ArticleThe Journal of biological chemistry2015
Flap Endonuclease 1 Limits Telomere Fragility on the Leading Strand.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Mechanistic insights into the monotherapy and combination potential of FEN1 inhibition in cancer therapy.Nucleic acids research · 2025Article
- Participants in Transcription-Replication Conflict and Their Role in Formation and Resolution of R-Loops.International journal of molecular sciences · 2025Review
- To cleave or not and how? The DNA exonucleases and endonucleases in immunity.Genes & diseases · 2025Review
- Article
- Role of Senataxin in Amyotrophic Lateral Sclerosis.Journal of molecular neuroscience : MN · 2023Review
- The THO complex counteracts TERRA R-loop-mediated telomere fragility in telomerase+ cells and telomeric recombination in ALT+ cells.Nucleic acids research · 2023Article
- Flap endonuclease Rad27 cleaves the RNA of R-loop structures to suppress telomere recombination.Nucleic acids research · 2023Article
- Review
- Article
- Flap Endonuclease 1 Endonucleolytically Processes RNA to Resolve R-Loops through DNA Base Excision Repair.Genes · 2022Article
- The Ultimate (Mis)match: When DNA Meets RNA.Cells · 2021Review
- ADAR1 RNA editing enzyme regulates R-loop formation and genome stability at telomeres in cancer cells.Nature communications · 2021Article
- Transcription-Replication Collisions and Chromosome Fragility.Frontiers in genetics · 2021Review
- Article
- Replication Stress at Telomeric and Mitochondrial DNA: Common Origins and Consequences on Ageing.International journal of molecular sciences · 2019Review
- Dual Processing of R-Loops and Topoisomerase I Induces Transcription-Dependent DNA Double-Strand Breaks.Cell reports · 2019Article
- SFPQ and NONO suppress RNA:DNA-hybrid-related telomere instability.Nature communications · 2019Article
- Review
- Structural basis of 5' flap recognition and protein-protein interactions of human flap endonuclease 1.Nucleic acids research · 2018Article
- Multifaceted Impact of MicroRNA 493-5p on Genome-Stabilizing Pathways Induces Platinum and PARP Inhibitor Resistance in BRCA2-Mutated Carcinomas.Cell reports · 2018Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The existence of redundant replication and repair systems that ensure genome stability underscores the importance of faithful DNA replication. Nowhere is this complexity more evident than in challenging DNA templates, including highly repetitive or transcribed sequences. Here, we demonstrate that flap endonuclease 1 (FEN1), a canonical lagging strand DNA replication protein, is required for normal, complete leading strand replication at telomeres. We find that the loss of FEN1 nuclease activity, but not DNA repair activities, results in leading strand-specific telomere fragility. Furthermore, we show that FEN1 depletion-induced telomere fragility is increased by RNA polymerase II inhibition and is rescued by ectopic RNase H1 expression. These data suggest that FEN1 limits leading strand-specific telomere fragility by processing RNA:DNA hybrid/flap intermediates that arise from co-directional collisions occurring between the replisome and RNA polymerase. Our data reveal the first molecular mechanism for leading strand-specific telomere fragility and the first known role for FEN1 in leading strand DNA replication. Because FEN1 mutations have been identified in human cancers, our findings raise the possibility that unresolved RNA:DNA hybrid structures contribute to the genomic instability associated with cancer.
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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.