ArticleNucleic acids research2022
Double-strand break toxicity is chromatin context independent.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed.
- Monitoring biological effects of somatic cell genome editing.Nature reviews. Genetics · 2026Review
- CRISPR-Cas editing technologies for viral-mediated gene therapies of human diseases: Mechanisms, progress, and challenges.Molecular therapy. Nucleic acids · 2026Review
- Article
- Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026Review
- Single-cell multiome and enhancer connectome of human retinal pigment epithelium and choroid nominate causal variants in macular degeneration.Cell reports · 2026Article
- Improved in vivo gene knockout with high specificity using multiplexed Cas12a sgRNAs.Nature communications · 2026Article
- Dissecting Gene Regulatory Networks Governing Human Cortical Cell Fate.bioRxiv : the preprint server for biology · 2025Article
- Chromatin-associated α-satellite RNA maintains chromosome stability by reestablishing SAF-A in the mitotic cell cycle.Nucleic acids research · 2025Article
- Chromatin context-dependent effects of epigenetic drugs on CRISPR-Cas9 editing.Nucleic acids research · 2024Article
- Altering traits and fates of wild populations with Mendelian DNA sequence modifying Allele Sails.Nature communications · 2024Article
- An aptamer-mediated base editing platform for simultaneous knockin and multiple gene knockout for allogeneic CAR-T cells generation.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- RAD18 directs DNA double-strand break repair by homologous recombination to post-replicative chromatin.Nucleic acids research · 2024Article
- The realization of CRISPR gene therapy.Nature chemical biology · 2024Article
- Widespread chromatin context-dependencies of DNA double-strand break repair proteins.Nature communications · 2024Article
- DNAJC9 prevents CENP-A mislocalization and chromosomal instability by maintaining the fidelity of histone supply chains.The EMBO journal · 2024Article
- Systematic characterization of the HOXA9 downstream targets in MLL-r leukemia by noncoding CRISPR screens.Nature communications · 2023Article
- Specificity of cancer-related chromosomal translocations is linked to proximity after the DNA double-strand break and subsequent selection.NAR cancer · 2023Article
- Bioinformatic and literature assessment of toxicity and allergenicity of a CRISPR-Cas9 engineered gene drive to control Anopheles gambiae the mosquito vector of human malaria.Malaria journal · 2023Article
- Phosphorylation of TRF2 promotes its interaction with TIN2 and regulates DNA damage response at telomeres.Nucleic acids research · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cells respond to double-strand breaks (DSBs) by activating DNA damage response pathways, including cell cycle arrest. We have previously shown that a single double-strand break generated via CRISPR/Cas9 is sufficient to delay cell cycle progression and compromise cell viability. However, we also found that the cellular response to DSBs can vary, independent of the number of lesions. This implies that not all DSBs are equally toxic, and raises the question if the location of a single double-strand break could influence its toxicity. To systematically investigate if DSB-location is a determinant of toxicity we performed a CRISPR/Cas9 screen targeting 6237 single sites in the human genome. Next, we developed a data-driven framework to design CRISPR/Cas9 sgRNA (crRNA) pools targeting specific chromatin features. The chromatin context was defined using ChromHMM states, Lamin-B1 DAM-iD, DNAseI hypersensitivity, and RNA-sequencing data. We computationally designed 6 distinct crRNA pools, each containing 10 crRNAs targeting the same chromatin state. We show that the toxicity of a DSB is highly similar across the different ChromHMM states. Rather, we find that the major determinants of toxicity of a sgRNA are cutting efficiency and off-target effects. Thus, chromatin features have little to no effect on the toxicity of a single CRISPR/Cas9-induced DSB.
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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 Socratic graph.