ArticleNucleic acids research2018
Structural basis of 5' flap recognition and protein-protein interactions of human flap endonuclease 1.
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 12 papers.
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Who cites it
12 citing papers in PubMed, 11 citations in OpenAlex.
- Article
- JMJD1B-mediated FEN1 demethylation allows timely switching of Okazaki fragment maturation core enzymes to avoid mutagenic flap ligation by PARP1-LIG3.bioRxiv : the preprint server for biology · 2025Article
- CIAA: Integrated Proteomics and Structural Modeling for Understanding Cysteine Reactivity with Iodoacetamide Alkyne.ACS chemical biology · 2025Article
- TaqTth-hpRNA: a novel compact RNA-targeting tool for specific silencing of pathogenic mRNA.Genome biology · 2024Article
- Small-Molecule Inhibitors Targeting FEN1 for Cancer Therapy.Biomolecules · 2022Review
- miR-4324 inhibits ovarian cancer progression by targeting FEN1.Journal of ovarian research · 2022Article
- Biological and genomic characteristics of two bacteriophages isolated from sewage, using one multidrug-resistant and one non-multidrug-resistant strain ofFrontiers in microbiology · 2022Article
- A high-specificity flap probe-based isothermal nucleic acid amplification method based on recombinant FEN1-Bst DNA polymerase.Biosensors & bioelectronics · 2021Article
- Mouse papillomavirus type 1 (MmuPV1) DNA is frequently integrated in benign tumors by microhomology-mediated end-joining.PLoS pathogens · 2021Article
- Functional regulation of the structure-specific endonuclease FEN1 by the human cytomegalovirus protein IE1 suggests a role for the re-initiation of stalled viral replication forks.PLoS pathogens · 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
- Dynamic DNA-bound PCNA complexes co-ordinate Okazaki fragment synthesis, processing and ligation.Journal of molecular biology · 2020Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Human flap endonuclease 1 (hFEN1) is a structure-specific nuclease essential for DNA replication and repair processes. hFEN1 has 5' flap removal activity, as well as gap endonuclease activity that is critical for restarting stalled replication forks. Here, we report the crystal structures of wild-type and mutant hFEN1 proteins in complex with DNA substrates, followed by mutagenesis studies that provide mechanistic insight into the protein-protein interactions of hFEN1. We found that in an α-helix forming the helical gateway of hFEN1 recognizes the 5' flap prior to its threading into the active site for cleavage. We also found that the β-pin region is rigidified into a short helix in R192F hFEN1-DNA structures, suppressing its gap endonuclease activity and cycle-dependent kinase interactions. Our findings suggest that a single mutation at the primary methylation site can alter the function of hFEN1 and provide insight into the role of the β-pin region in hFEN1 protein interactions that are essential for DNA replication and repair.
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