ArticleNucleic acids research2022
Zebularine induces enzymatic DNA-protein crosslinks in 45S rDNA heterochromatin of Arabidopsis nuclei.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 17 citations in OpenAlex.
- The impact of DNA methyltransferase inhibitors on carotenoid metabolism in Dunaliella salina.Biotechnology letters · 2026Article
- Arabidopsis WSS1A, a DNA-protein crosslink repair protease, delays leaf senescence in cooperation with SUMO3.The Plant journal : for cell and molecular biology · 2026Article
- A novel programmed-cell-death-related prognostic risk model for cervical cancer based on mitochondrial genes.Translational cancer research · 2026Article
- Regulation of Pre-rRNA Processing in Plant: Mechanisms, Plasticity, and Developmental Implications.Plants (Basel, Switzerland) · 2026Review
- One-carbon metabolism in cancer: moonlighting functions of metabolic enzymes and anti-tumor therapy.Cancer metastasis reviews · 2025Review
- A Practical Approach to High-Throughput and Accurate Mapping-by-Sequencing in Arabidopsis.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Epigenetics of Chronic Stress: Mechanisms and Health Impacts.Current genomics · 2025Review
- The interplay of homology-directed repair pathways in the repair of zebularine-induced DNA-protein crosslinks in Arabidopsis.The Plant journal : for cell and molecular biology · 2024Article
- SMC5/6 complex-mediated SUMOylation stimulates DNA-protein cross-link repair in Arabidopsis.The Plant cell · 2023Article
- How Do Plants Cope with DNA Damage? A Concise Review on the DDR Pathway in Plants.International journal of molecular sciences · 2023Review
- Exploring the crop epigenome: a comparison of DNA methylation profiling techniques.Frontiers in plant science · 2023Review
- Revealing the transitory and local effect of zebularine on development and on proteome dynamics ofFrontiers in plant science · 2023Article
- Epigenetic Stress and Long-Read cDNA Sequencing of Sunflower (Plants (Basel, Switzerland) · 2022Article
- Analysis of BRCT5 domain-containing proteins reveals a new component of DNA damage repair in Arabidopsis.Frontiers in plant science · 2022Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Loss of genome stability leads to reduced fitness, fertility and a high mutation rate. Therefore, the genome is guarded by the pathways monitoring its integrity and neutralizing DNA lesions. To analyze the mechanism of DNA damage induction by cytidine analog zebularine, we performed a forward-directed suppressor genetic screen in the background of Arabidopsis thaliana zebularine-hypersensitive structural maintenance of chromosomes 6b (smc6b) mutant. We show that smc6b hypersensitivity was suppressed by the mutations in EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 3 (ENT3), DNA METHYLTRANSFERASE 1 (MET1) and DECREASE IN DNA METHYLATION 1 (DDM1). Superior resistance of ent3 plants to zebularine indicated that ENT3 is likely necessary for the import of the drug to the cells. Identification of MET1 and DDM1 suggested that zebularine induces DNA damage by interference with the maintenance of CG DNA methylation. The same holds for structurally similar compounds 5-azacytidine and 2-deoxy-5-azacytidine. Based on our genetic and biochemical data, we propose that zebularine induces enzymatic DNA-protein crosslinks (DPCs) of MET1 and zebularine-containing DNA in Arabidopsis, which was confirmed by native chromatin immunoprecipitation experiments. Moreover, zebularine-induced DPCs accumulate preferentially in 45S rDNA chromocenters in a DDM1-dependent manner. These findings open a new avenue for studying genome stability and DPC repair in plants.
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