ArticleNucleic acids research2012
Concerted nicking of donor and chromosomal acceptor DNA promotes homology-directed gene targeting in human cells.
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 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Role of complementary-sense genes and intergenic region of beet curly top virus in intermolecular recombination frequency upon local infection in plants.Journal of virology · 2025Article
- Progress and harmonization of gene editing to treat human diseases: Proceeding of COST Action CA21113 GenE-HumDi.Molecular therapy. Nucleic acids · 2023Review
- Inducing multiple nicks promotes interhomolog homologous recombination to correct heterozygous mutations in somatic cells.Nature communications · 2023Article
- Precise homology-directed installation of large genomic edits in human cells with cleaving and nicking high-specificity Cas9 variants.Nucleic acids research · 2023Article
- CRISPR-based genome editing through the lens of DNA repair.Molecular cell · 2022Review
- Review
- Review
- Efficiency and Specificity of Targeted Integration Mediated by the Adeno-Associated Virus Serotype 2 Rep 78 Protein.Human gene therapy methods · 2018Article
- In trans paired nicking triggers seamless genome editing without double-stranded DNA cutting.Nature communications · 2017Article
- Bridge-Induced Translocation betweenFrontiers in oncology · 2017Article
- Homology-directed repair of DNA nicks via pathways distinct from canonical double-strand break repair.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Genetic glycoengineering in mammalian cells.The Journal of biological chemistryReview
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The exchange of genetic information between donor and acceptor DNA molecules by homologous recombination (HR) depends on the cleavage of phosphodiester bonds. Although double-stranded and single-stranded DNA breaks (SSBs) have both been invoked as triggers of HR, until very recently the focus has been primarily on the former type of DNA lesions mainly due to the paucity of SSB-based recombination models. Here, to investigate the role of nicked DNA molecules as HR-initiating substrates in human somatic cells, we devised a homology-directed gene targeting system based on exogenous donor and chromosomal target DNA containing recognition sequences for the adeno-associated virus sequence- and strand-specific endonucleases Rep78 and Rep68. We found that HR is greatly fostered if a SSB is not only introduced in the chromosomal acceptor but also in the donor DNA template. Our data are consistent with HR models postulating the occurrence of SSBs or single-stranded gaps in both donor and acceptor molecules during the genetic exchange process. These findings can guide the development of improved HR-based genome editing strategies in which sequence- and strand-specific endonucleolytic cleavage of the chromosomal target site is combined with that of the targeting vector.
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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.