ArticleNucleic acids research2020
Benzo[a]pyrene represses DNA repair through altered E2F1/E2F4 function marking an early event in DNA damage-induced cellular senescence.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Broad repression of DNA repair genes in senescent cells identified by integration of transcriptomic data.Nucleic acids research · 2025Pooled it
- Replication associated nuclear DNA mismatch repair across kingdoms.Biochemical Society transactions · 2026Review
- From Food Contaminant to Therapeutic Target: Identification of KCNE2 and 5-Azacytidine for Gastric Cancer via Multi-Omics, Machine Learning, and In Vitro Validation.Pharmaceuticals (Basel, Switzerland) · 2026Article
- PMM2 interacts with TRIM28 to recruit E2F4 and promote KIFC3-mediated tumor glycolysis and colorectal cancer progression.Oncogene · 2026Article
- Cellular Senescence Triggered by Food and Environmental Genotoxins.International journal of molecular sciences · 2026Review
- Effects of Aerosol Extract From Heated Tobacco Products on Senescence-Associated Gene Expression in Human Lung Fibroblasts.Geriatrics & gerontology international · 2026Article
- Research on plant knowledge graph reasoning based on dual-channel attention and topological perception.Frontiers in plant science · 2026Article
- Metabolic Responses to Cyclic Fasting in Juvenile Turbot (Aquaculture nutrition · 2026Article
- OFD1 inhibition induces BRCAness to create a therapeutic vulnerability to PARP inhibition in pancreatic cancer.Nature communications · 2025Article
- A Comprehensive Analysis of the Role of PAX9 in Head and Neck Squamous Cell Carcinoma.Current molecular medicine · 2025Article
- Bio-Inspired Polymeric Solid Lipid Nanoparticles for siRNA Delivery: Cytotoxicity and Cellular Uptake In Vitro.Polymers · 2024Article
- Ginkgo Biloba Extract Can Antagonize Subchronic Arsenite Exposure-Induced Hepatocyte Senescence by Inhibiting Oxidative Damage and Inflammation in Rats.Biological trace element research · 2024Article
- The p21CIP1-CDK4-DREAM axis is a master regulator of genotoxic stress-induced cellular senescence.Nucleic acids research · 2024Article
- Wemics: A Single-Base Resolution Methylation Quantification Method for Enhanced Prediction of Epigenetic Regulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Clinical evidence for a role of E2F1-induced replication stress in modulating tumor mutational burden and immune microenvironment.DNA repair · 2023Article
- FOLR1-induced folate deficiency reduces viral replication via modulating APOBEC3 family expression.Virologica Sinica · 2023Article
- Involvement and targeted intervention of benzo(a)pyrene-regulated apoptosis related proteome modification and muti-drug resistance in hepatocellular carcinoma.Cell death & disease · 2023Article
- Article
- Understanding the Impact of Obesity on Ageing in the Radiance of DNA Metabolism.The journal of nutrition, health & aging · 2023Review
- E2F4DN Transgenic Mice: A Tool for the Evaluation of E2F4 as a Therapeutic Target in Neuropathology and Brain Aging.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcriptional regulation of DNA repair is of outmost importance for the restoration of DNA integrity upon genotoxic stress. Here we report that the potent environmental carcinogen benzo[a]pyrene (B[a]P) activates a cellular DNA damage response resulting in transcriptional repression of mismatch repair (MMR) genes (MSH2, MSH6, EXO1) and of RAD51, the central homologous recombination repair (HR) component, ultimately leading to downregulation of MMR and HR. B[a]P-induced gene repression is caused by abrogated E2F1 signalling. This occurs through proteasomal degradation of E2F1 in G2-arrested cells and downregulation of E2F1 mRNA expression in G1-arrested cells. Repression of E2F1-mediated transcription and silencing of repair genes is further mediated by the p21-dependent E2F4/DREAM complex. Notably, repression of DNA repair is also observed following exposure to the active B[a]P metabolite BPDE and upon ionizing radiation and occurs in response to a p53/p21-triggered, irreversible cell cycle arrest marking the onset of cellular senescence. Overall, our results suggest that repression of MMR and HR is an early event during genotoxic-stress induced senescence. We propose that persistent downregulation of DNA repair might play a role in the maintenance of the senescence phenotype, which is associated with an accumulation of unrepairable DNA lesions.
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