ArticleNucleic acids research2012
Non-specific protein-DNA interactions control I-CreI target binding and cleavage.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Gene Therapy Tools for Diseases Caused by Mutations of the Mitochondrial Genome.International journal of molecular sciences · 2026Review
- Advances in gene therapy for mitochondrial genetic disorders: current status and clinical implementation challenges.Journal of translational medicine · 2025Review
- Efficient elimination of MELAS-associated m.3243G mutant mitochondrial DNA by an engineered mitoARCUS nuclease.Nature metabolism · 2023Article
- Active site residue identity regulates cleavage preference of LAGLIDADG homing endonucleases.Nucleic acids research · 2018Article
- Understanding the indirect DNA read-out specificity of I-CreI Meganuclease.Scientific reports · 2018Article
- Structure and dynamics of mesophilic variants from the homing endonuclease I-DmoI.Journal of computer-aided molecular design · 2017Article
- Applications of Alternative Nucleases in the Age of CRISPR/Cas9.International journal of molecular sciences · 2017Review
- Crystal Structure of the Homing Endonuclease I-CvuI Provides a New Template for Genome Modification.The Journal of biological chemistry · 2015Article
- Engineering of customized meganucleases via in vitro compartmentalization and in cellulo optimization.Methods in molecular biology (Clifton, N.J.) · 2015Article
- Massively parallel determination and modeling of endonuclease substrate specificity.Nucleic acids research · 2014Article
- BuD, a helix-loop-helix DNA-binding domain for genome modification.Acta crystallographica. Section D, Biological crystallography · 2014Article
- Efficient design of meganucleases using a machine learning approach.BMC bioinformatics · 2014Article
- Redesign of extensive protein-DNA interfaces of meganucleases using iterative cycles of in vitro compartmentalization.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Reprogramming homing endonuclease specificity through computational design and directed evolution.Nucleic acids research · 2014Article
- Structure of the AvrBs3-DNA complex provides new insights into the initial thymine-recognition mechanism.Acta crystallographica. Section D, Biological crystallography · 2013Article
- 5'-Cytosine-phosphoguanine (CpG) methylation impacts the activity of natural and engineered meganucleases.The Journal of biological chemistry · 2012Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Homing endonucleases represent protein scaffolds that provide powerful tools for genome manipulation, as these enzymes possess a very low frequency of DNA cleavage in eukaryotic genomes due to their high specificity. The basis of protein-DNA recognition must be understood to generate tailored enzymes that target the DNA at sites of interest. Protein-DNA interaction engineering of homing endonucleases has demonstrated the potential of these approaches to create new specific instruments to target genes for inactivation or repair. Protein-DNA interface studies have been focused mostly on specific contacts between amino acid side chains and bases to redesign the binding interface. However, it has been shown that 4 bp in the central DNA sequence of the 22-bp substrate of a homing endonuclease (I-CreI), which do not show specific protein-DNA interactions, is not devoid of content information. Here, we analyze the mechanism of target discrimination in this substrate region by the I-CreI protein, determining how it can occur independently of the specific protein-DNA interactions. Our data suggest the important role of indirect readout in this substrate region, opening the possibility for a fully rational search of new target sequences, thus improving the development of redesigned enzymes for therapeutic and biotechnological applications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.