Affinage

LIG3

DNA ligase 3 · UniProt P49916

Round 2 corrected
Length
1009 aa
Mass
112.9 kDa
Annotated
2026-04-28
55 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LIG3 (DNA ligase 3) is the principal nick-sealing enzyme in base excision repair and single-strand break repair, functioning as a stable complex with XRCC1, which both stabilizes LIG3 protein levels and scaffolds multiprotein repair assemblies containing DNA polymerase β, PNK, TDP1, and NEIL1 (PMID:8264637, PMID:8532526, PMID:11163244, PMID:15260972, PMID:15744309). LIG3 encodes the sole mitochondrial DNA ligase, essential for mtDNA maintenance; biallelic loss-of-function variants cause mitochondrial neurogastrointestinal encephalomyopathy with mtDNA depletion (PMID:33855352, PMID:39173721). Beyond BER, nuclear LIG3α participates in PARP1-dependent alternative non-homologous end-joining of double-strand breaks, repairs telomere-internal DSBs, and is recruited to classical NHEJ complexes scaffolded by LIG4 when LIG4 catalytic activity is absent (PMID:27806302, PMID:39673806, PMID:24013086). LIG3α also serves as a backup Okazaki fragment ligase recruited via PARP1–HPF1-mediated ADP-ribosylation of histone H3 when LIG1 is depleted, and cooperates with YY1 in PARylation-dependent extrachromosomal DNA biogenesis (PMID:33872376, PMID:40769147).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1995 High

    Establishing that LIG3 is the dedicated ligase of base excision repair required identifying its obligate partner: copurification and in vitro reconstitution demonstrated that XRCC1 forms a direct, salt-resistant complex with LIG3 and stabilizes its protein levels in vivo, explaining why XRCC1-deficient cells are hypersensitive to DNA damage.

    Evidence Affinity chromatography copurification, far Western blotting, and quantitative Western blots in XRCC1-deficient CHO cells

    PMID:8264637 PMID:8532526

    Open questions at the time
    • Structural basis of the XRCC1–LIG3 interface not resolved at atomic level at this stage
    • Whether LIG3 functions independently of XRCC1 in any context was unknown
  2. 1996 High

    Full reconstitution of single-nucleotide BER with purified human UDG, APE, pol β, and LIG3 established LIG3 as a bona fide BER nick ligase and showed that XRCC1, while not absolutely required for ligation, channels repair toward short-patch BER by suppressing pol β strand displacement.

    Evidence In vitro BER reconstitution with purified human proteins, far Western, yeast two-hybrid domain mapping

    PMID:8978692

    Open questions at the time
    • Long-patch BER contributions of LIG3 versus LIG1 not delineated
    • In vivo redundancy between LIG1 and LIG3 in BER not yet addressed
  3. 2005 High

    Discovery that LIG3α assembles multi-protein SSBR complexes containing PNK, pol β, TDP1, and NEIL1 expanded its role from BER nick sealing to a central effector of single-strand break repair, including repair of abortive topoisomerase 1 intermediates in post-mitotic neurons.

    Evidence Co-immunoprecipitation of endogenous complexes from human cell extracts, functional SSBR assay in SCAN1 patient cells, and APE-independent BER reconstitution

    PMID:11163244 PMID:15260972 PMID:15744309

    Open questions at the time
    • Order of assembly of SSBR sub-complexes on damaged chromatin not resolved
    • Whether LIG3 directly contacts TDP1 or is bridged by XRCC1 was unclear
  4. 2013 High

    Recognition that LIG3 encodes the sole mitochondrial DNA ligase and also operates in an XRCC1-independent alternative NHEJ pathway for DSBs resolved a long-standing question about how a single gene serves three distinct repair compartments—mitochondrial replication/repair, nuclear BER/SSBR, and alt-NHEJ.

    Evidence Synthesis of functional complementation, knockdown studies, and biochemical assays across multiple systems

    PMID:24013086

    Open questions at the time
    • Regulation of isoform-specific targeting (mitochondrial vs. nuclear) not mechanistically defined
    • Relative contribution of LIG3 versus LIG1 in nuclear BER in vivo still debated
  5. 2016 Medium

    Demonstration that telomere-internal DSBs are repaired partly by PARP1- and LIG3-dependent alt-NHEJ extended LIG3's DSB repair role to a specialized chromosomal context where classical NHEJ is modulated by shelterin.

