ArticleNucleic acids research2023
Enhanced mitochondrial G-quadruplex formation impedes replication fork progression leading to mtDNA loss in human cells.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 45 citations in OpenAlex.
- Repeat-length variation generates stable TTGGG-family G-quadruplex motifs in plant mitochondrial genomes.Planta · 2026Article
- Article
- Rare genetic diseases associated with G-quadruplex-induced replication stress.Communications biology · 2026Review
- Illuminating Mitochondrial RNA G-Quadruplexes as Structural Brakes on RNA Granule Assembly and OXPHOS.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- G-quadruplex stabilization via small molecules as a potential anti-cancer strategy.Cellular & molecular biology letters · 2026Review
- Stability of non-canonical nucleic acid structure as a potential modulator of cell fate.Nucleic acids research · 2026Review
- Reversing uL3-mediated chemoresistance through synergistic combination of 5-FU and G-quadruplex ligands.NAR cancer · 2025Article
- G-quadruplex ligand RHPS4 compromises cellular radioresistance by inhibiting the mitochondrial adaptive response induced by ionizing irradiation.NAR cancer · 2025Article
- Ligase 3 prevents oxidative strand break-induced mitochondrial DNA loss but is not essential for replicative circularization.Nucleic acids research · 2025Article
- Vincristine Beyond Mitosis: Uncovering a First Link to G-Quadruplex DNA in Cancer Cells.International journal of molecular sciences · 2025Article
- Light-Activated Molecules Targeting G-Quadruplex Nucleic Acids.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Review
- The effect of prolonged G-quadruplex stabilization on the functions of human cells.Scientific reports · 2025Article
- Guanine quadruplexes mediate mitochondrial RNA polymerase pausing.BMC biology · 2025Article
- Predictability of environment-dependent formation of G-quadruplex DNAs in human mitochondria.Communications chemistry · 2025Article
- A DNP-Supported Solid-State NMR Approach to Study Nucleic Acids In Situ Reveals Berberine-Stabilized Hoogsteen Structures in Mitochondria.Angewandte Chemie (International ed. in English) · 2025Article
- Organelle-Specific Thiochromenocarbazole Imide Derivative as a Heavy-Atom-Free Type I Photosensitizer for Biomolecule-Triggered Image-Guided Photodynamic Therapy.The journal of physical chemistry letters · 2025Article
- DNA repair pathways in the mitochondria.DNA repair · 2025Review
- A subcellular selective APEX2-based proximity labeling used for identifying mitochondrial G-quadruplex DNA binding proteins.Nucleic acids research · 2025Article
- Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation.The Biochemical journal · 2024Review
- G-quadruplex propensity inNAR genomics and bioinformatics · 2024Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
Mitochondrial DNA (mtDNA) replication stalling is considered an initial step in the formation of mtDNA deletions that associate with genetic inherited disorders and aging. However, the molecular details of how stalled replication forks lead to mtDNA deletions accumulation are still unclear. Mitochondrial DNA deletion breakpoints preferentially occur at sequence motifs predicted to form G-quadruplexes (G4s), four-stranded nucleic acid structures that can fold in guanine-rich regions. Whether mtDNA G4s form in vivo and their potential implication for mtDNA instability is still under debate. In here, we developed new tools to map G4s in the mtDNA of living cells. We engineered a G4-binding protein targeted to the mitochondrial matrix of a human cell line and established the mtG4-ChIP method, enabling the determination of mtDNA G4s under different cellular conditions. Our results are indicative of transient mtDNA G4 formation in human cells. We demonstrate that mtDNA-specific replication stalling increases formation of G4s, particularly in the major arc. Moreover, elevated levels of G4 block the progression of the mtDNA replication fork and cause mtDNA loss. We conclude that stalling of the mtDNA replisome enhances mtDNA G4 occurrence, and that G4s not resolved in a timely manner can have a negative impact on mtDNA integrity.
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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.