ArticleNucleic acids research2025
Single-molecule fluorescence reveals the DNA unwinding mechanism of mitochondrial helicase TWINKLE and its interplay with single-stranded DNA-binding proteins.
Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
3 citing papers in PubMed.
- Structural and single-molecule insights into the core human mitochondrial DNA replisome.The Biochemical journal · 2026Review
- 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
The mitochondrial DNA helicase TWINKLE, a hexameric ring-shaped helicase, plays a crucial role in maintaining mitochondrial DNA integrity. TWINKLE translocates along one DNA strand, unwinding the duplex by excluding the complementary strand through coordinated ATP hydrolysis. However, the precise mechanisms underlying this process remain incompletely understood. In this study, we utilized single-molecule Förster Resonance Energy Transfer (smFRET) to investigate the mechanisms of TWINKLE-mediated DNA unwinding. Our results reveal that TWINKLE occasionally pauses during unwinding, with the rate of unwinding and the duration of pausing strongly influenced by ATP concentration, but not by the presence of DNA mismatches or mitochondrial single-stranded DNA-binding protein (mtSSB). These findings suggest that the pausing events primarily arise from stochastic ATP hydrolysis within the helicase subunits. DNA mismatches exacerbate TWINKLE's pausing and dissociation from DNA, thereby impairing DNA unwinding. In contrast, mtSSB significantly mitigates helicase dissociation by stabilizing TWINKLE-DNA interactions. This study provides novel insights into the functional dynamics of TWINKLE, highlighting the role of ATP hydrolysis in orchestrating single-stranded DNA translocation, the detrimental effects of DNA mismatches on DNA unwinding, and the critical role of mtSSB in supporting helicase function.
Indexed as
Identifiers
What OpenQuestion holds
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.