ArticleThe Journal of biological chemistry2016
Biochemical Characterization of the Human Mitochondrial Replicative Twinkle Helicase: SUBSTRATE SPECIFICITY, DNA BRANCH MIGRATION, AND ABILITY TO OVERCOME BLOCKADES TO DNA UNWINDING.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- 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
- 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
- Penetrance of pathogenic genetic variants associated with premature ovarian insufficiency.Nature medicine · 2023Article
- Structural and dynamic basis of DNA capture and translocation by mitochondrial Twinkle helicase.Nucleic acids research · 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
- DNA polymerase β outperforms DNA polymerase γ in key mitochondrial base excision repair activities.DNA repair · 2021Article
- FANCJ compensates for RAP80 deficiency and suppresses genomic instability induced by interstrand cross-links.Nucleic acids research · 2020Article
- Mitochondrial genetic variation is enriched in G-quadruplex regions that stall DNA synthesis in vitro.Human molecular genetics · 2020Article
- Single-molecule level structural dynamics of DNA unwinding by human mitochondrial Twinkle helicase.The Journal of biological chemistry · 2020Article
- Review
- Replication fork rescue in mammalian mitochondria.Scientific reports · 2019Article
- Bacterial DnaB helicase interacts with the excluded strand to regulate unwinding.The Journal of biological chemistry · 2017Article
- Mechanistic insights into how CMG helicase facilitates replication past DNA roadblocks.DNA repair · 2017Review
- 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
9 authors at 5 institutions in 1 country.
Funding
Abstract
Mutations in the c10orf2 gene encoding the human mitochondrial DNA replicative helicase Twinkle are linked to several rare genetic diseases characterized by mitochondrial defects. In this study, we have examined the catalytic activity of Twinkle helicase on model replication fork and DNA repair structures. Although Twinkle behaves as a traditional 5' to 3' helicase on conventional forked duplex substrates, the enzyme efficiently dissociates D-loop DNA substrates irrespective of whether it possesses a 5' or 3' single-stranded tailed invading strand. In contrast, we report for the first time that Twinkle branch-migrates an open-ended mobile three-stranded DNA structure with a strong 5' to 3' directionality preference. To determine how well Twinkle handles potential roadblocks to mtDNA replication, we tested the ability of the helicase to unwind substrates with site-specific oxidative DNA lesions or bound by the mitochondrial transcription factor A. Twinkle helicase is inhibited by DNA damage in a unique manner that is dependent on the type of oxidative lesion and the strand in which it resides. Novel single molecule FRET binding and unwinding assays show an interaction of the excluded strand with Twinkle as well as events corresponding to stepwise unwinding and annealing. TFAM inhibits Twinkle unwinding, suggesting other replisome proteins may be required for efficient removal. These studies shed new insight on the catalytic functions of Twinkle on the key DNA structures it would encounter during replication or possibly repair of the mitochondrial genome and how well it tolerates potential roadblocks to DNA unwinding.
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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.