    Evidence Inducible FokI DSB system at telomeres, genetic depletion of PARP1/LIG3, Southern blot and FISH

    PMID:27806302

    Open questions at the time
    • Whether this alt-NHEJ pathway acts at natural telomere erosion events remains untested
    • Mechanism by which shelterin permits LIG3-dependent repair at internal sites is undefined
  6. 2018 Medium

    The discovery that MALAT1 lncRNA binds both PARP1 and LIG3 to stabilize the alt-NHEJ complex in myeloma suggested a non-coding RNA scaffolding mechanism for alt-NHEJ, opening a link between aberrant alt-NHEJ and cancer-cell survival.

    Evidence RNA immunoprecipitation, antisense knockdown, xenograft models

    PMID:29632340

    Open questions at the time
    • Direct binding interface between MALAT1 and LIG3 not mapped
    • Generalizability beyond multiple myeloma not established
    • Whether MALAT1 modulates LIG3 catalytic activity or only complex assembly is unclear
  7. 2021 High

    Cell-free reconstitution in Xenopus egg extracts revealed that PARP1–HPF1-dependent ADP-ribosylation of histone H3 recruits LIG3–XRCC1 to chromatin as a backup Okazaki fragment ligase when LIG1 is absent, defining a new replicative role for LIG3.

    Evidence Xenopus egg extract replication system with sequential immunodepletion and chromatin fractionation

    PMID:33872376

    Open questions at the time
    • Whether this backup pathway is physiologically engaged during normal S phase in mammalian cells is uncertain
    • Frequency of PARP1-dependent LIG3 recruitment versus LIG1-mediated ligation in vivo unknown
  8. 2021 High

    Identification of biallelic LIG3 loss-of-function variants as the cause of mitochondrial neurogastrointestinal encephalomyopathy—confirmed by reduced ligase activity in patient cells and phenocopy in zebrafish—established LIG3 as a disease gene and proved its essential mitochondrial function in vertebrates.

    Evidence Whole exome sequencing across multiple families, in vitro ligase activity assay, mtDNA copy number, zebrafish lig3 knockout

    PMID:33855352

    Open questions at the time
    • Whether nuclear repair defects contribute to the clinical phenotype is unknown
    • Genotype–phenotype correlations across different LIG3 mutation types not yet defined
  9. 2025 High

    Mouse genetics demonstrated that nuclear LIG3 is dispensable for viability but becomes essential when LIG4 catalytic activity is lost, proving that LIG3 is recruited into NHEJ complexes scaffolded by the structural (non-catalytic) role of LIG4, thus resolving an epistatic hierarchy among DNA ligases in DSB repair.

    Evidence Conditional nuclear Lig3 knockout crossed with catalytically inactive Lig4 knock-in mice; embryonic lethality analysis

    PMID:39673806

    Open questions at the time
    • Structural mechanism of LIG3 recruitment to the LIG4/XRCC4 scaffold is not resolved
    • Whether LIG3 engagement at NHEJ is regulated by post-translational modification is untested
  10. 2025 High

    Substrate-selectivity studies revealed that LIG3α can seal mutagenic dATP:8-oxoG nick products but fails on correct dCTP:8-oxoG products—a distinction not shared by LIG1—defining a unique fidelity checkpoint for LIG3 at oxidatively damaged bases, with APE1 serving as a proofreader of ligase-failure intermediates.

    Evidence In vitro nick-sealing assay with purified LIG3α, LIG1, pol β, and defined 8-oxoG substrates

    PMID:40286853

    Open questions at the time
    • In vivo mutagenic consequences of this substrate discrimination are not quantified
    • How LIG3's zinc-finger domain contributes to its selectivity on damaged nicks is structurally unresolved
  11. 2025 Medium

    A PARylation-dependent mechanism coupling YY1-mediated DNA looping to LIG3-catalyzed religation was shown to drive extrachromosomal DNA (ecDNA) biogenesis in cancer cells, extending LIG3's repertoire to a pathological genome-restructuring process suppressible by PARP inhibitors.

