ArticleThe Journal of biological chemistry2014
DNA sequences proximal to human mitochondrial DNA deletion breakpoints prevalent in human disease form G-quadruplexes, a class of DNA structures inefficiently unwound by the mitochondrial replicative Twinkle helicase.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 135 citations in OpenAlex.
- Article
- Rare genetic diseases associated with G-quadruplex-induced replication stress.Communications biology · 2026Review
- Periosteal mitochondria DNA structures drive aging-associated poor skeletal repair.Bone research · 2026Article
- G-quadruplex ligand RHPS4 compromises cellular radioresistance by inhibiting the mitochondrial adaptive response induced by ionizing irradiation.NAR cancer · 2025Article
- Predictability of environment-dependent formation of G-quadruplex DNAs in human mitochondria.Communications chemistry · 2025Article
- DNA repair pathways in the mitochondria.DNA repair · 2025Review
- The 9 bp Deletion between the Mitochondrial COII and Lysine tRNA Genes in a Caucasian Population with Cognitive Disorders: An Observational Study.International journal of molecular sciences · 2024Observational
- Eukaryotic Pif1 helicase unwinds G-quadruplex and dsDNA using a conserved wedge.Nature communications · 2024Article
- Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation.The Biochemical journal · 2024Review
- G-quadruplex propensity inNAR genomics and bioinformatics · 2024Article
- A G-quadruplex-binding platinum complex induces cancer mitochondrial dysfunction through dual-targeting mitochondrial and nuclear G4 enriched genome.Journal of biomedical science · 2024Article
- Mitochondrial nucleic acids in innate immunity and beyond.Experimental & molecular medicine · 2023Review
- Enhanced mitochondrial G-quadruplex formation impedes replication fork progression leading to mtDNA loss in human cells.Nucleic acids research · 2023Article
- Exploring the G-quadruplex binding and unwinding activity of the bacterial FeS helicase DinG.Scientific reports · 2023Article
- Mitochondria and G-quadruplex evolution: an intertwined relationship.Trends in genetics : TIG · 2023Review
- Article
- Biochemical analysis of DNA synthesis blockage by G-quadruplex structure and bypass facilitated by a G4-resolving helicase.Methods (San Diego, Calif.) · 2022Article
- Role and Regulation of Pif1 Family Helicases at the Replication Fork.International journal of molecular sciences · 2022Review
- A complementary chemical probe approach towards customized studies of G-quadruplex DNA structures in live cells.Chemical science · 2022Article
- Spectroscopic Characterization of Mitochondrial G-Quadruplexes.International journal of molecular sciences · 2022Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 4 countries.
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Abstract
Mitochondrial DNA deletions are prominent in human genetic disorders, cancer, and aging. It is thought that stalling of the mitochondrial replication machinery during DNA synthesis is a prominent source of mitochondrial genome instability; however, the precise molecular determinants of defective mitochondrial replication are not well understood. In this work, we performed a computational analysis of the human mitochondrial genome using the "Pattern Finder" G-quadruplex (G4) predictor algorithm to assess whether G4-forming sequences reside in close proximity (within 20 base pairs) to known mitochondrial DNA deletion breakpoints. We then used this information to map G4P sequences with deletions characteristic of representative mitochondrial genetic disorders and also those identified in various cancers and aging. Circular dichroism and UV spectral analysis demonstrated that mitochondrial G-rich sequences near deletion breakpoints prevalent in human disease form G-quadruplex DNA structures. A biochemical analysis of purified recombinant human Twinkle protein (gene product of c10orf2) showed that the mitochondrial replicative helicase inefficiently unwinds well characterized intermolecular and intramolecular G-quadruplex DNA substrates, as well as a unimolecular G4 substrate derived from a mitochondrial sequence that nests a deletion breakpoint described in human renal cell carcinoma. Although G4 has been implicated in the initiation of mitochondrial DNA replication, our current findings suggest that mitochondrial G-quadruplexes are also likely to be a source of instability for the mitochondrial genome by perturbing the normal progression of the mitochondrial replication machinery, including DNA unwinding by Twinkle helicase.
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