ArticleMolecular and cellular biology2004
Mutational analysis of the N-terminal DNA-binding domain of sleeping beauty transposase: critical residues for DNA binding and hyperactivity in mammalian cells.
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 158 citations in OpenAlex.
- Exploring transposable elements: new horizons in cancer diagnostics and therapeutics.Mobile DNA · 2025Review
- DNA binding and transposition activity of the Sleeping Beauty transposase: role of structural stability of the primary DNA-binding domain.Nucleic acids research · 2025Article
- Current Non-Viral-Based Strategies to Manufacture CAR-T Cells.International journal of molecular sciences · 2024Review
- A novel hyperactive variant of theMolecular therapy. Nucleic acids · 2024Article
- Assessing and engineering the IscB-ωRNA system for programmed genome editing.Nature chemical biology · 2024Article
- Mage transposon: a novel gene delivery system for mammalian cells.Nucleic acids research · 2024Article
- EGFR core fucosylation, induced by hepatitis C virus, promotes TRIM40-mediated-RIG-I ubiquitination and suppresses interferon-I antiviral defenses.Nature communications · 2024Article
- Oncogene-Driven Induction of Orthotopic Cholangiocarcinoma in Mice.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Current strategies employed in the manipulation of gene expression for clinical purposes.Journal of translational medicine · 2022Review
- ASO-Based PKM Splice-Switching Therapy Inhibits Hepatocellular Carcinoma Growth.Cancer research · 2022Article
- RASSF1A independence and early galectin-1 upregulation in PIK3CA-induced hepatocarcinogenesis: new therapeutic venues.Molecular oncology · 2022Article
- Contemporary Transposon Tools: A Review and Guide through Mechanisms and Applications ofInternational journal of molecular sciences · 2021Review
- SHANK2 is a frequently amplified oncogene with evolutionarily conserved roles in regulating Hippo signaling.Protein & cell · 2021Article
- Enhancing site-specific DNA integration by a Cas9 nuclease fused with a DNA donor-binding domain.Nucleic acids research · 2020Article
- Affinities of Terminal Inverted Repeats to DNA Binding Domain of Transposase Affect the Transposition Activity of BambooInternational journal of molecular sciences · 2019Article
- Therapeutic Efficacy of Vitamin D in Experimental c-MET-β-Catenin-Driven Hepatocellular Cancer.Gene expression · 2019Article
- Development of a Mouse Model of Prostate Cancer Using the Sleeping Beauty Transposon and Electroporation.Molecules (Basel, Switzerland) · 2018Article
- Adenovirus-Mediated Gene Delivery: Potential Applications for Gene and Cell-Based Therapies in the New Era of Personalized Medicine.Genes & diseases · 2017Article
- DNA Transposition at Work.Chemical reviews · 2016Review
- Structural Determinants of Sleeping Beauty Transposase Activity.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The N-terminal domain of the Sleeping Beauty (SB) transposase mediates transposon DNA binding, subunit multimerization, and nuclear translocation in vertebrate cells. For this report, we studied the relative contributions of 95 different residues within this multifunctional domain by large-scale mutational analysis. We found that each of four amino acids (leucine 25, arginine 36, isoleucine 42, and glycine 59) contributes to DNA binding in the context of the N-terminal 123 amino acids of SB transposase, as indicated by electrophoretic mobility shift analysis, and to functional activity of the full-length transposase, as determined by a quantitative HeLa cell-based transposition assay. Moreover, we show that amino acid substitutions within either the putative oligomerization domain (L11A, L18A, L25A, and L32A) or the nuclear localization signal (K104A and R105A) severely impair its ability to mediate DNA transposition in mammalian cells. In contrast, each of 10 single amino acid changes within the bipartite DNA-binding domain is shown to greatly enhance SB's transpositional activity in mammalian cells. These hyperactive mutations functioned synergistically when combined and are shown to significantly improve transposase affinity for transposon end sequences. Finally, we show that enhanced DNA-binding activity results in improved cleavage kinetics, increased SB element mobilization from host cell chromosomes, and dramatically improved gene transfer capabilities of SB in vivo in mice. These studies provide important insights into vertebrate transposon biology and indicate that Sleeping Beauty can be readily improved for enhanced genetic research applications in mammals.
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