    Evidence Proximity ligation assay, live-cell imaging, PARP inhibitor treatment in human cancer cells

    PMID:40769147

    Open questions at the time
    • Mechanistic model is partially computational (multi-layer perceptron); direct biochemical reconstitution of the LIG3–YY1 religation step is lacking
    • Whether ecDNA biogenesis uses alt-NHEJ or a distinct LIG3-dependent mechanism is unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of LIG3 recruitment to diverse repair scaffolds (XRCC1, PARP1, LIG4/XRCC4), how isoform-specific targeting between mitochondria and nucleus is regulated post-translationally, and whether the substrate selectivity of LIG3 versus LIG1 at oxidative lesions shapes mutation spectra in vivo.
  • No high-resolution structure of full-length LIG3 in complex with XRCC1 or at a nick substrate
  • Post-translational regulation of LIG3 (acetylation, phosphorylation, PARylation) poorly characterized in vivo
  • Relative partitioning of LIG3 between BER, SSBR, alt-NHEJ, backup OFM, and ecDNA biogenesis under physiological conditions unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 8 GO:0016874 ligase activity 4 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 7 GO:0005739 mitochondrion 5 GO:0005694 chromosome 1
Pathway
R-HSA-73894 DNA Repair 11 R-HSA-1852241 Organelle biogenesis and maintenance 4 R-HSA-1643685 Disease 3 R-HSA-69306 DNA Replication 2
Partners
HPF1NEIL1PARP1PNKPOLBTDP1XRCC1YY1
Complex memberships
LIG3–YY1 ecDNA biogenesis complexPARP1–LIG3 alt-NHEJ complexXRCC1–LIG3α SSBR/BER complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 LIG3 (DNA ligase III) physically interacts with XRCC1 to form a stable complex; XRCC1 is required for normal levels of DNA ligase III activity, and XRCC1-deficient cells show ~4-6 fold reduced DNA ligase III activity, implicating LIG3 as the major DNA ligase in base excision repair. Affinity chromatography copurification, far Western blotting Molecular and cellular biology High 8264637
1995 XRCC1 directly interacts with DNA ligase III in vitro forming a salt-resistant complex (resistant to 2 M NaCl); the level of LIG3 polypeptide is reduced ~4-fold in XRCC1-deficient mutant CHO cells (EM9, EM-C11), indicating XRCC1 stabilizes LIG3 protein in vivo. In vitro binding assay with purified recombinant XRCC1-His, far Western blotting, Western blot quantification Nucleic acids research High 8532526
1996 BER was reconstituted in vitro with purified human UDG, APE, DNA polymerase beta, and DNA ligase III; XRCC1 is not absolutely required for ligation but suppresses strand displacement by pol beta, enabling more efficient single-nucleotide patch repair; XRCC1 interacts directly with pol beta at residues 84-183 (N-terminal half), while its C-terminal region binds LIG3. In vitro BER reconstitution, far Western blotting, affinity precipitation, yeast two-hybrid, gel retardation supershift The EMBO journal High 8978692
2001 LIG3α, XRCC1, DNA polymerase beta, and polynucleotide kinase (PNK) are coassociated in multiprotein complexes in human cell extracts and together repair oxidative/IR-induced single-strand breaks; XRCC1 stimulates PNK kinase and phosphatase activities at damaged DNA termini. Co-immunoprecipitation of endogenous multiprotein complexes, in vitro single-strand break repair assay Cell High 11163244
2004 LIG3α stably interacts with NEIL1 and DNA polymerase beta; together with PNK, these form an APE-independent BER complex for repair of oxidized bases producing 3'-phosphate termini. Stable interaction (co-immunoprecipitation/affinity pulldown), in vitro BER assay Molecular cell High 15260972
2005 TDP1 is sequestered into multi-protein single-strand break repair complexes via direct interaction with DNA ligase IIIα; these complexes are catalytically inactive in SCAN1 (TDP1-mutant) patient cells, implicating LIG3α in repair of chromosomal SSBs arising from abortive topoisomerase 1 activity or oxidative stress in post-mitotic neurons. Co-immunoprecipitation of endogenous complexes, in vitro SSBR assay with patient cell extracts Nature High 15744309
