ArticleNucleic acids research2016
MGME1 processes flaps into ligatable nicks in concert with DNA polymerase γ during mtDNA replication.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- High-concentration MEHP triggers mtDNA depletion in undifferentiated HepaRG and C2C12 cultures and disrupts mitochondrial homeostasis in both HepaRG culture states.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Ligase 3 prevents oxidative strand break-induced mitochondrial DNA loss but is not essential for replicative circularization.Nucleic acids research · 2025Article
- Disruption of mitochondrial DNA integrity in cardiomyocyte injury upon ischemia/reperfusion.Genes & diseases · 2025Review
- Mitochondrial exonuclease EXOG supports DNA integrity by the removal of single-stranded DNA flaps.Nucleic acids research · 2025Article
- Mechanisms underlining R-loop biology and implications for human disease.Frontiers in cell and developmental biology · 2025Review
- Nuclease-induced stepwise photodropping (NISP) to precisely investigate single-stranded DNA degradation behaviors of exonucleases and endonucleases.Nucleic acids research · 2024Article
- Integrative multi-omics analysis unveils the connection between transcriptomic characteristics associated with mitochondria and the tumor immune microenvironment in lower-grade gliomas.Scientific reports · 2024Article
- Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation.The Biochemical journal · 2024Review
- Structural basis of how MGME1 processes DNA 5' ends to maintain mitochondrial genome integrity.Nucleic acids research · 2024Article
- Mitochondrial Chronic Progressive External Ophthalmoplegia.Brain sciences · 2024Review
- Structure-specific roles for PolG2-DNA complexes in maintenance and replication of mitochondrial DNA.Nucleic acids research · 2023Article
- Maintenance of Flap Endonucleases for Long-Patch Base Excision DNA Repair in Mouse Muscle and Neuronal Cells Differentiated In Vitro.International journal of molecular sciences · 2023Article
- Article
- MGME1 associates with poor prognosis and is vital for cell proliferation in lower-grade glioma.Aging · 2023Article
- Mechanism of strand displacement DNA synthesis by the coordinated activities of human mitochondrial DNA polymerase and SSB.Nucleic acids research · 2023Article
- Unravelling How Single-Stranded DNA Binding Protein Coordinates DNA Metabolism Using Single-Molecule Approaches.International journal of molecular sciences · 2023Review
- Nuclear genetic control of mtDNA copy number and heteroplasmy in humans.medRxiv : the preprint server for health sciences · 2023Article
- Method for the structural analysis of Twinkle mitochondrial DNA helicase by cryo-EM.Methods (San Diego, Calif.) · 2022Article
- In vitro reconstitution reveals a key role of human mitochondrial EXOG in RNA primer processing.Nucleic acids research · 2022Article
- Mice lacking the mitochondrial exonuclease MGME1 develop inflammatory kidney disease with glomerular dysfunction.PLoS genetics · 2022Article
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, MGME1 was identified as a mitochondrial DNA nuclease with preference for single-stranded DNA (ssDNA) substrates. Loss-of-function mutations in patients lead to mitochondrial disease with DNA depletion, deletions, duplications and rearrangements. Here, we assess the biochemical role of MGME1 in the processing of flap intermediates during mitochondrial DNA replication using reconstituted systems. We show that MGME1 can cleave flaps to enable efficient ligation of newly replicated DNA strands in combination with POLγ. MGME1 generates a pool of imprecisely cut products (short flaps, nicks and gaps) that are converted to ligatable nicks by POLγ through extension or excision of the 3'-end strand. This is dependent on the 3'-5' exonuclease activity of POLγ which limits strand displacement activity and enables POLγ to back up to the nick by 3'-5' degradation. We also demonstrate that POLγ-driven strand displacement is sufficient to generate DNA- but not RNA-flap substrates suitable for MGME1 cleavage and ligation during replication. Our findings have implications for RNA primer removal models, the 5'-end processing of nascent DNA at OriH, and DNA repair.
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