ArticleNucleic acids research2021
LIG1 syndrome mutations remodel a cooperative network of ligand binding interactions to compromise ligation efficiency.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 25 citations in OpenAlex.
- Fidelity of DNA ligase I is sensitive to physiological MgThe Journal of biological chemistry · 2026Article
- Huntington's disease LIG1 modifier variant increases ligase fidelity and suppresses somatic CAG repeat expansion.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Impaired nick recognition and ligation efficiency by LIG1 K845N variant linked to Huntington's disease.NAR molecular medicine · 2025Article
- Histone Lactylation Antagonizes Senescence and Skeletal Muscle Aging by Modulating Aging-Related Pathways.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mammalian DNA ligases; roles in maintaining genome integrity.Journal of molecular biology · 2024Review
- Next-Generation Sequencing in the Assessment of the Transcriptomic Landscape of DNA Damage Repair Genes in Abdominal Aortic Aneurysm, Chronic Venous Disease and Lower Extremity Artery Disease.International journal of molecular sciences · 2022Article
- Mechanistic investigation of human maturation of Okazaki fragments reveals slow kinetics.Nature communications · 2022Article
- Structures of LIG1 that engage with mutagenic mismatches inserted by polβ in base excision repair.Nature communications · 2022Article
- MEFV, IRF8, ADA, PEPD, and NBAS gene variants and elevated serum cytokines in a patient with unilateral sporadic Meniere's disease and vascular congestion over the endolymphatic sac.Journal of otology · 2022Article
- Cryo-EM structures and biochemical insights into heterotrimeric PCNA regulation of DNA ligase.Structure (London, England : 1993) · 2022Article
- Case report: Severe combined immunodeficiency with ligase 1 deficiency and Omenn-like manifestation.Frontiers in immunology · 2022Article
- DNA ligase I fidelity mediates the mutagenic ligation of pol β oxidized and mismatch nucleotide insertion products in base excision repair.The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Human DNA ligase I (LIG1) is the main replicative ligase and it also seals DNA breaks to complete DNA repair and recombination pathways. Immune compromised patients harbor hypomorphic LIG1 alleles encoding substitutions of conserved arginine residues, R771W and R641L, that compromise LIG1 activity through poorly defined mechanisms. To understand the molecular basis of LIG1 syndrome mutations, we determined high resolution X-ray structures and performed systematic biochemical characterization of LIG1 mutants using steady-state and pre-steady state kinetic approaches. Our results unveil a cooperative network of plastic DNA-LIG1 interactions that connect DNA substrate engagement with productive binding of Mg2+ cofactors for catalysis. LIG1 syndrome mutations destabilize this network, compromising Mg2+ binding affinity, decreasing ligation efficiency, and leading to elevated abortive ligation that may underlie the disease pathology. These findings provide novel insights into the fundamental mechanism by which DNA ligases engage with a nicked DNA substrate, and they suggest that disease pathology of LIG1 syndrome could be modulated by Mg2+ levels.
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