2013 The LIG3 gene encodes multiple polypeptides with distinct cellular functions: the only mitochondrial DNA ligase (essential for mitochondrial DNA maintenance), a nuclear form that partners with XRCC1 in BER and SSB repair, and a nuclear form that functions in an alternative NHEJ (alt-NHEJ) pathway for DSB repair independently of XRCC1. In cancer cells LIG3α is frequently overexpressed and serves as a biomarker for alt-NHEJ dependence. Review synthesizing functional complementation, in vitro assays, and knockdown studies Gene High 24013086
2015 In BCR-ABL1- and FLT3/ITD-activated leukemias, constitutive tyrosine kinase signaling activates c-MYC, which transcriptionally upregulates LIG3 and PARP1 while suppressing miR-150 and miR-22 (which inversely correlate with LIG3/PARP1 expression); this leads to elevated alt-NHEJ activity and increased genomic deletions using DNA microhomologies. qRT-PCR, Western blot, miRNA overexpression/inhibition, alt-NHEJ functional assay, c-MYC inhibition in cultured leukemia cells and primary patient samples Molecular cancer research : MCR Medium 25828893
2016 Telomere-internal DSBs (induced by FokI) are repaired partly by a PARP1- and Ligase3-dependent reaction consistent with alt-NHEJ (microhomology-mediated end-joining), in addition to homologous recombination; shelterin does not suppress ATM signaling or DSB repair at telomere-internal sites. Inducible FokI-based DSB system at telomeres, genetic depletion of PARP1/LIG3, Southern blot telomere analysis, FISH Cell reports Medium 27806302
2018 MALAT1 lncRNA binds PARP1 and LIG3, two key components of the alt-NHEJ complex, in multiple myeloma cells; degradation of MALAT1 by antisense oligonucleotides disrupts this complex, leading to poly-ADP-ribosylation of nuclear proteins, defective alt-NHEJ repair, and induction of apoptosis. RNA immunoprecipitation, antisense knockdown (RNase H gapmer oligos), SWCNT delivery in xenograft models, PARP1 inhibitor combination assay Leukemia Medium 29632340
2019 SIRT3 deacetylates LIG3 along with other mitochondrial BER proteins (NEIL1, NEIL2, OGG1, MUTYH, APE1) in mitochondria, modulating their enzymatic activity; LIG3 is identified as a substrate of SIRT3 deacetylase activity relevant to mitochondrial BER. Deacetylation assay with SIRT3, Western blot, colorectal cancer cell analysis Polski przeglad chirurgiczny Low 32312920
2021 RAD52 inhibits SSBR by binding ssDNA and poly(ADP-ribose) with high affinity, thereby reducing DNA-damage-promoted XRCC1/LIG3α co-localization at SSB sites; this inhibitory function of RAD52 on SSBR counterbalances its role in DSBR and is required for balancing cell survival versus genomic integrity. RAD52 KO cell lines, live-cell imaging of XRCC1/LIG3α foci co-localization, PAR binding assays, survival assays with CPT Cell reports Medium 33440161
2021 Using a Xenopus egg extract cell-free system, PARP1-HPF1-dependent ADP-ribosylation of histone H3 is required to recruit the LIG3-XRCC1 complex onto chromatin as a backup ligation system for Okazaki fragment joining when LIG1 is absent; depletion of PARP1 or HPF1 prevents LIG3 chromatin recruitment and causes failure of Okazaki fragment ligation in LIG1-depleted extracts. Xenopus egg extract cell-free replication system, immunodepletion, chromatin fractionation, ADP-ribosylation assay Nucleic acids research High 33872376
2021 Biallelic loss-of-function variants in LIG3 cause mitochondrial neurogastrointestinal encephalomyopathy; patient-derived cells show decreased LIG3 protein levels and reduced ligase activity, with impaired mtDNA maintenance leading to mtDNA depletion (without accumulation of multiple deletions); disruption of lig3 in zebrafish reproduces brain and gut transit phenotypes. Whole exome sequencing, in vitro ligase activity assay in patient cells, mtDNA copy number quantification, zebrafish lig3 morpholino/knockout Brain : a journal of neurology High 33855352
