ArticleNucleic acids research2024
DNA-PKcs suppresses illegitimate chromosome rearrangements.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Enhanced γ-globin reactivation and sickle cell correction through a repressor-to-activator motif switch in theMolecular therapy. Nucleic acids · 2026Article
- DNA-PKcs inhibitor AZD7648 reveals sgRNA cross-contaminants and enhanced sensitivity of genome engineering off-target activity in HSPCs.Nucleic acids research · 2026Article
- Complex HBB gene editing outcomes revealed by a fluorescent reporter cell model.Molecular therapy. Nucleic acids · 2026Article
- Single-cell multiplex approaches deeply map ON-target CRISPR-genotoxicity and reveal its mitigation by palbociclib and long-term engraftment.Nature communications · 2026Article
- PARP1 and PARP2 are dispensable for DNA repair by microhomology-mediated end-joining at double-ended DSBs.Nucleic acids research · 2026Article
- ESR1 fusions in breast cancer: functions, mechanisms and therapeutic opportunities.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2026Review
- A nucleoskeleton network preserves genomic integrity by promoting NHEJ and restraining chromosome translocations.Nucleic acids research · 2025Article
- 53BP1-RIF1 and DNA-PKcs show distinct genetic interactions with diverse chromosomal break repair outcomes.Nature communications · 2025Article
- APOL2 Stabilizes Ku80 to Confer NHEJ-Mediated Radioresistance in Gastric Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Genome editing with the HDR-enhancing DNA-PKcs inhibitor AZD7648 causes large-scale genomic alterations.Nature biotechnology · 2025Article
- Unlocking the Therapeutic Potential of DNA-PKcs in Cancer: Comprehensive Insights into Mechanisms and Clinical Applications.Cancers · 2025Review
- The hidden risks of CRISPR/Cas: structural variations and genome integrity.Nature communications · 2025Review
- Review
- Article
- Disparate Pathways for Extrachromosomal DNA Biogenesis and Genomic DNA Repair.Cancer discovery · 2025Article
- DNA-PKcs inhibition improves sequential gene insertion of the full-lengthMolecular therapy. Nucleic acids · 2024Article
- DNA-PKcs Inhibition Improves Sequential Gene Insertion of the Full-LengthbioRxiv : the preprint server for biology · 2024Article
- ATM and 53BP1 regulate alternative end joining-mediated V(D)J recombination.Science advances · 2024Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Two DNA repair pathways, non-homologous end joining (NHEJ) and alternative end joining (A-EJ), are involved in V(D)J recombination and chromosome translocation. Previous studies reported distinct repair mechanisms for chromosome translocation, with NHEJ involved in humans and A-EJ in mice predominantly. NHEJ depends on DNA-PKcs, a critical partner in synapsis formation and downstream component activation. While DNA-PKcs inhibition promotes chromosome translocations harboring microhomologies in mice, its synonymous effect in humans is not known. We find partial DNA-PKcs inhibition in human cells leads to increased translocations and the continued involvement of a dampened NHEJ. In contrast, complete DNA-PKcs inhibition substantially increased microhomology-mediated end joining (MMEJ), thus bridging the two different translocation mechanisms between human and mice. Similar to a previous study on Ku70 deletion, DNA-PKcs deletion in G1/G0-phase mouse progenitor B cell lines, significantly impairs V(D)J recombination and generated higher rates of translocations as a consequence of dysregulated coding and signal end joining. Genetic DNA-PKcs inhibition suppresses NHEJ entirely, with repair phenotypically resembling Ku70-deficient A-EJ. In contrast, we find DNA-PKcs necessary in generating the near-exclusive MMEJ associated with Lig4 deficiency. Our study underscores DNA-PKcs in suppressing illegitimate chromosome rearrangement while also contributing to MMEJ in both species.
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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.