ArticleThe Journal of biological chemistry2011
Kinetic mechanism of human DNA ligase I reveals magnesium-dependent changes in the rate-limiting step that compromise ligation efficiency.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- Nature Counts to Three: Universal Mg-Pinch Motif Polarizes the Cleaved Bond in NTP-Processing Enzymes.Journal of the American Chemical Society · 2026Article
- 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
- Potent inhibitors of the human RNA ligase Rlig1 highlights its role in RNA integrity maintenance under oxidative cellular stress.Chemical science · 2025Article
- Yaravirus brasiliense genomic structure analysis and its possible influence on the metabolism.Genetics and molecular biology · 2025Article
- Association of magnesium deficiency scores with risk of rheumatoid arthritis and osteoarthritis in adults: a cross-sectional population-based study.Clinical rheumatology · 2024Article
- Probing the mechanism of nick searching by LIG1 at the single-molecule level.Nucleic acids research · 2024Article
- Characterisation and engineering of a thermophilic RNA ligase from Palaeococcus pacificus.Nucleic acids research · 2024Article
- Human DNA ligases I and III have stand-alone end-joining capability, but differ in ligation efficiency and specificity.Nucleic acids research · 2023Article
- Obstacles and opportunities for base excision repair in chromatin.DNA repair · 2022Review
- LIG1 syndrome mutations remodel a cooperative network of ligand binding interactions to compromise ligation efficiency.Nucleic acids research · 2021Article
- Two-tiered enforcement of high-fidelity DNA ligation.Nature communications · 2019Article
- Interplay between DNA Polymerases and DNA Ligases: Influence on Substrate Channeling and the Fidelity of DNA Ligation.Journal of molecular biology · 2019Review
- DNA Ligase 1 is an essential mediator of sister chromatid telomere fusions in G2 cell cycle phase.Nucleic acids research · 2019Article
- Biallelic mutations in DNA ligase 1 underlie a spectrum of immune deficiencies.The Journal of clinical investigation · 2018Article
- Structures of DNA-bound human ligase IV catalytic core reveal insights into substrate binding and catalysis.Nature communications · 2018Article
- Kinetic analyses of single-stranded break repair by human DNA ligase III isoforms reveal biochemical differences from DNA ligase I.The Journal of biological chemistry · 2017Article
- Kinetic mechanism and fidelity of nick sealing by Escherichia coli NAD+-dependent DNA ligase (LigA).Nucleic acids research · 2016Article
- The Inhibitory Effect of Non-Substrate and Substrate DNA on the Ligation and Self-Adenylylation Reactions Catalyzed by T4 DNA Ligase.PloS one · 2016Article
- Human DNA ligase III bridges two DNA ends to promote specific intermolecular DNA end joining.Nucleic acids research · 2015Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA ligase I (LIG1) catalyzes the ligation of single-strand breaks to complete DNA replication and repair. The energy of ATP is used to form a new phosphodiester bond in DNA via a reaction mechanism that involves three distinct chemical steps: enzyme adenylylation, adenylyl transfer to DNA, and nick sealing. We used steady state and pre-steady state kinetics to characterize the minimal mechanism for DNA ligation catalyzed by human LIG1. The ATP dependence of the reaction indicates that LIG1 requires multiple Mg(2+) ions for catalysis and that an essential Mg(2+) ion binds more tightly to ATP than to the enzyme. Further dissection of the magnesium ion dependence of individual reaction steps revealed that the affinity for Mg(2+) changes along the reaction coordinate. At saturating concentrations of ATP and Mg(2+) ions, the three chemical steps occur at similar rates, and the efficiency of ligation is high. However, under conditions of limiting Mg(2+), the nick-sealing step becomes rate-limiting, and the adenylylated DNA intermediate is prematurely released into solution. Subsequent adenylylation of enzyme prevents rebinding to the adenylylated DNA intermediate comprising an Achilles' heel of LIG1. These ligase-generated 5'-adenylylated nicks constitute persistent breaks that are a threat to genomic stability if they are not repaired. The kinetic and thermodynamic framework that we have determined for LIG1 provides a starting point for understanding the mechanism and specificity of mammalian DNA ligases.
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