2024 LIG3 mutations in patients cause mitochondrial dysfunction with impaired ATP production; LIG3-mutant fibroblasts exhibit impaired mitophagy, altered Ca2+ homeostasis, and overexpression of extracellular matrix genes; l-glutamine supplementation restores ATP production and growth rate in mutant cells. Transcriptome analysis, live-cell mitochondrial function assay, immunostaining, Western blot in patient-derived fibroblasts Gastroenterology Medium 39173721
2025 LIG3α seals the nick product of pol beta mutagenic dATP insertion opposite 8-oxoG but is unable to ligate pol beta dCTP:8-oxoG insertion products (unlike LIG1 which seals both); ribonucleotide insertions by pol beta eliminate repair coordination with both LIG1 and LIG3α, and APE1 proofreads nick intermediates with 3'-mismatches or ribonucleotides templating 8-oxoG. In vitro nick-sealing ligation assay with purified proteins, gel-based BER activity assay The Journal of biological chemistry High 40286853
2025 Nuclear LIG3-deficient mice are viable and moderately smaller with elevated cerebral ventricle dilation, but mice lacking both nuclear LIG3 and catalytically inactive Lig4 are embryonic lethal, demonstrating that LIG3 is recruited to and functionally substitutes at NHEJ repair complexes assembled around the structural scaffold of Lig4. Mouse genetic crosses, conditional Lig3 nuclear knockout, catalytically inactive Lig4 knock-in, timed mating embryonic lethality analysis Nucleic acids research High 39673806
2025 ecDNA biogenesis depends on YY1-mediated DNA looping coupled to LIG3-catalyzed religation; PARylation-dependent acidic microenvironments mediated by the LIG3-YY1 complex facilitate Z-DNA formation, which drives the fusion-religation process for ecDNA generation; PARP inhibitors suppress ecDNA formation. Multi-layer perceptron model, live-cell imaging, proximity ligation assay, PARP inhibitor treatment in human cancer cells, clinical chip verification Molecular cell Medium 40769147
2025 When FEN1 demethylation by JMJD1B is disrupted (R192Q mutation or Jmjd1b-deficient cells), unprocessed 5' flaps accumulate during Okazaki fragment maturation, triggering PARP1-dependent recruitment of LIG3 to join incompletely processed Okazaki fragments; LIG3 has flap ligation activity in this alternative OFM process, which supports cell survival but causes duplication mutations. Mammalian cell genetics (JMJD1b KO, FEN1 R192Q), chromatin immunoprecipitation, PARP1 inhibition, DNA sequencing for mutational analysis bioRxivpreprint Medium 41280084
2025 LIG3α binds nick substrates less frequently but forms longer-lived complexes than LIG1 on canonical A:T nicks, mismatched G:T nicks, and 8-oxoG:A-containing nicks; LIG3α also binds gap DNA but forms short-lived complexes without preference relative to nicks, while LIG1 forms proportionally more stable long-lived complexes on gaps. LIG3α becomes increasingly infrequent on larger gaps. Single-molecule TIRF (total internal reflection fluorescence) microscopy, ensemble ligation assay with purified proteins bioRxivpreprint Medium 40666977
2025 Repair pathway coordination at BER downstream steps requires sequential pol beta gap-filling followed by nick sealing by LIG1 or LIG3α; inaccurate DNA ligation by LIG1/LIG3α from uncoordinated repair with pol beta leads to faulty repair events and deleterious DNA intermediates; XRCC1 as scaffolding factor enhances processivity, and APTX, FEN1, and APE1 clean up ligase-failure products. In vitro BER reconstitution with purified proteins, biochemical coordination assays DNA repair Medium 40081282
2018 Knockout of M-LPH in hepatoma cells causes reduction of LIG3 protein levels in mitochondria (alongside TFAM and OGG1), impairing mitochondrial BER capacity and increasing mtDNA damage, suggesting LIG3 protein stability in mitochondria is dependent on M-LPH. CRISPR-Cas9 knockout, confocal immunofluorescence, Western blot of mitochondrial extracts, PCR-based mtDNA damage quantification Oxidative medicine and cellular longevity Low 30310528

