ArticleNature communications2021
Small molecule inhibition of ATM kinase increases CRISPR-Cas9 1-bp insertion frequency.
Article in Nature communications, 2021. 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, 25 citations in OpenAlex.
- SELECT: high-precision genome editing strategy via integration of CRISPR-Cas and DNA damage response for cross-species applications.Nucleic acids research · 2025Article
- CRISPR/Cas9 Ribonucleoprotein Delivery Enhanced by Lipo-Xenopeptide Carriers and Homology-Directed Repair Modulators: Insights from Reporter Cell Lines.International journal of molecular sciences · 2025Article
- Disparate Pathways for Extrachromosomal DNA Biogenesis and Genomic DNA Repair.Cancer discovery · 2025Article
- T4 DNA polymerase prevents deleterious on-target DNA damage and enhances precise CRISPR editing.The EMBO journal · 2024Article
- Dual activities of an X-family DNA polymerase regulate CRISPR-induced insertional mutagenesis across species.Nature communications · 2024Article
- Molecular Marvels: Small Molecules Paving the Way for Enhanced Gene Therapy.Pharmaceuticals (Basel, Switzerland) · 2023Review
- iMUT-seq: high-resolution DSB-induced mutation profiling reveals prevalent homologous-recombination dependent mutagenesis.Nature communications · 2023Article
- Simultaneous inhibition of DNA-PK and Polϴ improves integration efficiency and precision of genome editing.Nature communications · 2023Article
- Efficient protein tagging and cis-regulatory element engineering via precise and directional oligonucleotide-based targeted insertion in plants.The Plant cell · 2023Article
- Discovery of [1,2,3]Triazolo[4,5-ACS medicinal chemistry letters · 2023Article
- Systematic elucidation of genetic mechanisms underlying cholesterol uptake.Cell genomics · 2023Article
- Systematic elucidation of genetic mechanisms underlying cholesterol uptake.bioRxiv : the preprint server for biology · 2023Article
- High-throughput screen to identify compounds that prevent or target telomere loss in human cancer cells.NAR cancer · 2022Article
- To indel or not to indel: Factors influencing mutagenesis during chromosomal break end joining.DNA repair · 2022Review
- CRISPR-based genome editing through the lens of DNA repair.Molecular cell · 2022Review
- Predictable NHEJ Insertion and Assessment of HDR Editing Strategies in Plants.Frontiers in genome editing · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Mutational outcomes following CRISPR-Cas9-nuclease cutting in mammalian cells have recently been shown to be predictable and, in certain cases, skewed toward single genotypes. However, the ability to control these outcomes remains limited, especially for 1-bp insertions, a common and therapeutically relevant class of repair outcomes. Here, through a small molecule screen, we identify the ATM kinase inhibitor KU-60019 as a compound capable of reproducibly increasing the fraction of 1-bp insertions relative to other Cas9 repair outcomes. Small molecule or genetic ATM inhibition increases 1-bp insertion outcome fraction across three human and mouse cell lines, two Cas9 species, and dozens of target sites, although concomitantly reducing the fraction of edited alleles. Notably, KU-60019 increases the relative frequency of 1-bp insertions to over 80% of edited alleles at several native human genomic loci and improves the efficiency of correction for pathogenic 1-bp deletion variants. The ability to increase 1-bp insertion frequency adds another dimension to precise template-free Cas9-nuclease genome editing.
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Registered trials
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