ArticleScience advances2023
PAXX binding to the NHEJ machinery explains functional redundancy with XLF.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers.
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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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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
27 citing papers in PubMed, 36 citations in OpenAlex.
- PTK7 scaffolds DNA-PKcs to promote DNA damage response and immune evasion in triple-negative breast cancer.Oncogene · 2026Article
- End processing in NHEJ by Polymerase λ and PNKP is coordinated during short-range synapsis.Nature communications · 2026Article
- DNA-PK driven nucleosome unwrapping enables NHEJ in chromatin.Nature communications · 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
- Systematic discovery of UFM1 receptors reveals a regulatory module in DNA repair directing non-homologous end-joining.Nature communications · 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
- Cryo-EM structures of NHEJ assemblies with nucleosomes.Nature communications · 2025Article
- DNA-damage dependent isoform switching modulates RIF1 DNA repair complex assembly and phase separation.The Journal of biological chemistry · 2025Article
- Oligomerisation of Ku from Mycobacterium tuberculosis promotes DNA synapsis.Nature communications · 2025Article
- 53BP1-RIF1 and DNA-PKcs show distinct genetic interactions with diverse chromosomal break repair outcomes.Nature communications · 2025Article
- Nonhomologous end-joining uses distinct mechanisms to repair each strand of a double strand break.Nature communications · 2025Article
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- Nuclear VPS35 attenuates NHEJ repair by sequestering Ku protein.Molecular medicine (Cambridge, Mass.) · 2025Article
- Structural and functional insights into the interaction between Ku70/80 and Pol X family polymerases in NHEJ.Nature communications · 2025Article
- Perspective in the Mechanisms for Repairing Sperm DNA Damage.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- DNA repair and anti-cancer mechanisms in the long-lived bowhead whale.bioRxiv : the preprint server for biology · 2024Article
- 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
- DNA-PK: A synopsis beyond synapsis.DNA repair · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
Abstract
Nonhomologous end joining is a critical mechanism that repairs DNA double-strand breaks in human cells. In this work, we address the structural and functional role of the accessory protein PAXX [paralog of x-ray repair cross-complementing protein 4 (XRCC4) and XRCC4-like factor (XLF)] in this mechanism. Here, we report high-resolution cryo-electron microscopy (cryo-EM) and x-ray crystallography structures of the PAXX C-terminal Ku-binding motif bound to Ku70/80 and cryo-EM structures of PAXX bound to two alternate DNA-dependent protein kinase (DNA-PK) end-bridging dimers, mediated by either Ku80 or XLF. We identify residues critical for the Ku70/PAXX interaction in vitro and in cells. We demonstrate that PAXX and XLF can bind simultaneously to the Ku heterodimer and act as structural bridges in alternate forms of DNA-PK dimers. Last, we show that engagement of both proteins provides a complementary advantage for DNA end synapsis and end joining in 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.