ArticleThe EMBO journal2015
Okazaki fragment maturation involves α-segment error editing by the mammalian FEN1/MutSα functional complex.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Redundant mispair excision mechanisms in eukaryotic DNA mismatch repair.Nucleus (Austin, Tex.) · 2026Review
- Replication associated nuclear DNA mismatch repair across kingdoms.Biochemical Society transactions · 2026Review
- XPF mediates 3' flap processing for FEN1-independent Okazaki fragment maturation.Nucleic acids research · 2026Article
- XPF mediates 3' flap processing for FEN1-independent Okazaki fragment maturation.bioRxiv : the preprint server for biology · 2025Article
- EGFR-mediated HSP70 phosphorylation facilitates PCNA association with chromatin and DNA replication.Nucleic acids research · 2024Article
- Human DNA polymerase α has a strong mutagenic potential at the initial steps of DNA synthesis.Nucleic acids research · 2022Article
- Mechanistic investigation of human maturation of Okazaki fragments reveals slow kinetics.Nature communications · 2022Article
- FEN1 inhibitor synergizes with low-dose camptothecin to induce increased cell killing via the mitochondria mediated apoptotic pathway.Gene therapy · 2022Article
- The nuclease activity of DNA2 promotes exonuclease 1-independent mismatch repair.The Journal of biological chemistry · 2022Article
- Error-prone, stress-induced 3' flap-based Okazaki fragment maturation supports cell survival.Science (New York, N.Y.) · 2021Article
- Rad27 and Exo1 function in different excision pathways for mismatch repair in Saccharomyces cerevisiae.Nature communications · 2021Article
- Strand discrimination in DNA mismatch repair.DNA repair · 2021Review
- FEN1 inhibitor increases sensitivity of radiotherapy in cervical cancer cells.Cancer medicine · 2019Article
- SUMO-1 modification of FEN1 facilitates its interaction with Rad9-Rad1-Hus1 to counteract DNA replication stress.Journal of molecular cell biology · 2018Article
- Phosphate steering by Flap Endonuclease 1 promotes 5'-flap specificity and incision to prevent genome instability.Nature communications · 2017Article
- FEN1 promotes tumor progression and confers cisplatin resistance in non-small-cell lung cancer.Molecular oncology · 2017Article
- Direct Visualization of RNA-DNA Primer Removal from Okazaki Fragments Provides Support for Flap Cleavage and Exonucleolytic Pathways in Eukaryotic Cells.The Journal of biological chemistry · 2017Article
- Role of FEN1 S187 phosphorylation in counteracting oxygen-induced stress and regulating postnatal heart development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Article
- Eukaryotic genome instability in light of asymmetric DNA replication.Critical reviews in biochemistry and molecular biology · 2016Review
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14 authors at 6 institutions in 2 countries.
Funding
Abstract
During nuclear DNA replication, proofreading-deficient DNA polymerase α (Pol α) initiates Okazaki fragment synthesis with lower fidelity than bulk replication by proofreading-proficient Pol δ or Pol ε. Here, we provide evidence that the exonuclease activity of mammalian flap endonuclease (FEN1) excises Pol α replication errors in a MutSα-dependent, MutLα-independent mismatch repair process we call Pol α-segment error editing (AEE). We show that MSH2 interacts with FEN1 and facilitates its nuclease activity to remove mismatches near the 5' ends of DNA substrates. Mouse cells and mice encoding FEN1 mutations display AEE deficiency, a strong mutator phenotype, enhanced cellular transformation, and increased cancer susceptibility. The results identify a novel role for FEN1 in a specialized mismatch repair pathway and a new cancer etiological mechanism.
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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.