ArticleNucleic acids research2022
Top3α is the replicative topoisomerase in mitochondrial DNA replication.
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 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- The Roles of Topoisomerases in Transcriptional Regulation.International journal of molecular sciences · 2026Review
- Differential roles of type I topoisomerases in regulating HPV pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Identification of aFrontiers in pharmacology · 2026Article
- Mitochondrial DNA Replication and Disease: A Historical Perspective on Molecular Insights and Therapeutic Advances.International journal of molecular sciences · 2025Review
- Ligase 3 prevents oxidative strand break-induced mitochondrial DNA loss but is not essential for replicative circularization.Nucleic acids research · 2025Article
- Topoisomerase IIIα controls alternative lengthening of telomeres.Cell reports · 2025Article
- MRE11-independent effects of Mirin on mitochondrial DNA integrity and cellular immune responses.Molecular biology of the cell · 2025Article
- Mitochondrial DNA depletion syndrome and its cardiac complication.Frontiers in cardiovascular medicine · 2025Review
- Alternative translation initiation by ribosomal leaky scanning produces multiple isoforms of the Pif1 helicase.Nucleic acids research · 2024Article
- Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation.The Biochemical journal · 2024Review
- Linear DNA-driven recombination in mammalian mitochondria.Nucleic acids research · 2024Article
- Variation of Structure and Cellular Functions of Type IA Topoisomerases across the Tree of Life.Cells · 2024Review
- TOP3A coupling with replication forks and repair of TOP3A cleavage complexes.Cell cycle (Georgetown, Tex.) · 2024Review
- Let's make it clear: systematic exploration of mitochondrial DNA- and RNA-protein complexes by complexome profiling.Nucleic acids research · 2023Article
- Uncharacterized protein C17orf80 - a novel interactor of human mitochondrial nucleoids.Journal of cell science · 2023Article
- 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
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial DNA has been investigated for nearly fifty years, but many aspects of the maintenance of this essential small genome remain unknown. Like any genome, mammalian mitochondrial DNA requires the function of topoisomerases to counter and regulate the topological tension arising during replication, transcription, segregation, and repair. However, the functions of the different mitochondrial topoisomerases are poorly understood. Here, we investigate the role of Topoisomerase 3α (Top3α) in mtDNA replication and transcription, providing evidence that this enzyme, previously reported to act in mtDNA segregation, also participates in mtDNA replication fork progression. Top3α knockdown caused replication fork stalling, increased mtDNA catenation and decreased mtDNA levels. Overexpression in contrast induced abundant double-strand breaks around the replication origin OH and abortion of early replication, while at the same time improving the resolution of mtDNA replication termination intermediates. Both Top3α knockdown and overexpression affected mitochondrial RNA transcription, leading to a decrease in steady-state levels of mitochondrial transcripts. Together, our results indicate that the mitochondrial isoform of Top3α is not only involved in mtDNA segregation, as reported previously, but also supports the progression of the replication fork. Mitochondrial Top3α is also influencing the progression of transcription, with its absence affecting downstream transcript levels.
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