ArticleNucleic acids research2016
Homologous DNA strand exchange activity of the human mitochondrial DNA helicase TWINKLE.
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 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Human mitochondrial helicase Twinkle has RNA binding, annealing, and strand-exchange activities.Nucleic acids research · 2026Article
- Mitochondrial DNA Replication and Disease: A Historical Perspective on Molecular Insights and Therapeutic Advances.International journal of molecular sciences · 2025Review
- The First HeterozygousBiomolecules · 2025Article
- Single-molecule fluorescence reveals the DNA unwinding mechanism of mitochondrial helicase TWINKLE and its interplay with single-stranded DNA-binding proteins.Nucleic acids research · 2025Article
- Autoregulation of the real-time kinetics of the human mitochondrial replicative helicase.Nature communications · 2025Article
- Linear DNA-driven recombination in mammalian mitochondria.Nucleic acids research · 2024Article
- Article
- Twinkle-Catalyzed Toehold-Mediated DNA Strand Displacement Reaction.Journal of the American Chemical Society · 2023Article
- Structural and Molecular Basis for Mitochondrial DNA Replication and Transcription in Health and Antiviral Drug Toxicity.Molecules (Basel, Switzerland) · 2023Review
- The N-terminal domain of human mitochondrial helicase Twinkle has DNA-binding activity crucial for supporting processive DNA synthesis by polymerase γ.The Journal of biological chemistry · 2023Article
- Mitochondrial DNA maintenance in Drosophila melanogaster.Bioscience reports · 2022Review
- Mitochondrial DNA Instability in Mammalian Cells.Antioxidants & redox signaling · 2022Review
- Mitochondrial DNA damage as driver of cellular outcomes.American journal of physiology. Cell physiology · 2022Review
- Thermodynamic analysis of DNA hybridization signatures near mitochondrial DNA deletion breakpoints.iScience · 2021Article
- Review
- Roles of the mitochondrial replisome in mitochondrial DNA deletion formation.Genetics and molecular biology · 2020Article
- Replication fork rescue in mammalian mitochondria.Scientific reports · 2019Article
- Twist and Turn-Topoisomerase Functions in Mitochondrial DNA Maintenance.International journal of molecular sciences · 2019Review
- Structural rearrangements in the mitochondrial genome of Drosophila melanogaster induced by elevated levels of the replicative DNA helicase.Nucleic acids research · 2018Article
- Mechanistic and biological considerations of oxidatively damaged DNA for helicase-dependent pathways of nucleic acid metabolism.Free radical biology & medicine · 2017Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
A crucial component of the human mitochondrial DNA replisome is the ring-shaped helicase TWINKLE-a phage T7-gene 4-like protein expressed in the nucleus and localized in the human mitochondria. Our previous studies showed that despite being a helicase, TWINKLE has unique DNA annealing activity. At the time, the implications of DNA annealing by TWINKLE were unclear. Herein, we report that TWINKLE uses DNA annealing function to actively catalyze strand-exchange reaction between the unwinding substrate and a homologous single-stranded DNA. Using various biochemical experiments, we demonstrate that the mechanism of strand-exchange involves active coupling of unwinding and annealing reactions by the TWINKLE. Unlike strand-annealing, the strand-exchange reaction requires nucleotide hydrolysis and greatly stimulated by short region of homology between the recombining DNA strands that promote joint molecule formation to initiate strand-exchange. Furthermore, we show that TWINKLE catalyzes branch migration by resolving homologous four-way junction DNA. These four DNA modifying activities of TWINKLE: strand-separation, strand-annealing, strand-exchange and branch migration suggest a dual role of TWINKLE in mitochondrial DNA maintenance. In addition to playing a major role in fork progression during leading strand DNA synthesis, we propose that TWINKLE is involved in recombinational repair of the human mitochondrial DNA.
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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.