ArticleNature communications2024
HLTF disrupts Cas9-DNA post-cleavage complexes to allow DNA break processing.
Article in Nature communications, 2024. 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.
The trial behind it
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.
- Distinct repair outcomes from single and convergent replication fork collapse.Nature structural & molecular biology · 2026Article
- Rap1-mediated steric hindrance protects telomeres from MRX sensing.Nature structural & molecular biology · 2026Article
- A mutational scar-based genome-wide map of DNA double-strand break repair.Nature communications · 2026Article
- Article
- The application of CRISPR gene-editing technology in influenza prevention and control.Frontiers in genome editing · 2026Review
- The Potential of NGTs to Overcome Constraints in Plant Breeding and Their Regulatory Implications.International journal of molecular sciences · 2025Review
- Mechanism of trinucleotide repeat expansion by MutSβ-MutLγ and contraction by FAN1.Nature communications · 2025Article
- Rapid CRISPR-Cas9 target-strand nicking can provide phage resistance by reducing DNA abundance.Nucleic acids research · 2025Article
- Mechanisms and regulation of DNA end resection in the maintenance of genome stability.Nature reviews. Molecular cell biology · 2025Review
- Visualization of a multi-turnover Cas9 after product release.Nature communications · 2025Article
- High-Fidelity, One-Pot Nucleic Acid Amplification via OMEGA IsrB Nickase Cycling for Clinical Pathogen Detection.JACS Au · 2025Article
- Senataxin and DNA-PKcs redundantly promote non-homologous end joining repair of DNA double strand breaks during V(D)J recombination.Science advances · 2025Article
- Selective targeting of genome amplifications and repeat elements by CRISPR-Cas9 nickases to promote cancer cell death.Nature communications · 2025Article
- Transgene Mapping in Animals: What to Choose?International journal of molecular sciences · 2025Review
- MRN-CtIP, EXO1, and DNA2-WRN/BLM act bidirectionally to process DNA gaps in PARPi-treated cells without strand cleavage.Genes & development · 2025Article
- Post-cleavage target residence determines asymmetry in non-homologous end joining of Cas12a-induced DNA double strand breaks.Genome biology · 2025Article
- Review
- Mechanisms and regulation of replication fork reversal.DNA repair · 2024Review
- HLTF resolves G4s and promotes G4-induced replication fork slowing to maintain genome stability.Molecular cell · 2024Article
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
The outcome of CRISPR-Cas-mediated genome modifications is dependent on DNA double-strand break (DSB) processing and repair pathway choice. Homology-directed repair (HDR) of protein-blocked DSBs requires DNA end resection that is initiated by the endonuclease activity of the MRE11 complex. Using reconstituted reactions, we show that Cas9 breaks are unexpectedly not directly resectable by the MRE11 complex. In contrast, breaks catalyzed by Cas12a are readily processed. Cas9, unlike Cas12a, bridges the broken ends, preventing DSB detection and processing by MRE11. We demonstrate that Cas9 must be dislocated after DNA cleavage to allow DNA end resection and repair. Using single molecule and bulk biochemical assays, we next find that the HLTF translocase directly removes Cas9 from broken ends, which allows DSB processing by DNA end resection or non-homologous end-joining machineries. Mechanistically, the activity of HLTF requires its HIRAN domain and the release of the 3'-end generated by the cleavage of the non-target DNA strand by the Cas9 RuvC domain. Consequently, HLTF removes the H840A but not the D10A Cas9 nickase. The removal of Cas9 H840A by HLTF explains the different cellular impact of the two Cas9 nickase variants in human cells, with potential implications for gene editing.
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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.