DNA damage drives DNA methylation generation and evolution in plant [RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1128113 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29546156_1.fastq.gz | Fastqsanger.gz | |||
| SRR29546156_2.fastq.gz | Fastqsanger.gz | |||
| SRR29546157_1.fastq.gz | Fastqsanger.gz | |||
| SRR29546157_2.fastq.gz | Fastqsanger.gz | |||
| SRR29546158_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
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Project description:In mammals, it has long been hypothesized that DNA damage could induce DNA hypermethylation and contribute to carcinogenesis. However, the evidence that DNA damage is a cause of genome hypermethylation is still insufficient. Here, we demonstrated that, in plant, DNA damage can induce DNA hypermethylation in the context of symmetric CG, CHG as well as asymmetric CHH. Mechanically, DNA damage regulates the DREAM complex, to induce CG and CHG methylation. Moreover, DNA damage also utilizes the RdDM pathway to induce CHH hypermethylation. The hypermethylation sites of CG and CHG resulting from DNA damage tend to localize to gene body, and a large proportion of them are de nove generated. In contrast, the hypermethylation sites of CHH induced by DNA damage were mainly concentrated in the centromere and pre-centromere regions, and most of them are amplification of existing CHH methylation. Importantly, withdrawing the DNA damage or blocking the DNA damage response signal could fully abolish the CHH hypermethylation, partially rescue the CHG hypermethylation, but rarely recover the CG hypermethylation, indicating that DNA damage leaves symmetric DNA methylation as genetic imprinting. Collectively, our results suggest that DNA damage drives DNA methylation generation and evolution in plants.
2025-01-01 | GSE270750 | GEO
Project description:In mammals, it has long been hypothesized that DNA damage could induce DNA hypermethylation and contribute to carcinogenesis. However, the evidence that DNA damage is a cause of genome hypermethylation is still insufficient. Here, we demonstrated that, in plant, DNA damage can induce DNA hypermethylation in the context of symmetric CG, CHG as well as asymmetric CHH. Mechanically, DNA damage regulates the DREAM complex, to induce CG and CHG methylation. Moreover, DNA damage also utilizes the RdDM pathway to induce CHH hypermethylation. The hypermethylation sites of CG and CHG resulting from DNA damage tend to localize to gene body, and a large proportion of them are de nove generated. In contrast, the hypermethylation sites of CHH induced by DNA damage were mainly concentrated in the centromere and pre-centromere regions, and most of them are amplification of existing CHH methylation. Importantly, withdrawing the DNA damage or blocking the DNA damage response signal could fully abolish the CHH hypermethylation, partially rescue the CHG hypermethylation, but rarely recover the CG hypermethylation, indicating that DNA damage leaves symmetric DNA methylation as genetic imprinting. Collectively, our results suggest that DNA damage drives DNA methylation generation and evolution in plants.
2025-01-01 | GSE270747 | GEO
Project description:DNA damage drives DNA methylation generation and evolution in plant [BiSulfite-seq]
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Project description:Cellular senescence is a stress-induced permanent cell cycle arrest typically accompanied by expression of the cyclin-dependent kinase inhibitor p16. Recent studies have suggested that p16-expressing senescent cells accumulate in the body with age and play a causative role in aging. Various stresses, such as telomere shortening and oncogene activation, induce cellular senescence by generating DNA damage. However, how DNA damage leads to p16 expression is incompletely understood. We identified BNIP3 in a genome-wide siRNA screen for genes involved in p16 expression upon DNA damage. Mass spectrometric analysis of BNIP3-binding proteins yielded the DDR kinase ATM and components of the mitochondrial contact site and cristae organizing system (MICOS) complex. We found that BNIP3 increases the number of mitochondrial cristae upon DNA damage by electron microscopy. Metabolomic analysis linked BNIP3 to altered acetyl-CoA metabolism during DNA damage-induced senescence. We found that BNIP3 facilitates the oxidation of fatty acids to acetyl-CoA, an acetyl group donor, and promotes histone acetylation around the p16 gene and associated p16 expression. Our findings suggest that DDR signaling to mitochondria via BNIP3 promotes p16 expression through fatty acid oxidation and histone acetylation.
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Project description:The DNA damage response (DDR) acts as a barrier to malignant transformation and is often impaired during tumorigenesis. Exploiting the impaired DDR can be a promising therapeutic strategy; however, the mechanisms of inactivation and corresponding biomarkers are incompletely understood. Starting from an unbiased screening approach, we identified the SMC5-SMC6 Complex Localization Factor 2 (SLF2) as a regulator of the DDR and biomarker for a B-cell lymphoma (BCL) patient subgroup with an adverse prognosis. SLF2-deficiency leads to loss of DDR factors including CLSPN and consequently impairs CHK1 activation. In line with this mechanism, genetic deletion of Slf2 drives lymphomagenesis in vivo. Tumor cells lacking SLF2 are characterized by a high level of DNA damage, which leads to alterations of the post-translational SUMOylation pathway as a safeguard. The resulting co-dependency confers synthetic lethality to a clinically applicable SUMOylation inhibitor (SUMOi), and inhibitors of the DDR pathway act highly synergistic with SUMOi. Together, our results identify SLF2 as a DDR regulator and reveal co-targeting of the DDR and SUMOylation as a promising strategy for the treatment of aggressive lymphoma.
2023-07-21 | PXD041834 | