Affinage

LIG4

DNA ligase 4 · UniProt P49917

Length
911 aa
Mass
104.0 kDa
Annotated
2026-06-10
59 papers in source corpus 14 papers cited in narrative 15 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LIG4 encodes the ATP-dependent DNA ligase that executes the final nick-sealing step of classical non-homologous end joining (NHEJ), the dominant pathway for repairing DNA double-strand breaks and for joining coding and signal ends during V(D)J recombination (PMID:15279811, PMID:15333585, PMID:16357942). It functions as a stable complex with XRCC4, contacting XRCC4 through a coiled-coil-mediated interaction at its C-terminal domain, while XLF (Cernunnos) bridges to both partners through distinct domains to build the ligation module of the NHEJ machinery (PMID:17567543). LIG4 function depends on a defined nuclear localization signal and on its C-terminal XRCC4-binding region, both of which are required for nuclear targeting, protein stability, and activity (PMID:15333585, PMID:24027040). Hypomorphic LIG4 mutations that reduce residual ligase activity cause LIG4 syndrome (immunodeficiency and developmental delay) and a form of T-B-NK+ SCID, with residual activity scaling to clinical severity; knock-in of the R278H allele in mice recapitulates the growth retardation, lymphocyte developmental block, genomic instability and tumor predisposition (PMID:15279811, PMID:15333585, PMID:16357942, PMID:20133615). Beyond catalysis, LIG4 plays a structural scaffolding role within the NHEJ complex: catalytically inactive Lig4 partially rescues Lig4-null lethality and repair defects by maintaining the complex and permitting nuclear Lig3 to complete ligation, with loss of both being embryonic lethal (PMID:39673806). LIG4 activity is gated by multiple inputs—SMYD3-mediated methylation triggers assembly of the LIG4/XRCC4/XLF complex (PMID:38191478), PIPKIγ and lactate-bound XRCC4 each strengthen the LIG4–XRCC4 association to boost repair (PMID:40744919, PMID:41462961), and β-catenin/Wnt signaling directly transcriptionally activates LIG4 to drive radioresistance (PMID:27009971). LIG4-dependent end joining also underlies homology-independent random integration of foreign DNA (alongside POLQ) (PMID:28695890) and the ligation step of extrachromosomal circular DNA (ecDNA) biogenesis in cancer (PMID:41811450, PMID:40027615). At chromosome ends, a RAP1–TRF2 complex blocks DNA-PK from recruiting LIG4, repressing telomere fusion.

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2004 High

    Establishing LIG4 as an essential NHEJ component required showing that reduced ligase activity, rather than complete loss, underlies a human disease and scales with phenotype severity.

    Evidence Biochemical activity assays of recombinant LIG4 syndrome mutant proteins with genotype-phenotype correlation, plus mutagenesis mapping an NLS and adenylation residues

    PMID:15279811 PMID:15333585

    Open questions at the time
    • Did not resolve how partial activity loss differentially affects V(D)J versus general DSB repair
    • Structural basis of how mutations impair the enzyme not defined
  2. 2005 Medium

    Directly tying LIG4 to V(D)J recombination clarified the immunodeficiency mechanism, showing that delayed ligation permits aberrant exonucleolytic processing of recombination junctions.

    Evidence Molecular analysis of D(H)-J(H) junctions and radiosensitivity in patient cells carrying a distinct LIG4 mutation causing T-B-NK+ SCID

    PMID:16357942

    Open questions at the time
    • Single patient case
    • Did not establish the kinetic step at which ligation is rate-limiting
  3. 2007 Medium

    Defining the protein architecture of the ligation complex answered how LIG4 is organized with its partners during end joining.

    Evidence Yeast two-hybrid and reciprocal co-precipitation with domain mapping of LIG4(Dnl4)-XRCC4(Lif1) and XLF interactions

    PMID:17567543

    Open questions at the time
    • Interactions characterized largely in yeast orthologs
    • Stoichiometry and higher-order filament assembly not resolved here
  4. 2010 High

    An in vivo model was needed to confirm that the human R278H hypomorph causally produces the LIG4 syndrome phenotype.

    Evidence Lig4 R278H knock-in mice analyzed by flow cytometry, irradiation sensitivity, and tumor scoring

    PMID:20133615

    Open questions at the time
    • Does not separate developmental from repair-specific contributions
    • Mechanism of thymic tumor predisposition not dissected
  5. 2016 High

    Identifying LIG4 as a direct β-catenin target explained how an oncogenic signaling pathway controls DSB repair capacity and radioresistance.

    Evidence β-catenin ChIP, LIG4 promoter reporters, NHEJ reporter and clonogenic survival assays with knockdown/overexpression, and a conditional mouse model

    PMID:27009971

    Open questions at the time
    • Other transcriptional inputs to LIG4 not mapped
    • Did not address whether Wnt regulates LIG4 protein turnover
  6. 2017 High

    Defining the homology-independent integration routes established LIG4/NHEJ and POLQ as the two pathways mediating random foreign-DNA insertion.

    Evidence CRISPR/Cas9 LIG4/POLQ double-knockout human cells with quantitative integration assays demonstrating epistasis

    PMID:28695890

    Open questions at the time
    • Does not detail junction architecture of LIG4-mediated integrants
    • Relative contribution in primary cells unaddressed
  7. 2024 Medium

    Discovery of SMYD3-mediated LIG4 methylation revealed a post-translational trigger for assembly of the ligation complex.

    Evidence Co-IP, in vitro methylation, NHEJ reporter assays, and xenograft/SMYD3-inhibitor studies in endometrial cancer cells

    PMID:38191478

    Open questions at the time
    • Methylated residues and their structural effect not mapped
    • Single lab, single cancer context
  8. 2025 High

    A catalytic-dead knock-in established that LIG4 has a structural scaffolding role distinct from its enzymatic activity, with nuclear Lig3 able to perform ligation when LIG4 is present but inactive.

    Evidence Lig4 catalytic-site point-mutant knock-in mice crossed to nuclear Lig3-deficient strain, with lymphocyte development and lethality analysis

    PMID:39673806

    Open questions at the time
    • Molecular interface enabling Lig3 substitution not defined
    • Extent of scaffolding rescue across cell types unclear
  9. 2025 High

    Showing LIG4 catalyzes ecDNA junction ligation linked NHEJ to a cancer genome-amplification mechanism and therapy adaptation.

    Evidence Genome-wide CRISPR screen, LIG4 knockouts, ecDNA junction sequencing revealing a LIG4 signature, and drug-resistance assays across Drosophila and mammalian cells

    PMID:40027615 PMID:41811450

    Open questions at the time
    • Upstream events generating the circular precursors not defined
    • Whether LIG4 ecDNA role requires the canonical XRCC4/XLF complex untested here
  10. 2025 Medium

    Identifying PIPKIγ and lactate as enhancers of the LIG4-XRCC4 interaction revealed additional regulatory inputs that tune NHEJ-driven therapy resistance.

    Evidence Co-IP, pull-down, nuclear fractionation, XRCC4 mutagenesis/docking, and NHEJ reporter and xenograft assays in breast and ovarian cancer cells

    PMID:40744919 PMID:41462961

    Open questions at the time
    • Mechanistic detail of how interaction strengthening accelerates ligation unresolved
    • Physiological versus pathological relevance of these inputs unclear
  11. 2024 High

    Structural and biochemical work explained how telomeres avoid LIG4-mediated fusion, by RAP1-TRF2 blocking DNA-PK recruitment of LIG4.

    Evidence Cryo-EM, biochemical reconstitution, and telomere fusion assays (preprint)

    Open questions at the time
    • Preprint, not peer-reviewed
    • Whether the block is overcome under pathological telomere deprotection in vivo not addressed
  12. 2025 Low

    A developmental role was probed by testing whether LIG4/NHEJ is required for in vivo cellular reprogramming.

    Evidence In vivo LIG4/KU80 knockdown with PRKDC knockout and p53-knockdown rescue in a SOX2 glia-to-neuron reprogramming assay (preprint)

    Open questions at the time
    • Preprint and LIG4 is one of several NHEJ components tested, not isolated
    • Direct requirement for LIG4 catalytic activity not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LIG4's many regulatory inputs (methylation, transcriptional control, interaction modifiers, and telomeric exclusion) are coordinated to determine when and where ligation proceeds remains unresolved.
  • No unified structural model integrating post-translational and partner-mediated regulation
  • Hierarchy among Wnt, SMYD3, PIPKIγ and lactate inputs unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 3 GO:0060090 molecular adaptor activity 2 GO:0140098 catalytic activity, acting on RNA 2 GO:0140657 ATP-dependent activity 2
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-73894 DNA Repair 3 R-HSA-168256 Immune System 2
Complex memberships
LIG4/XRCC4/XLF NHEJ ligation complex

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 Hypomorphic mutations in DNA ligase IV (LIG4) cause LIG4 syndrome; residual ligase activity correlates with severity of clinical features including immunodeficiency and developmental delay, establishing LIG4 as an essential component of DNA non-homologous end-joining (NHEJ). Biochemical analysis of recombinant mutant proteins, clinical genotype-phenotype correlation DNA repair Medium 15279811 15333585
2004 Examination of recombinant mutant LIG4 proteins from LIG4 syndrome patients showed that two linked polymorphisms reduce DNA ligase IV activity approximately 2-fold; when combined with the R278H mutation, activity is reduced to levels comparable to other LIG4 syndrome patients with immunodeficiency and developmental delay. A nuclear localization signal was also identified in LIG4, and residues required for adenylation were mapped. Recombinant mutant protein activity assays, complementation analysis, site-directed mutagenesis Human molecular genetics High 15333585
2005 A LIG4 mutation (distinct from those in LIG4 syndrome) causes T-B-NK+ SCID with a severe block in precursor B cell differentiation; residual D(H)-J(H) junctions show extensive nucleotide deletions consistent with prolonged exonuclease activity during delayed ligation, demonstrating LIG4's direct role in V(D)J recombination end-joining. Genetic analysis, PCR analysis of V(D)J junctions, radiosensitivity assays The Journal of clinical investigation Medium 16357942
2007 DNA ligase IV (LIG4/Dnl4) interacts directly with XRCC4 (Lif1 in yeast) via a stable coiled-coil-mediated interaction; XLF (Cernunnos) also interacts with both XRCC4 and LIG4, but by different protein domains (globular head of XRCC4 contacts N- and C-terminal domains of XLF/Nej1 respectively), establishing the protein interaction architecture of the NHEJ ligation complex. Yeast two-hybrid, co-precipitation assays, domain mapping DNA repair Medium 17567543
2010 Knock-in mice homozygous for the Lig4 R278H mutation recapitulate LIG4 syndrome: growth retardation, severe T and B cell developmental block, restricted lymphocyte repertoire, genomic instability, and high thymic tumor rate, confirming that reduced LIG4 activity impairs V(D)J recombination and lymphocyte development in vivo. Knock-in mouse model, flow cytometry, irradiation sensitivity assays, tumor analysis Proceedings of the National Academy of Sciences of the United States of America High 20133615
2016 LIG4 is a direct transcriptional target of β-catenin; Wnt signalling upregulates LIG4 expression, which in turn enhances NHEJ repair in colorectal cancer cells and intestinal stem cells, providing the molecular mechanism for Wnt-induced radioresistance. Blocking LIG4 sensitizes CRC cells to radiation. β-catenin ChIP, LIG4 promoter reporter assays, LIG4 knockdown/overexpression with NHEJ reporter assays and clonogenic survival, conditional mouse model Nature communications High 27009971
2017 DNA ligase IV (LIG4) is essential for NHEJ-mediated random integration of foreign DNA in human cells; dual loss of LIG4 and DNA polymerase θ (POLQ) abolishes random integration, revealing that NHEJ (via LIG4) and theta-mediated end joining are the two homology-independent integration routes. CRISPR/Cas9 double-knockout cell lines, gene targeting assays, integration frequency measurement Nature communications High 28695890
