ArticleLife science alliance2022
Sumoylation of Cas9 at lysine 848 regulates protein stability and DNA binding.
Article in Life science alliance, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Adenovirus vector-mediated delivery of the CRISPR-CasRx system enables gene knockdown with suppressed collateral activity.Molecular therapy. Nucleic acids · 2026Article
- Pml loss worsens NEK1-linked ALS and Pml induction drives NEK1 degradation, precluding disease onset.The FEBS journal · 2026Article
- Screening strategy to identify Cas9 variants with higher HDR activity based on diphtheria toxin.Journal of biomedical science · 2025Article
- CRISPR antiviral inhibits neurotrophic JC polyomavirus in 2D and 3D culture models through dual-gRNA excision by SaCas9.Molecular therapy. Nucleic acids · 2025Article
- Exploring CRISPR-Cas9 HNH-Domain-Catalyzed DNA Cleavage Using Accelerated Quantum Mechanical Molecular Mechanical Free Energy Simulation.Biochemistry · 2025Article
- C19MC drives nucleolar invasion of mitochondria and meiotic nuclear division in human cancers.iScience · 2024Article
- Engineered Cas9 variants bypass Keap1-mediated degradation in human cells and enhance epigenome editing efficiency.Nucleic acids research · 2024Article
- A platform to deliver single and bi-specific Cas9/guide RNA to perturb genes in vitro and in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Eukaryotic-driven directed evolution of Cas9 nucleases.Genome biology · 2024Article
- Engineering Cas9: next generation of genomic editors.Applied microbiology and biotechnology · 2024Review
- Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CRISPR/Cas9 is a popular genome editing technology. Although widely used, little is known about how this prokaryotic system behaves in humans. An unwanted consequence of eukaryotic Cas9 expression is off-target DNA binding leading to mutagenesis. Safer clinical implementation of CRISPR/Cas9 necessitates a finer understanding of the regulatory mechanisms governing Cas9 behavior in humans. Here, we report our discovery of Cas9 sumoylation and ubiquitylation, the first post-translational modifications to be described on this enzyme. We found that the major SUMO2/3 conjugation site on Cas9 is K848, a key positively charged residue in the HNH nuclease domain that is known to interact with target DNA and contribute to off-target DNA binding. Our results suggest that Cas9 ubiquitylation leads to decreased stability via proteasomal degradation. Preventing Cas9 sumoylation through conversion of K848 into arginine or pharmacologic inhibition of cellular sumoylation enhances the enzyme's turnover and diminishes guide RNA-directed DNA binding efficacy, suggesting that sumoylation at this site regulates Cas9 stability and DNA binding. More research is needed to fully understand the implications of these modifications for Cas9 specificity.
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Registered trials
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