ArticleNucleic acids research2013
Mitochondrial DNA replication proceeds via a 'bootlace' mechanism involving the incorporation of processed transcripts.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed.
- Structural and single-molecule insights into the core human mitochondrial DNA replisome.The Biochemical journal · 2026Review
- R-loops and D-loops: a delicate balance in genomic stability and instability.Cell communication and signaling : CCS · 2026Review
- Cryptic DNA sequences encode a temperature sensor to regulate mitochondrial suicide during neuronal differentiation.Cell communication and signaling : CCS · 2026Article
- Mitochondrial DNA replication is regulated by endoplasmic reticulum-mitochondrial contact sites, the mitochondrial calcium uniporter, and manganese.Nucleic acids research · 2026Article
- Human mitochondrial helicase Twinkle has RNA binding, annealing, and strand-exchange activities.Nucleic acids research · 2026Article
- TEFM facilitates transition from RNA synthesis to DNA synthesis at H-strand replication origin of mtDNA.Communications biology · 2025Article
- Technologies for Targeted RNA Degradation and Induced RNA Decay.Chemical reviews · 2024Review
- Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation.The Biochemical journal · 2024Review
- Light-strand bias and enriched zones of embedded ribonucleotides are associated with DNA replication and transcription in the human-mitochondrial genome.Nucleic acids research · 2024Article
- Mammalian DNA ligases; roles in maintaining genome integrity.Journal of molecular biology · 2024Review
- Genome-Wide Profiling of Endogenous Single-Stranded DNA Using the SSiNGLe-P1 Method.International journal of molecular sciences · 2023Article
- Dynamic Patterns of Mammalian Mitochondrial DNA Replication Uncovered Using SSiNGLe-5'ES.International journal of molecular sciences · 2023Article
- Mitochondrial DNA maintenance in Drosophila melanogaster.Bioscience reports · 2022Review
- Review
- Circulating Mitochondrial DNA and Inter-Organelle Contact Sites in Aging and Associated Conditions.Cells · 2022Review
- A rapid method to visualize human mitochondrial DNA replication through rotary shadowing and transmission electron microscopy.Nucleic acids research · 2021Article
- A replication-linked mutational gradient drives somatic mutation accumulation and influences germline polymorphisms and genome composition in mitochondrial DNA.Nucleic acids research · 2021Article
- Controlling the topology of mammalian mitochondrial DNA.Open biology · 2021Review
- DNA polymerase gamma mutations that impair holoenzyme stability cause catalytic subunit depletion.Nucleic acids research · 2021Article
- Extreme heterogeneity of human mitochondrial DNA from organelles to populations.Nature reviews. Genetics · 2021Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
The observation that long tracts of RNA are associated with replicating molecules of mitochondrial DNA (mtDNA) suggests that the mitochondrial genome of mammals is copied by an unorthodox mechanism. Here we show that these RNA-containing species are present in living cells and tissue, based on interstrand cross-linking. Using DNA synthesis in organello, we demonstrate that isolated mitochondria incorporate radiolabeled RNA precursors, as well as DNA precursors, into replicating DNA molecules. RNA-containing replication intermediates are chased into mature mtDNA, to which they are thus in precursor-product relationship. While a DNA chain terminator rapidly blocks the labeling of mitochondrial replication intermediates, an RNA chain terminator does not. Furthermore, processed L-strand transcripts can be recovered from gel-extracted mtDNA replication intermediates. Therefore, instead of concurrent DNA and RNA synthesis, respectively, on the leading and lagging strands, preformed processed RNA is incorporated as a provisional lagging strand during mtDNA replication. These findings indicate that RITOLS is a physiological mechanism of mtDNA replication, and that it involves a 'bootlace' mechanism, in which processed transcripts are successively hybridized to the lagging-strand template, as the replication fork advances.
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