2024 SMYD3 is recruited to DNA damage sites in a PARP1-dependent manner and directly methylates LIG4; this methylation triggers sequential assembly of the LIG4/XRCC4/XLF complex, promoting NHEJ repair. SMYD3 depletion compromises NHEJ and sensitizes endometrial cancer cells to radiation. Co-immunoprecipitation, in vitro methylation assay, NHEJ reporter assays, in vivo xenograft model, SMYD3 inhibitor treatment Oncogenesis Medium 38191478
2025 LIG4 catalyzes the ligation step in ecDNA (extrachromosomal circular DNA) biogenesis in Drosophila and mammalian cells; ecDNA from patient tumors harbors junction sites with a LIG4 signature. Disrupting LIG4 impairs ecDNA production and ecDNA-mediated adaptation to chemotherapy and targeted therapies. Genome-wide CRISPR screen, LIG4 knockout cell lines, ecDNA junction sequencing, drug resistance assays, Drosophila genetic model Proceedings of the National Academy of Sciences of the United States of America High 40027615 41811450
2025 Catalytically inactive Lig4 (point mutation at catalytic site) partially rescues the embryonic lethality and DNA repair defects of Lig4-null mice, demonstrating a structural scaffolding role for Lig4 in maintaining the NHEJ repair complex independent of its catalytic activity. Nuclear Lig3 is recruited to NHEJ complexes to perform ligation in the presence (but not activity) of Lig4; mice lacking both nuclear Lig3 and catalytically inactive Lig4 are embryonic lethal. Knock-in mouse model with catalytic-site point mutation, nuclear Lig3-deficient mouse strain, genetic crosses, lymphocyte development analysis Nucleic acids research High 39673806
2025 PIPKIγ directly interacts with LIG4 and strengthens LIG4's interaction with XRCC4, facilitating LIG4 nuclear translocation and NHEJ repair efficiency, thereby promoting radioresistance in triple-negative breast cancer cells. Co-immunoprecipitation, pull-down assays, nuclear fractionation, NHEJ reporter assays, xenograft model Cell death & disease Medium 40744919
2025 Lactate directly binds XRCC4 at residues Y66, E55, and S110, strengthening the XRCC4-LIG4 association independently of protein lactylation, thereby enhancing NHEJ efficiency and chemoresistance in ovarian cancer cells. Co-immunoprecipitation, pull-down assays, site-directed mutagenesis of XRCC4, NHEJ reporter assay, molecular docking, in vivo mouse model Biomedicines Medium 41462961
2024 RAP1, when bound to TRF2, establishes interactions with KU and DNA that prevent DNA-PK from recruiting LIG4, thereby directly repressing chromosome end joining at telomeres. This was shown biochemically and by cryo-EM structural analysis. Cryo-electron microscopy, biochemical reconstitution, cell-based telomere fusion assays bioRxiv (preprint)preprint High
2013 A LIG4 mutation (p.S205LfsX29) that eliminates the nuclear localization signal functions as a null mutation, and a second mutation (p.K635RfsX10) lacking the C-terminal XRCC4-binding region also abrogates LIG4 stability and activity, demonstrating that the NLS and the XRCC4-binding C-terminal domain are each required for LIG4 function. Genetic analysis of patient mutations, functional inference from domain ablation, clinical phenotyping Human mutation Low 24027040
2025 Knockdown of LIG4 (along with KU80) abolishes SOX2-mediated in vivo glia-to-neuron reprogramming in the adult CNS, placing LIG4-dependent NHEJ as required for this reprogramming process; p53 knockdown restores reprogramming in PRKDC-deficient mice, indicating LIG4/NHEJ acts upstream of p53 in this context. In vivo knockdown in mice, PRKDC knockout, p53 knockdown rescue, neural reprogramming assay bioRxiv (preprint)preprint Low

