ArticleCell research2011
Fen1 mutations that specifically disrupt its interaction with PCNA cause aneuploidy-associated cancer.
Article in Cell research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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
36 citing papers in PubMed, 54 citations in OpenAlex.
- From Adaptation to Collapse: Immune Remodeling, Mitochondrial Dysfunction, and Cell Death Induced by Polystyrene Nanoplastics in Procambarus clarkii Hepatopancreas.Marine biotechnology (New York, N.Y.) · 2026Article
- XPF mediates 3' flap processing for FEN1-independent Okazaki fragment maturation.Nucleic acids research · 2026Article
- PARP1-mediated 5' flap dynamics facilitate Okazaki fragment maturation.bioRxiv : the preprint server for biology · 2026Article
- Genetic Variants in BER Pathway Genes Confer Wilms Tumor Susceptibility: New Insights from an Eight-Center Case-Control Study in Chinese Children.Annals of surgical oncology · 2026Article
- XPF mediates 3' flap processing for FEN1-independent Okazaki fragment maturation.bioRxiv : the preprint server for biology · 2025Article
- 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
- Poly (ADP-Ribose) Glycohydrolase-Dependent dePARylation of PCNA Is Essential for DNA Replication.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Proteomics analysis reveals FEN1 as a promising therapeutic target against small cell neuroendocrine carcinoma of the cervix.Scientific reports · 2025Article
- Flap endonuclease-1 promotes pancreatic cancer progressionWorld journal of gastrointestinal oncology · 2025Article
- The flap endonuclease-1 promotes cellular tolerance to a chain-terminating nucleoside analog, alovudine, by counteracting the toxic effect of 53BP1.Nucleic acids research · 2025Article
- Polydopamine Powered Droplet Electricity Generator for Protein Assay with CRISPR/Cas Enabled Amplification.Nano letters · 2025Article
- Article
- Small-Molecule Inhibitors Targeting FEN1 for Cancer Therapy.Biomolecules · 2022Review
- Error-prone, stress-induced 3' flap-based Okazaki fragment maturation supports cell survival.Science (New York, N.Y.) · 2021Article
- Article
- Identification of a novel DNA repair-related prognostic signature predicting survival of patients with hepatocellular carcinoma.Cancer management and research · 2019Article
- SUMO-1 modification of FEN1 facilitates its interaction with Rad9-Rad1-Hus1 to counteract DNA replication stress.Journal of molecular cell biology · 2018Article
- Defect in phosphoinositide signalling through a homozygous variant inJournal of medical genetics · 2018Article
- Overexpression of Flap Endonuclease 1 Correlates with Enhanced Proliferation and Poor Prognosis of Non-Small-Cell Lung Cancer.The American journal of pathology · 2018Article
- Role of PCNA and RFC in promoting Mus81-complex activity.BMC biology · 2017Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
DNA replication and repair are critical processes for all living organisms to ensure faithful duplication and transmission of genetic information. Flap endonuclease 1 (Fen1), a structure-specific nuclease, plays an important role in multiple DNA metabolic pathways and maintenance of genome stability. Human FEN1 mutations that impair its exonuclease activity have been linked to cancer development. FEN1 interacts with multiple proteins, including proliferation cell nuclear antigen (PCNA), to form various functional complexes. Interactions with these proteins are considered to be the key molecular mechanisms mediating FEN1's key biological functions. The current challenge is to experimentally demonstrate the biological consequence of a specific interaction without compromising other functions of a desired protein. To address this issue, we established a mutant mouse model harboring a FEN1 point mutation (F343A/F344A, FFAA), which specifically abolishes the FEN1/PCNA interaction. We show that the FFAA mutation causes defects in RNA primer removal and long-patch base excision repair, even in the heterozygous state, resulting in numerous DNA breaks. These breaks activate the G2/M checkpoint protein, Chk1, and induce near-tetraploid aneuploidy, commonly observed in human cancer, consequently elevating the transformation frequency. Consistent with this, inhibition of aneuploidy formation by a Chk1 inhibitor significantly suppressed the cellular transformation. WT/FFAA FEN1 mutant mice develop aneuploidy-associated cancer at a high frequency. Thus, this study establishes an exemplary case for investigating the biological significance of protein-protein interactions by knock-in of a point mutation rather than knock-out of a whole gene.
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