ArticleNature structural & molecular biology2018
XLF and APLF bind Ku80 at two remote sites to ensure DNA repair by non-homologous end joining.
Article in Nature structural & molecular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 102 citations in OpenAlex.
- CRISPR-mediated gap-based replacement enables site-specific DNA lesion insertion into long DNA and nucleosomes.Nucleic acids research · 2026Article
- MPP8 Facilitates DNA DSB Repair via NHEJ to Promote Chemoresistance of TNBC Independent of Methyl-H3K9 Binding.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Core NHEJ Factors Maintain Synapsis Across Diverse DNA End Structures.bioRxiv : the preprint server for biology · 2026Article
- Ku70-SAP domain has an overlapping function with DNA-PKcs in limiting the lateral movement of the Ku ring along DNA.Nucleic acids research · 2026Article
- Weak protein-bicelle binding quantification via surface-based DNA nanolevers.European biophysics journal : EBJ · 2026Article
- Structural basis of Ku-mediated activation of WRN exonuclease activity.Nature communications · 2026Article
- Nonhomologous end joining-the importance of end tethering and beyond.Genes & development · 2026Review
- Protein lactylation: a metabolic signal driving cancer therapy resistance.Cell death discovery · 2026Review
- DNA polymerase λ autoinhibition is relieved via Ku interaction during non-homologous end joining.Nucleic acids research · 2026Article
- Cryo-EM structures of NHEJ assemblies with nucleosomes.Nature communications · 2025Article
- Oligomerisation of Ku from Mycobacterium tuberculosis promotes DNA synapsis.Nature communications · 2025Article
- Training bias and sequence alignments shape protein-peptide docking by AlphaFold and related methods.Protein science : a publication of the Protein Society · 2025Article
- Restriction of Ku translocation protects telomere ends.Nature communications · 2025Article
- Article
- Structural and functional insights into the interaction between Ku70/80 and Pol X family polymerases in NHEJ.Nature communications · 2025Article
- Unveiling the mysteries of extrachromosomal circular DNA: from generation to clinical relevance in human cancers and health.Molecular cancer · 2024Review
- Multivalent interactions of the disordered regions of XLF and XRCC4 foster robust cellular NHEJ and drive the formation of ligation-boosting condensates in vitro.Nature structural & molecular biology · 2024Article
- Molecular signaling and clinical implications in the human aging-cancer cycle.Seminars in cancer biology · 2024Review
- APLF facilitates interstrand DNA crosslink repair and replication fork protection to confer cisplatin resistance.Nucleic acids research · 2024Article
- Current Strategies for Increasing Knock-In Efficiency in CRISPR/Cas9-Based Approaches.International journal of molecular sciences · 2024Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 6 institutions in 4 countries.
Funding
Abstract
The Ku70-Ku80 (Ku) heterodimer binds rapidly and tightly to the ends of DNA double-strand breaks and recruits factors of the non-homologous end-joining (NHEJ) repair pathway through molecular interactions that remain unclear. We have determined crystal structures of the Ku-binding motifs (KBM) of the NHEJ proteins APLF (A-KBM) and XLF (X-KBM) bound to a Ku-DNA complex. The two KBM motifs bind remote sites of the Ku80 α/β domain. The X-KBM occupies an internal pocket formed by an unprecedented large outward rotation of the Ku80 α/β domain. We observe independent recruitment of the APLF-interacting protein XRCC4 and of XLF to laser-irradiated sites via binding of A- and X-KBMs, respectively, to Ku80. Finally, we show that mutation of the X-KBM and A-KBM binding sites in Ku80 compromises both the efficiency and accuracy of end joining and cellular radiosensitivity. A- and X-KBMs may represent two initial anchor points to build the intricate interaction network required for NHEJ.
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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.