Source papers

Stage 0 corpus · 59 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 An overview of three new disorders associated with genetic instability: LIG4 syndrome, RS-SCID and ATR-Seckel syndrome. DNA repair 144 15279811
2005 Association of amino acid substitution polymorphisms in DNA repair genes TP53, POLI, REV1 and LIG4 with lung cancer risk. International journal of cancer 137 15609317
2005 A new type of radiosensitive T-B-NK+ severe combined immunodeficiency caused by a LIG4 mutation. The Journal of clinical investigation 137 16357942
2008 A defect of LigD (human Lig4 homolog) for nonhomologous end joining significantly improves efficiency of gene-targeting in Aspergillus oryzae. Fungal genetics and biology : FG & B 119 18282727
2006 Nonhomologous chromosomal integration of foreign DNA is completely dependent on MUS-53 (human Lig4 homolog) in Neurospora. Proceedings of the National Academy of Sciences of the United States of America 104 17003123
2004 Analysis of DNA ligase IV mutations found in LIG4 syndrome patients: the impact of two linked polymorphisms. Human molecular genetics 100 15333585
2016 LIG4 mediates Wnt signalling-induced radioresistance. Nature communications 97 27009971
2010 Polymorphisms of LIG4, BTBD2, HMGA2, and RTEL1 genes involved in the double-strand break repair pathway predict glioblastoma survival. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 97 20368557
2017 Dual loss of human POLQ and LIG4 abolishes random integration. Nature communications 78 28695890
2018 Exosome-packaged miR-1246 contributes to bystander DNA damage by targeting LIG4. British journal of cancer 76 30038324
2011 Genetic variants of the nonhomologous end joining gene LIG4 and severe radiation pneumonitis in nonsmall cell lung cancer patients treated with definitive radiotherapy. Cancer 69 21717429
2007 Epstein-Barr virus-associated B-cell lymphoma in a patient with DNA ligase IV (LIG4) syndrome. American journal of medical genetics. Part A 64 17345618
1999 Mutational analysis of Escherichia coli DNA ligase identifies amino acids required for nick-ligation in vitro and for in vivo complementation of the growth of yeast cells deleted for CDC9 and LIG4. Nucleic acids research 64 10497258
2011 Efficient gene targeting in ΔCc.ku70 or ΔCc.lig4 mutants of the agaricomycete Coprinopsis cinerea. Fungal genetics and biology : FG & B 61 21704178
2008 Polymorphisms of LIG4 and XRCC4 involved in the NHEJ pathway interact to modify risk of glioma. Human mutation 55 18165945
2012 Suppression of Ku70/80 or Lig4 leads to decreased stable transformation and enhanced homologous recombination in rice. The New phytologist 54 23050791
2007 Modes of interaction among yeast Nej1, Lif1 and Dnl4 proteins and comparison to human XLF, XRCC4 and Lig4. DNA repair 44 17567543
2010 Homozygous DNA ligase IV R278H mutation in mice leads to leaky SCID and represents a model for human LIG4 syndrome. Proceedings of the National Academy of Sciences of the United States of America 41 20133615
2009 Association between total immunoglobulin E and antibody responses to naturally acquired Ascaris lumbricoides infection and polymorphisms of immune system-related LIG4, TNFSF13B and IRS2 genes. Clinical and experimental immunology 38 19604268
2010 The role of common variants of non-homologous end-joining repair genes XRCC4, LIG4 and Ku80 in thyroid cancer risk. Oncology reports 36 20811692
2014 Relevance of LIG4 gene polymorphisms with cancer susceptibility: evidence from a meta-analysis. Scientific reports 34 25314918
2001 Phenotypic analysis and virulence of Candida albicans LIG4 mutants. Infection and immunity 28 11119499
2013 Clinical spectrum of LIG4 deficiency is broadened with severe dysmaturity, primordial dwarfism, and neurological abnormalities. Human mutation 27 24027040
2020 LIG4 syndrome: clinical and molecular characterization in a Chinese cohort. Orphanet journal of rare diseases 21 32471509
2004 Lig4 and rad54 are required for repair of DNA double-strand breaks induced by P-element excision in Drosophila. Genetics 21 15545651
2017 Comparison of genome engineering using the CRISPR-Cas9 system in C. glabrata wild-type and lig4 strains. Fungal genetics and biology : FG & B 18 28822858
2017 Polymorphisms of DNA repair genes XRCC1 and LIG4 and idiopathic male infertility. Systems biology in reproductive medicine 18 28991497
2016 Two hits in one: whole genome sequencing unveils LIG4 syndrome and urofacial syndrome in a case report of a child with complex phenotype. BMC medical genetics 18 27855655
2018 Lig4-4 selectively inhibits TREK-1 and plays potent neuroprotective roles in vitro and in rat MCAO model. Neuroscience letters 15 29438799
2020 MiR-1587 Regulates DNA Damage Repair and the Radiosensitivity of CRC Cells via Targeting LIG4. Dose-response : a publication of International Hormesis Society 14 32636722
