ArticleNucleic acids research2016
Phosphorylation of Ku dictates DNA double-strand break (DSB) repair pathway choice in S phase.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 101 citations in OpenAlex.
- OV16 Improves Radiation-Induced Intestinal Injury by Targeting Transglutaminase 2.Molecules (Basel, Switzerland) · 2026Article
- CK2-mediated HDAC5 shuttling regulates DNA end resection through Ku70 deacetylation.Theranostics · 2026Article
- Nuclear VPS35 attenuates NHEJ repair by sequestering Ku protein.Molecular medicine (Cambridge, Mass.) · 2025Article
- Characterization of the role of spatial proximity of DNA double-strand breaks in the formation of CRISPR-Cas9-induced large structural variations.Genome research · 2025Article
- Defective homologous recombination and genomic instability predict increased responsiveness to carbon ion radiotherapy in pancreatic cancer.NPJ precision oncology · 2025Article
- Perspective in the Mechanisms for Repairing Sperm DNA Damage.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- DNA-PK: A synopsis beyond synapsis.DNA repair · 2024Review
- Identification of the main barriers to Ku accumulation in chromatin.Cell reports · 2024Article
- CircCDYL2 bolsters radiotherapy resistance in nasopharyngeal carcinoma by promoting RAD51 translation initiation for enhanced homologous recombination repair.Journal of experimental & clinical cancer research : CR · 2024Article
- Molecular cloning, subcellular localization, and rapid recruitment to DNA damage sites of chicken Ku70.Scientific reports · 2024Article
- Identification of the main barriers to Ku accumulation in chromatin.bioRxiv : the preprint server for biology · 2024Article
- Ubiquitin-proteasome pathway-mediated regulation of the Bcl-2 family: effects and therapeutic approaches.Haematologica · 2024Review
- Effects of Differing Underlying Assumptions in In Silico Models on Predictions of DNA Damage and Repair.Radiation research · 2023Article
- Structural and functional basis of inositol hexaphosphate stimulation of NHEJ through stabilization of Ku-XLF interaction.Nucleic acids research · 2023Article
- Short-range end resection requires ATAD5-mediated PCNA unloading for faithful homologous recombination.Nucleic acids research · 2023Article
- Review
- Genome-wide analysis of DNA-PK-bound MRN cleavage products supports a sequential model of DSB repair pathway choice.Nature communications · 2023Article
- Short Double-Stranded DNA (≤40-bp) Affects Repair Pathway Choice.International journal of molecular sciences · 2023Article
- LncRNA HOTAIRM1 functions in DNA double-strand break repair via its association with DNA repair and mRNA surveillance factors.Nucleic acids research · 2023Article
- CRISPR-based gene editing of non-homologous end joining factors biases DNA repair pathway choice toward single-strand annealing inCurrent research in biotechnology · 2023Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Multiple DNA double-strand break (DSB) repair pathways are active in S phase of the cell cycle; however, DSBs are primarily repaired by homologous recombination (HR) in this cell cycle phase. As the non-homologous end-joining (NHEJ) factor, Ku70/80 (Ku), is quickly recruited to DSBs in S phase, we hypothesized that an orchestrated mechanism modulates pathway choice between HR and NHEJ via displacement of the Ku heterodimer from DSBs to allow HR. Here, we provide evidence that phosphorylation at a cluster of sites in the junction of the pillar and bridge regions of Ku70 mediates the dissociation of Ku from DSBs. Mimicking phosphorylation at these sites reduces Ku's affinity for DSB ends, suggesting that phosphorylation of Ku70 induces a conformational change responsible for the dissociation of the Ku heterodimer from DNA ends. Ablating phosphorylation of Ku70 leads to the sustained retention of Ku at DSBs, resulting in a significant decrease in DNA end resection and HR, specifically in S phase. This decrease in HR is specific as these phosphorylation sites are not required for NHEJ. Our results demonstrate that the phosphorylation-mediated dissociation of Ku70/80 from DSBs frees DNA ends, allowing the initiation of HR in S phase and providing a mechanism of DSB repair pathway choice in mammalian cells.
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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.