ArticleNucleic acids research2017
Structural and functional characterization of the PNKP-XRCC4-LigIV DNA repair complex.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- End processing in NHEJ by Polymerase λ and PNKP is coordinated during short-range synapsis.Nature communications · 2026Article
- Understanding single stranded DNA gaps: from formation to fate.The Biochemical journal · 2026Review
- Fructose-2,6-bisphosphate restores TDP-43 pathology-driven genome repair deficiency in motor neuron diseases.Communications biology · 2026Article
- Machine learning insights into obesity related genes XRCC4 and ARL6 in obstructive sleep apnea.Sleep & breathing = Schlaf & Atmung · 2025Article
- B-cell immunodeficiency associated with polynucleotide kinase 3'-phosphatase (PNKP) deficiency.The journal of allergy and clinical immunology. Global · 2025Article
- Histone H3 mutations and their impact on genome stability maintenance.Biochemical Society transactions · 2024Review
- Fructose-2,6-bisphosphate restores DNA repair activity of PNKP and ameliorates neurodegenerative symptoms in Huntington's disease.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Fructose-2,6-bisphosphate restores DNA repair activity of PNKP and ameliorates neurodegenerative symptoms in Huntington's disease.bioRxiv : the preprint server for biology · 2024Article
- Site-specific acetylation of polynucleotide kinase 3'-phosphatase regulates its distinct role in DNA repair pathways.Nucleic acids research · 2024Article
- Mammalian DNA ligases; roles in maintaining genome integrity.Journal of molecular biology · 2024Review
- Extracellular vesicle-packaged circBIRC6 from cancer-associated fibroblasts induce platinum resistance via SUMOylation modulation in pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2023Article
- Novobiocin blocks nucleic acid binding to Polθ and inhibits stimulation of its ATPase activity.Nucleic acids research · 2023Article
- Structure and mechanism in non-homologous end joining.DNA repair · 2023Article
- DNA damage and repair: underlying mechanisms leading to microcephaly.Frontiers in cell and developmental biology · 2023Review
- Zika Virus Induces Mitotic Catastrophe in Human Neural Progenitors by Triggering Unscheduled Mitotic Entry in the Presence of DNA Damage While Functionally Depleting Nuclear PNKP.Journal of virology · 2022Article
- DNA End Joining: G0-ing to the Core.Biomolecules · 2021Review
- PNKP is required for maintaining the integrity of progenitor cell populations in adult mice.Life science alliance · 2021Article
- X-ray scattering reveals disordered linkers and dynamic interfaces in complexes and mechanisms for DNA double-strand break repair impacting cell and cancer biology.Protein science : a publication of the Protein Society · 2021Review
- DNA repair pathways and their roles in drug resistance for lung adenocarcinoma.Molecular biology reports · 2021Review
- Function and Molecular Mechanism of the DNA Damage Response in Immunity and Cancer Immunotherapy.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Non-homologous end joining (NHEJ) repairs DNA double strand breaks in non-cycling eukaryotic cells. NHEJ relies on polynucleotide kinase/phosphatase (PNKP), which generates 5΄-phosphate/3΄-hydroxyl DNA termini that are critical for ligation by the NHEJ DNA ligase, LigIV. PNKP and LigIV require the NHEJ scaffolding protein, XRCC4. The PNKP FHA domain binds to the CK2-phosphorylated XRCC4 C-terminal tail, while LigIV uses its tandem BRCT repeats to bind the XRCC4 coiled-coil. Yet, the assembled PNKP-XRCC4-LigIV complex remains uncharacterized. Here, we report purification and characterization of a recombinant PNKP-XRCC4-LigIV complex. We show that the stable binding of PNKP in this complex requires XRCC4 phosphorylation and that only one PNKP protomer binds per XRCC4 dimer. Small angle X-ray scattering (SAXS) reveals a flexible multi-state complex that suggests that both the PNKP FHA and catalytic domains contact the XRCC4 coiled-coil and LigIV BRCT repeats. Hydrogen-deuterium exchange indicates protection of a surface on the PNKP phosphatase domain that may contact XRCC4-LigIV. A mutation on this surface (E326K) causes the hereditary neuro-developmental disorder, MCSZ. This mutation impairs PNKP recruitment to damaged DNA in human cells and provides a possible disease mechanism. Together, this work unveils multipoint contacts between PNKP and XRCC4-LigIV that regulate PNKP recruitment and activity within NHEJ.
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Registered trials
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