ArticleNucleic acids research2019
Human DNA ligase IV is able to use NAD+ as an alternative adenylation donor for DNA ends ligation.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
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- Nicotinamide N-methyltransferase and liver diseases.Genes & diseases · 2023Review
- BRCT Domains: Structure, Functions, and Implications in Disease-New Therapeutic Targets for Innovative Drug Discovery against Infections.Pharmaceutics · 2023Review
- Article
- Catalytically inactive DNA ligase IV promotes DNA repair in living cells.Nucleic acids research · 2022Article
- Fueling genome maintenance: On the versatile roles of NADThe Journal of biological chemistry · 2022Review
- NADMolecular and cellular biochemistry · 2022Review
- Nicotinamide adenine dinucleotide metabolism in the immune response, autoimmunity and inflammageing.British journal of pharmacology · 2022Review
- LDH-A inhibitors as remedies to enhance the anticancer effects of PARP inhibitors in ovarian cancer cells.Aging · 2021Article
- BST1 regulates nicotinamide riboside metabolism via its glycohydrolase and base-exchange activities.Nature communications · 2021Article
- DNA Damage-Induced Neurodegeneration in Accelerated Ageing and Alzheimer's Disease.International journal of molecular sciences · 2021Review
- The Emerging Role of RNA Modifications in DNA Double-Strand Break Repair.Frontiers in molecular biosciences · 2021Review
- Nicotinamide Mononucleotide Attenuates Renal Interstitial Fibrosis After AKI by Suppressing Tubular DNA Damage and Senescence.Frontiers in physiology · 2021Article
- NAD+ is not utilized as a co-factor for DNA ligation by human DNA ligase IV.Nucleic acids research · 2020Article
- The molecular basis and disease relevance of non-homologous DNA end joining.Nature reviews. Molecular cell biology · 2020Review
- NADSignal transduction and targeted therapy · 2020Review
- (ADP-ribosyl)hydrolases: structure, function, and biology.Genes & development · 2020Review
- Altered DNA ligase activity in human disease.Mutagenesis · 2020Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
All the eukaryotic DNA ligases are known to use adenosine triphosphate (ATP) for DNA ligation. Here, we report that human DNA ligase IV, a key enzyme in DNA double-strand break (DSB) repair, is able to use NAD+ as a substrate for double-stranded DNA ligation. In the in vitro ligation assays, we show that the recombinant Ligase IV can use both ATP and NAD+ for DNA ligation. For NAD+-mediated ligation, the BRCA1 C-terminal (BRCT) domain of Ligase IV recognizes NAD+ and facilitates the adenylation of Ligase IV, the first step of ligation. Although XRCC4, the functional partner of Ligase IV, is not required for the NAD+-mediated adenylation, it regulates the transfer of AMP moiety from Ligase IV to the DNA end. Moreover, cancer-associated mutation in the BRCT domain of Ligase IV disrupts the interaction with NAD+, thus abolishes the NAD+-mediated adenylation of Ligase IV and DSB ligation. Disrupting the NAD+ recognition site in the BRCT domain impairs non-homologous end joining (NHEJ) in cell. Taken together, our study reveals that in addition to ATP, Ligase IV may use NAD+ as an alternative adenylation donor for NHEJ repair and maintaining genomic stability.
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Registered trials
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