ArticleFrontiers in genetics2015
R-loops and initiation of DNA replication in human cells: a missing link?
Article in Frontiers in genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 51 citations in OpenAlex.
- When R-Loops Go Awry: Genome Instability and Neurological Diseases.The European journal of neuroscience · 2026Review
- Specific origin selection and excess functional MCM2-7 loading in ORC-deficient cells.Nucleic acids research · 2025Article
- R-loops acted on by RNase H1 influence DNA replication timing and genome stability in Leishmania.Nature communications · 2025Article
- RAD51-mediated R-loop formation acts to repair transcription-associated DNA breaks driving antigenic variation inProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Immunoprecipitation of RNA-DNA hybrid interacting proteins in Trypanosoma brucei reveals conserved and novel activities, including in the control of surface antigen expression needed for immune evasion by antigenic variation.Nucleic acids research · 2023Article
- R-Loops in Genome Instability and Cancer.Cancers · 2023Review
- Review
- Recent Development in Biomedical Applications of Oligonucleotides with Triplex-Forming Ability.Polymers · 2023Review
- Review
- Recognition of ATT Triplex and DNA:RNA Hybrid Structures by Benzothiazole Ligands.Biomolecules · 2022Article
- Interplay of DNA and RNAPhysiology and molecular biology of plants : an international journal of functional plant biology · 2021Article
- Telomeres reforged with non-telomeric sequences in mouse embryonic stem cells.Nature communications · 2021Article
- G-quadruplex-R-loop interactions and the mechanism of anticancer G-quadruplex binders.Nucleic acids research · 2020Review
- Human cytomegalovirus long noncoding RNA4.9 regulates viral DNA replication.PLoS pathogens · 2020Article
- Trypanosoma brucei ribonuclease H2A is an essential R-loop processing enzyme whose loss causes DNA damage during transcription initiation and antigenic variation.Nucleic acids research · 2019Article
- Origins of DNA replication.PLoS genetics · 2019Review
- Non-canonical DNA/RNA structures during Transcription-Coupled Double-Strand Break Repair: Roadblocks or Bona fide repair intermediates?DNA repair · 2019Review
- The mitochondrial R-loop.Nucleic acids research · 2019Article
- Interactions between the transcription and replication machineries regulate the RNA and DNA synthesis in the herpesviruses.Virus genes · 2019Review
- Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The unanticipated widespread occurrence of stable hybrid DNA/RNA structures (R-loops) in human cells and the increasing evidence of their involvement in several human malignancies have invigorated the research on R-loop biology in recent years. Here we propose that physiological R-loop formation at CpG island promoters can contribute to DNA replication origin specification at these regions, the most efficient replication initiation sites in mammalian cells. Quite likely, this occurs by the strand-displacement reaction activating the formation of G-quadruplex structures that target the origin recognition complex (ORC) in the single-stranded conformation. In agreement with this, we found that R-loops co-localize with the ORC within the same CpG island region in a significant fraction of these efficient replication origins, precisely at the position displaying the highest density of G4 motifs. This scenario builds on the connection between transcription and replication in human cells and suggests that R-loop dysregulation at CpG island promoter-origins might contribute to the phenotype of DNA replication abnormalities and loss of genome integrity detected in cancer cells.
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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.