ArticleThe Journal of biological chemistry2020
Single-molecule level structural dynamics of DNA unwinding by human mitochondrial Twinkle helicase.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 19 citations in OpenAlex.
- Analysis of DNA-Protein Complexes by Atomic Force Microscopy Imaging: The Case of TRF2-Telomeric DNA Wrapping.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Structural and single-molecule insights into the core human mitochondrial DNA replisome.The Biochemical journal · 2026Review
- Smc5/6 uses its head-NSE module to preferentially associate with ssDNA gaps and ss-dsDNA junctions.Nucleic acids research · 2026Article
- Higher-order structural organization of mitochondrial metabolism.The Journal of biological chemistry · 2026Review
- Mitochondrial DNA Replication and Disease: A Historical Perspective on Molecular Insights and Therapeutic Advances.International journal of molecular sciences · 2025Review
- 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
- Structures of the mitochondrial single-stranded DNA binding protein with DNA and DNA polymerase γ.Nucleic acids research · 2024Article
- Structure-specific roles for PolG2-DNA complexes in maintenance and replication of mitochondrial DNA.Nucleic acids research · 2023Article
- Single-molecule imaging of genome maintenance proteins encountering specific DNA sequences and structures.DNA repair · 2023Review
- Structural and dynamic basis of DNA capture and translocation by mitochondrial Twinkle helicase.Nucleic acids research · 2022Article
- Method for the structural analysis of Twinkle mitochondrial DNA helicase by cryo-EM.Methods (San Diego, Calif.) · 2022Article
- Structural insight and characterization of human Twinkle helicase in mitochondrial disease.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Using Atomic Force Microscopy to Study the Real Time Dynamics of DNA Unwinding by Mitochondrial Twinkle Helicase.Bio-protocol · 2021Article
- Synthesis and application of aRSC chemical biology · 2021Article
- DNA replication machinery: Insights fromComputational and structural biotechnology journal · 2021Review
- Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Knowledge of the molecular events in mitochondrial DNA (mtDNA) replication is crucial to understanding the origins of human disorders arising from mitochondrial dysfunction. Twinkle helicase is an essential component of mtDNA replication. Here, we employed atomic force microscopy imaging in air and liquids to visualize ring assembly, DNA binding, and unwinding activity of individual Twinkle hexamers at the single-molecule level. We observed that the Twinkle subunits self-assemble into hexamers and higher-order complexes that can switch between open and closed-ring configurations in the absence of DNA. Our analyses helped visualize Twinkle loading onto and unloading from DNA in an open-ringed configuration. They also revealed that closed-ring conformers bind and unwind several hundred base pairs of duplex DNA at an average rate of ∼240 bp/min. We found that the addition of mitochondrial single-stranded (ss) DNA-binding protein both influences the ways Twinkle loads onto defined DNA substrates and stabilizes the unwound ssDNA product, resulting in a ∼5-fold stimulation of the apparent DNA-unwinding rate. Mitochondrial ssDNA-binding protein also increased the estimated translocation processivity from 1750 to >9000 bp before helicase disassociation, suggesting that more than half of the mitochondrial genome could be unwound by Twinkle during a single DNA-binding event. The strategies used in this work provide a new platform to examine Twinkle disease variants and the core mtDNA replication machinery. They also offer an enhanced framework to investigate molecular mechanisms underlying deletion and depletion of the mitochondrial genome as observed in mitochondrial diseases.
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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.