Source papers

Stage 0 corpus · 55 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2013 Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science (New York, N.Y.) 1480 24292625
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2005 Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature 996 15758953
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1996 Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein. The EMBO journal 644 8978692
2001 XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair. Cell 506 11163244
1994 An interaction between the mammalian DNA repair protein XRCC1 and DNA ligase III. Molecular and cellular biology 437 8264637
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2004 AP endonuclease-independent DNA base excision repair in human cells. Molecular cell 403 15260972
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2018 DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity. Cell 379 29656893
2005 Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1. Nature 367 15744309
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2009 Common variants at ten loci influence QT interval duration in the QTGEN Study. Nature genetics 337 19305408
2005 Polymorphisms of DNA repair genes and risk of non-small cell lung cancer. Carcinogenesis 333 16195237
2010 Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells. Molecular cell 310 20227374
1998 DNA ligase IV is essential for V(D)J recombination and DNA double-strand break repair in human precursor lymphocytes. Molecular cell 280 9809069
1995 Characterization of the XRCC1-DNA ligase III complex in vitro and its absence from mutant hamster cells. Nucleic acids research 259 8532526
2014 Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization. Nature genetics 243 24952745
2018 Targeting the MALAT1/PARP1/LIG3 complex induces DNA damage and apoptosis in multiple myeloma. Leukemia 130 29632340
2016 Telomere-Internal Double-Strand Breaks Are Repaired by Homologous Recombination and PARP1/Lig3-Dependent End-Joining. Cell reports 87 27806302
2015 c-MYC Generates Repair Errors via Increased Transcription of Alternative-NHEJ Factors, LIG3 and PARP1, in Tyrosine Kinase-Activated Leukemias. Molecular cancer research : MCR 56 25828893
2013 Structure and function of the DNA ligases encoded by the mammalian LIG3 gene. Gene 53 24013086
2021 HPF1-dependent PARP activation promotes LIG3-XRCC1-mediated backup pathway of Okazaki fragment ligation. Nucleic acids research 44 33872376
2021 Biallelic variants in LIG3 cause a novel mitochondrial neurogastrointestinal encephalomyopathy. Brain : a journal of neurology 39 33855352
2023 CircRNA Galntl6 sponges miR-335 to ameliorate stress-induced hypertension through upregulating Lig3 in rostral ventrolateral medulla. Redox biology 32 37315345
2016 Association between Single-Nucleotide Polymorphisms of the hOGG1,NEIL1,APEX1, FEN1,LIG1, and LIG3 Genes and Alzheimer's Disease Risk. Neuropsychobiology 20 27010693
2019 Sirt3 regulates the level of mitochondrial DNA repair activity through deacetylation of NEIL1, NEIL2, OGG1, MUTYH, APE1 and LIG3 in colorectal cancer. Polski przeglad chirurgiczny 17 32312920
2011 Association between single nucleotide polymorphisms in the DNA repair gene LIG3 and acute adverse skin reactions following radiotherapy. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 16 21620500
2015 Polymorphism of the LIG3 gene in keratoconus and Fuchs endothelial corneal dystrophy. Cellular and molecular biology (Noisy-le-Grand, France) 12 25817347
2021 RAD52 Adjusts Repair of Single-Strand Breaks via Reducing DNA-Damage-Promoted XRCC1/LIG3α Co-localization. Cell reports 11 33440161
2018 Knockout of Mpv17-Like Protein (M-LPH) Gene in Human Hepatoma Cells Results in Impairment of mtDNA Integrity through Reduction of TFAM, OGG1, and LIG3 at the Protein Levels. Oxidative medicine and cellular longevity 6 30310528
2025 Extrachromosomal DNA biogenesis is dependent on DNA looping and religation by YY1-Lig3-PARylation complex. Molecular cell 5 40769147
2019 LIG3 gene polymorphisms and risk of gastric cancer in a Southern Chinese population. Gene 5 31034940
2025 Lig3-dependent rescue of mouse viability and DNA double-strand break repair by catalytically inactive Lig4. Nucleic acids research 3 39673806
2025 Repair pathway coordination from gap filling by polβ and subsequent nick sealing by LIG1 or LIG3α governs BER efficiency at the downstream steps. DNA repair 3 40081282
2025 Nick sealing of polβ mismatch insertion products by LIG1 and LIG3α during 8-oxoG bypass leads to mutagenic or error-free base excision repair. The Journal of biological chemistry 2 40286853
2025 Computational investigation unveils pathogenic LIG3 non-synonymous mutations and therapeutic targets in acute myeloid leukemia. PloS one 2 40493574
2024 Glutamine Supplementation as a Novel Metabolic Therapeutic Strategy for LIG3-Dependent Chronic Intestinal Pseudo-Obstruction. Gastroenterology 2 39173721
2025 JMJD1B-mediated FEN1 demethylation allows timely switching of Okazaki fragment maturation core enzymes to avoid mutagenic flap ligation by PARP1-LIG3. bioRxiv : the preprint server for biology 1 41280084
2024 Mutagenic ligation of polβ mismatch insertion products during 8-oxoG bypass by LIG1 and LIG3α at the downstream steps of base excision repair pathway. bioRxiv : the preprint server for biology 1 39484546
2019 Lack of associations between LIG3 gene polymorphisms and neuroblastoma susceptibility in Chinese children. Journal of Cancer 1 31737108
2026 Novel Biallelic LIG3 Mutations Causing Lethal Phenotype With Immunodeficiency. American journal of medical genetics. Part A 0 41741356
2025 Single-molecule analysis of gap and nick binding by LIG1 and LIG3α at the final step of DNA repair. bioRxiv : the preprint server for biology 0 40666977