ArticleNucleic acids research2018
Flap endonuclease overexpression drives genome instability and DNA damage hypersensitivity in a PCNA-dependent manner.
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 32 papers.
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Who cites it
32 citing papers in PubMed, 46 citations in OpenAlex.
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- RNF4 and USP7 coordinate spatial regulation of SLX4 stability within the PML nuclear bodies.Nucleic acids research · 2025Article
- Prime Editing Modification with FEN1 Improves F508del Variant Editing in theInternational journal of molecular sciences · 2025Article
- Identification and evaluation of plasma exosome RNA biomarkers for non-invasive diagnosis of hepatocellular carcinoma using RNA-seq.BMC cancer · 2024Article
- Multifaceted roles of SUMO in DNA metabolism.Nucleus (Austin, Tex.) · 2024Review
- Effects of PCNA Stability on the Formation of Mutations.International journal of molecular sciences · 2024Article
- Article
- FEN1 Inhibition as a Potential Novel Targeted Therapy against Breast Cancer and the Prognostic Relevance of FEN1.International journal of molecular sciences · 2024Article
- FANCD2-dependent mitotic DNA synthesis relies on PCNA K164 ubiquitination.Cell reports · 2023Article
- Causal genetic regulation of DNA replication on immune microenvironment in colorectal tumorigenesis: Evidenced by an integrated approach of trans-omics and GWAS.Journal of biomedical research · 2023Article
- Elevated MSH2 MSH3 expression interferes with DNA metabolism in vivo.Nucleic acids research · 2023Article
- Explore the dominant factor in prime editing via a view of DNA processing.Synthetic and systems biotechnology · 2023Article
- Molecular Characterization of Esophageal Squamous Cell Carcinoma Using Quantitative Proteomics.Cancers · 2023Article
- Down-regulation of DNA key protein-FEN1 inhibits OSCC growth by affecting immunosuppressive phenotypes via IFN-γ/JAK/STAT-1.International journal of oral science · 2023Article
- Integrated agronomic, physiological, microstructure, and whole-transcriptome analyses reveal the role of biomass accumulation and quality formation during Se biofortification in alfalfa.Frontiers in plant science · 2023Article
- The landscape of aging.Science China. Life sciences · 2022Review
- Post-Translational Modifications of PCNA: Guiding for the Best DNA Damage Tolerance Choice.Journal of fungi (Basel, Switzerland) · 2022Review
- Integrative meta-analysis of gene expression profiles identifies FEN1 and ENDOU as potential diagnostic biomarkers for cervical squamous cell carcinoma.Oncology letters · 2021Article
- The prognostic significance of Flap Endonuclease 1 (FEN1) in breast ductal carcinoma in situ.Breast cancer research and treatment · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Overexpression of the flap endonuclease FEN1 has been observed in a variety of cancer types and is a marker for poor prognosis. To better understand the cellular consequences of FEN1 overexpression we utilized a model of its Saccharomyces cerevisiae homolog, RAD27. In this system, we discovered that flap endonuclease overexpression impedes replication fork progression and leads to an accumulation of cells in mid-S phase. This was accompanied by increased phosphorylation of the checkpoint kinase Rad53 and histone H2A-S129. RAD27 overexpressing cells were hypersensitive to treatment with DNA damaging agents, and defective in ubiquitinating the replication clamp proliferating cell nuclear antigen (PCNA) at lysine 164. These effects were reversed when the interaction between overexpressed Rad27 and PCNA was ablated, suggesting that the observed phenotypes were linked to problems in DNA replication. RAD27 overexpressing cells also exhibited an unexpected dependence on the SUMO ligases SIZ1 and MMS21 for viability. Importantly, we found that overexpression of FEN1 in human cells also led to phosphorylation of CHK1, CHK2, RPA32 and histone H2AX, all markers of genome instability. Our data indicate that flap endonuclease overexpression is a driver of genome instability in yeast and human cells that impairs DNA replication in a manner dependent on its interaction with PCNA.
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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.