ArticleNucleic acids research2018
A two-nuclease pathway involving RNase H1 is required for primer removal at human mitochondrial OriL.
Article in Nucleic acids research, 2018. 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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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Mitochondrial DNA Replication and Disease: A Historical Perspective on Molecular Insights and Therapeutic Advances.International journal of molecular sciences · 2025Review
- Mechanism of RNA primer removal in plastid DNA replication.Nature plants · 2025Article
- R-loop control and mitochondrial genome stability require the 5'-3' exonuclease/flap endonuclease OEX1.The Plant cell · 2025Article
- Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation.The Biochemical journal · 2024Review
- Structural basis of how MGME1 processes DNA 5' ends to maintain mitochondrial genome integrity.Nucleic acids research · 2024Article
- PARP1 associates with R-loops to promote their resolution and genome stability.Nucleic acids research · 2023Article
- Mechanism of strand displacement DNA synthesis by the coordinated activities of human mitochondrial DNA polymerase and SSB.Nucleic acids research · 2023Article
- Structural and Molecular Basis for Mitochondrial DNA Replication and Transcription in Health and Antiviral Drug Toxicity.Molecules (Basel, Switzerland) · 2023Review
- In vitro reconstitution reveals a key role of human mitochondrial EXOG in RNA primer processing.Nucleic acids research · 2022Article
- How RNases Shape Mitochondrial Transcriptomes.International journal of molecular sciences · 2022Review
- Pivotal role of a conserved histidine in Escherichia coli ribonuclease HI as proposed by X-ray crystallography.Acta crystallographica. Section D, Structural biology · 2022Article
- Mitochondrial RNase H1 activity regulates R-loop homeostasis to maintain genome integrity and enable early embryogenesis in Arabidopsis.PLoS biology · 2021Article
- DNA polymerase gamma mutations that impair holoenzyme stability cause catalytic subunit depletion.Nucleic acids research · 2021Article
- The Maintenance of Mitochondrial DNA Integrity and Dynamics by Mitochondrial Membranes.Life (Basel, Switzerland) · 2020Review
- Structure-Function Analysis Reveals the Singularity of Plant Mitochondrial DNA Replication Components: A Mosaic and Redundant System.Plants (Basel, Switzerland) · 2019Review
- A unique exonuclease ExoG cleaves between RNA and DNA in mitochondrial DNA replication.Nucleic acids research · 2019Article
- RNase H1 Regulates Mitochondrial Transcription and TranslationFrontiers in genetics · 2019Article
- Identification and Characterization of NewFrontiers in genetics · 2019Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The role of Ribonuclease H1 (RNase H1) during primer removal and ligation at the mitochondrial origin of light-strand DNA synthesis (OriL) is a key, yet poorly understood, step in mitochondrial DNA maintenance. Here, we reconstitute the replication cycle of L-strand synthesis in vitro using recombinant mitochondrial proteins and model OriL substrates. The process begins with initiation of DNA replication at OriL and ends with primer removal and ligation. We find that RNase H1 partially removes the primer, leaving behind the last one to three ribonucleotides. These 5'-end ribonucleotides disturb ligation, a conclusion which is supported by analysis of RNase H1-deficient patient cells. A second nuclease is therefore required to remove the last ribonucleotides and we demonstrate that Flap endonuclease 1 (FEN1) can execute this function in vitro. Removal of RNA primers at OriL thus depends on a two-nuclease model, which in addition to RNase H1 requires FEN1 or a FEN1-like activity. These findings define the role of RNase H1 at OriL and help to explain the pathogenic consequences of disease causing mutations in RNase H1.
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