useful tools for genome engineering and are inserted specifically at TA target sites. A crystal structure of the mariner transposase Mos1 (derived from Drosophila mauritiana), in complex with transposon ends covalently joined to target DNA, portrays the transposition machinery after DNA integration. It reveals severe distortion of target DNA and flipping of the target adenines into extra-helical positions. Fluorescence experiments confirm dynamic base flipping in solution. Transposase residues W159, R186, F187 and K190 stabilise the target DNA distortions and are required for efficient transposon integration and transposition in vitro. Transposase recognises the flipped target adenines via base-specific interactions with backbone atoms, offering a molecular basis for TA target sequence selection. Our results will provide a template for re-designing mariner/Tc1 transposases with modified target specificities.
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Intasomes from several retroviral species and prokaryotic and eukaryotic transpososomes have been visualized as post-catalytic strand transfer complexes, all showing sharp deformations of target DNA.
“Intasomes from several retroviral species as well as prokaryotic and eukaryotic transpososomes have been visualised as post-catalytic strand transfer complexes, all of which display sharp deformations of target DNA29,30,32,33,37,51–54.”
From Structure and function of retroviral integrase (2022) · cites this paper as [53]
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- Authors
- Morris, E. R., Grey, H., McKenzie, G., Jones, A. C., & Richardson, J. M.
- Affiliations
- National Institute for Medical Research (GB)
- University of Edinburgh (GB)
- Corresponding author
- Richardson, Julia M
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2016-05-25
- Volume
- 5
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC5481204
- OpenAlex
- W2372602845
- Cited by
- 26
- References
- 46
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 4
- FWCI
- 1.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (publishedVersion, cc-by)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Durham Research Online (Durham University) (submittedVersion, cc-by)
- Funders
- Biotechnology and Biological Sciences Research Council (BJ000884)
- Wellcome Trust (085176/Z/08/Z)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- mariner transposon, Tc1 transposon, DNA integration, base flipping, target specificity, Drosophila mauritiana
- MeSH terms
- DNA, DNA Transposable Elements, DNA-Binding Proteins, Models, Molecular, Nucleic Acid Conformation, Protein Binding, Protein Conformation, Recombination, Genetic, Crystallography, X-Ray, Transposases
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