2021 Characterization of a Cohort of Patients With LIG4 Deficiency Reveals the Founder Effect of p.R278L, Unique to the Chinese Population. Frontiers in immunology 12 34630384
2002 An evaluation of the role of LIG4 in genomic instability and adaptive mutagenesis in Candida albicans. FEMS yeast research 12 12702284
2023 Autoimmunity and immunodeficiency associated with monoallelic LIG4 mutations via haploinsufficiency. The Journal of allergy and clinical immunology 11 37004747
2019 A Novel Missense LIG4 Mutation in a Patient With a Phenotype Mimicking Behçet's Disease. Journal of clinical immunology 11 30617623
2018 Eradication of LIG4-deficient glioblastoma cells by the combination of PARP inhibitor and alkylating agent. Oncotarget 11 30627327
2015 Disruption of lig4 improves gene targeting efficiency in the oleaginous fungus Mortierella alpina 1S-4. Journal of biotechnology 11 26052021
2024 SMYD3 promotes endometrial cancer through epigenetic regulation of LIG4/XRCC4/XLF complex in non-homologous end joining repair. Oncogenesis 10 38191478
2015 Association of LIG4 and XRCC4 gene polymorphisms with the risk of human glioma in a Chinese population. International journal of clinical and experimental pathology 9 25973104
2014 The impact of functional LIG4 polymorphism on platinum-based chemotherapy response and survival in non-small cell lung cancer. Medical oncology (Northwood, London, England) 8 24722796
2014 LIG4 and RAD52 DNA repair genes polymorphisms and systemic lupus erythematosus. Molecular biology reports 7 24415301
2022 Novel CRISPR/Cas9-mediated knockout of LIG4 increases efficiency of site-specific integration in Chinese hamster ovary cell line. Biotechnology letters 6 35918621
2019 Association of XRCC6 C1310G and LIG4 T9I polymorphisms of NHEJ DNA repair pathway with risk of colorectal cancer in the Polish population. Polski przeglad chirurgiczny 6 31243170
2023 Disruption of the Schizosaccharomyces japonicus lig4 Disturbs Several Cellular Processes and Leads to a Pleiotropic Phenotype. Journal of fungi (Basel, Switzerland) 4 37233261
2012 Lack of association between LIG4 gene polymorphisms and the risk of breast cancer: a HuGE review and meta-analysis. Asian Pacific journal of cancer prevention : APJCP 4 22994770
2025 Lig3-dependent rescue of mouse viability and DNA double-strand break repair by catalytically inactive Lig4. Nucleic acids research 3 39673806
2025 BRCA1-A and LIG4 complexes mediate ecDNA biogenesis and cancer drug resistance. bioRxiv : the preprint server for biology 3 40027615
2010 The LIG4 Ile658Val polymorphism does not affect the risk of cervical carcinoma. Pathology, research and practice 3 20400235
2024 Expanding the phenotypic spectrum of LIG4 pathogenic variations: neuro-histopathological description of 4 fetuses with stenosis of the aqueduct. European journal of human genetics : EJHG 2 38351293
2019 [LIG4 syndrome: a report of four cases and literature review]. Zhonghua er ke za zhi = Chinese journal of pediatrics 2 30818900
2016 [Study of the effect of LIG4 on the radiosensitivity enhancement of rectal cancer cells by curcumin]. Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery 2 28000198
2016 Increasing the efficiency of homologous recombination vector-mediated end joining repair by inhibition of Lig4 gene using siRNA in sheep embryo fibroblasts. Yi chuan = Hereditas 1 27644744
2026 BRCA1-A and LIG4 complexes mediate ecDNA biogenesis and cancer drug resistance. Proceedings of the National Academy of Sciences of the United States of America 0 41811450
2025 Novel Compound Heterozygous Mutations of LIG4 Gene in an Indian LIG4 Syndrome Patient with Severe Microcephaly: Case Report, In-silico Analysis and Systematic Review. Current pediatric reviews 0 38591195
2025 PIPKIγ promotes non-homologous end joining through LIG4 to enhance radiotherapy resistance in triple-negative breast cancer. Cell death & disease 0 40744919
2025 Lactate Enhances Non-Homologous End Joining Repair and Chemoresistance Through Facilitating XRCC4-LIG4 Complex Assembly in Ovarian Cancer. Biomedicines 0 41462961
2025 Integrated case-control and in silico analysis of DNA double-strand break repair gene variants (RAD51, XRCC2, XRCC3, XRCC4, and LIG4) for ovarian cancer susceptibility. Gene 0 41478437
2024 A Chinese Girl With LIG4 Syndrome and Hematopoietic Stem Cell Transplantation: A Rare Case Report and Review of the Literature. Clinical case reports 0 39698004
2022 [Correlation of polymorphisms of DNA double-strand break repair genes XRCC5, LIG4 and glioma]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 35773772
2020 [Knockdown the expression of ku70 and lig4 in HEK293T cells by CRISPR/Cas13 system]. Sheng wu gong cheng xue bao = Chinese journal of biotechnology 0 32748599

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