ArticleeLife2017
Single-molecule FRET unveils induced-fit mechanism for substrate selectivity in flap endonuclease 1.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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.
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Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
- Dual and opposing roles of the EXD2 exonuclease in the resolution of RNA-DNA hybrids.Nucleic acids research · 2026Article
- Functional roles for FEN1 phosphate steering residues in multi-step substrate verification prior to reaction.The Journal of biological chemistry · 2026Article
- DNA polymerase I: structure, activity, and function in bacterial DNA replication and repair.Critical reviews in biochemistry and molecular biology · 2026Review
- Single-molecule studies of repair proteins in base excision repair.BMB reports · 2025Review
- Nuclease-induced stepwise photodropping (NISP) to precisely investigate single-stranded DNA degradation behaviors of exonucleases and endonucleases.Nucleic acids research · 2024Article
- Molecular architecture and functional dynamics of the pre-incision complex in nucleotide excision repair.Nature communications · 2024Article
- Single-Molecule Imaging of Integral Membrane Protein Dynamics and Function.Annual review of biophysics · 2024Review
- A scanning-to-incision switch in TFIIH-XPG induced by DNA damage licenses nucleotide excision repair.Nucleic acids research · 2023Article
- Mechanistic investigation of human maturation of Okazaki fragments reveals slow kinetics.Nature communications · 2022Article
- Structural dynamics of DNA strand break sensing by PARP-1 at a single-molecule level.Nature communications · 2022Article
- Universally Accessible Structural Data on Macromolecular Conformation, Assembly, and Dynamics by Small Angle X-Ray Scattering for DNA Repair Insights.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Visualizing functional dynamicity in the DNA-dependent protein kinase holoenzyme DNA-PK complex by integrating SAXS with cryo-EM.Progress in biophysics and molecular biology · 2021Article
- EXO5-DNA structure and BLM interactions direct DNA resection critical for ATR-dependent replication restart.Molecular cell · 2021Article
- Implementing fluorescence enhancement, quenching, and FRET for investigating flap endonuclease 1 enzymatic reaction at the single-molecule level.Computational and structural biotechnology journal · 2021Review
- Decoding Cancer Variants of Unknown Significance for Helicase-Nuclease-RPA Complexes Orchestrating DNA Repair During Transcription and Replication.Frontiers in molecular biosciences · 2021Article
- Dynamic DNA-bound PCNA complexes co-ordinate Okazaki fragment synthesis, processing and ligation.Journal of molecular biology · 2020Article
- Jianpi-yangwei decoction inhibits DNA damage repair in the drug resistance of gastric cancer by reducing FEN1 expression.BMC complementary medicine and therapies · 2020Article
- Human XPG nuclease structure, assembly, and activities with insights for neurodegeneration and cancer from pathogenic mutations.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Structure of the processive human Pol δ holoenzyme.Nature communications · 2020Article
- Initial state of DNA-Dye complex sets the stage for protein induced fluorescence modulation.Nature communications · 2019Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Human flap endonuclease 1 (FEN1) and related structure-specific 5'nucleases precisely identify and incise aberrant DNA structures during replication, repair and recombination to avoid genomic instability. Yet, it is unclear how the 5'nuclease mechanisms of DNA distortion and protein ordering robustly mediate efficient and accurate substrate recognition and catalytic selectivity. Here, single-molecule sub-millisecond and millisecond analyses of FEN1 reveal a protein-DNA induced-fit mechanism that efficiently verifies substrate and suppresses off-target cleavage. FEN1 sculpts DNA with diffusion-limited kinetics to test DNA substrate. This DNA distortion mutually 'locks' protein and DNA conformation and enables substrate verification with extreme precision. Strikingly, FEN1 never misses cleavage of its cognate substrate while blocking probable formation of catalytically competent interactions with noncognate substrates and fostering their pre-incision dissociation. These findings establish FEN1 has practically perfect precision and that separate control of induced-fit substrate recognition sets up the catalytic selectivity of the nuclease active site for genome stability.
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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.