ArticleNucleic acids research2022
Two type I topoisomerases maintain DNA topology in human mitochondria.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Proteolytic cleavage activates the mitochondrial isoform of TOP3A.Nucleic acids research · 2025Article
- Ligase 3 prevents oxidative strand break-induced mitochondrial DNA loss but is not essential for replicative circularization.Nucleic acids research · 2025Article
- The low endoribonuclease activity and lack of rNMP preference of human mitochondrial topoisomerase 1 protect against ribonucleotide-dependent deletions.Nucleic acids research · 2025Article
- Deciphering linezolid-induced hematologic toxicity: Targeting TOP2A and TOP2B via its primary metabolite PNU142586.Science advances · 2025Article
- Role of Z-DNA Binding Protein 1 Sensing Mitochondrial Z-DNA and Triggering Necroptosis in Oxalate-Induced Acute Kidney Injury.Journal of the American Society of Nephrology : JASN · 2025Article
- Mitochondrial topoisomerase I (Top1MT) prevents the onset of metabolic dysfunction-associated steatohepatitis (MASH) in mice.bioRxiv : the preprint server for biology · 2024Article
- Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation.The Biochemical journal · 2024Review
- Sensing of mitochondrial DNA by ZBP1 promotes RIPK3-mediated necroptosis and ferroptosis in response to diquat poisoning.Cell death and differentiation · 2024Article
- Variation of Structure and Cellular Functions of Type IA Topoisomerases across the Tree of Life.Cells · 2024Review
- Deficiency of TOP1MT enhances glycolysis through the stimulation of PDK4 expression in gastric cancer.Cancer & metabolism · 2024Article
- TOP3A coupling with replication forks and repair of TOP3A cleavage complexes.Cell cycle (Georgetown, Tex.) · 2024Review
- Article
- Pathological variants in TOP3A cause distinct disorders of mitochondrial and nuclear genome stability.EMBO molecular medicine · 2023Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Genetic processes require the activity of multiple topoisomerases, essential enzymes that remove topological tension and intermolecular linkages in DNA. We have investigated the subcellular localisation and activity of the six human topoisomerases with a view to understanding the topological maintenance of human mitochondrial DNA. Our results indicate that mitochondria contain two topoisomerases, TOP1MT and TOP3A. Using molecular, genomic and biochemical methods we find that both proteins contribute to mtDNA replication, in addition to the decatenation role of TOP3A, and that TOP1MT is stimulated by mtSSB. Loss of TOP3A or TOP1MT also dysregulates mitochondrial gene expression, and both proteins promote transcription elongation in vitro. We find no evidence for TOP2 localisation to mitochondria, and TOP2B knockout does not affect mtDNA maintenance or expression. Our results suggest a division of labour between TOP3A and TOP1MT in mtDNA topology control that is required for the proper maintenance and expression of human mtDNA.
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