ArticleThe Journal of biological chemistry2013
Mitochondrial DNA ligase is dispensable for the viability of cultured cells but essential for mtDNA maintenance.
Article in The Journal of biological chemistry, 2013. 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, 35 citations in OpenAlex.
- Novel Biallelic LIG3 Mutations Causing Lethal Phenotype With Immunodeficiency.American journal of medical genetics. Part A · 2026Article
- Ligase 3 prevents oxidative strand break-induced mitochondrial DNA loss but is not essential for replicative circularization.Nucleic acids research · 2025Article
- Decoding mitochondrial DNA damage and repair associated withFrontiers in cellular and infection microbiology · 2024Review
- Article
- The C-Terminal Tail of Mitochondrial Transcription Factor A Is Dispensable for Mitochondrial DNA Replication and Transcription In Situ.International journal of molecular sciences · 2023Article
- Generation of Mammalian Cells Devoid of Mitochondrial DNA (ρCurrent protocols · 2023Article
- TFAM's Contributions to mtDNA Replication and OXPHOS Biogenesis Are Genetically Separable.Cells · 2022Article
- Article
- Article
- Mitochondrial Neurodegeneration.Cells · 2022Review
- Myopathic mitochondrial DNA depletion syndrome associated with biallelic variants in LIG3.Brain : a journal of neurology · 2021Article
- Limited predictive value of TFAM in mitochondrial biogenesis.Mitochondrion · 2019Article
- Article
- Structures of DNA-bound human ligase IV catalytic core reveal insights into substrate binding and catalysis.Nature communications · 2018Article
- Elimination of Mitochondrial DNA from Mammalian Cells.Current protocols in cell biology · 2018Article
- DNA repair after oxidative stress: current challenges.Current opinion in toxicology · 2018Article
- PNPase knockout results in mtDNA loss and an altered metabolic gene expression program.PloS one · 2018Article
- Inhibiting Mitochondrial DNA Ligase IIIα Activates Caspase 1-Dependent Apoptosis in Cancer Cells.Cancer research · 2016Article
- Mitochondrial DNA damage induced autophagy, cell death, and disease.Frontiers in bioscience (Landmark edition) · 2016Review
- The "fast" and the "slow" modes of mitochondrial DNA degradation.Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Multiple lines of evidence support the notion that DNA ligase III (LIG3), the only DNA ligase found in mitochondria, is essential for viability in both whole organisms and in cultured cells. Previous attempts to generate cells devoid of mitochondrial DNA ligase failed. Here, we report, for the first time, the derivation of viable LIG3-deficient mouse embryonic fibroblasts. These cells lack mtDNA and are auxotrophic for uridine and pyruvate, which may explain the apparent lethality of the Lig3 knock-out observed in cultured cells in previous studies. Cells with severely reduced expression of LIG3 maintain normal mtDNA copy number and respiration but show reduced viability in the face of alkylating and oxidative damage, increased mtDNA degradation in response to oxidative damage, and slow recovery from mtDNA depletion. Our findings clarify the cellular role of LIG3 and establish that the loss of viability in LIG3-deficient cells is conditional and secondary to the ρ(0) phenotype.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.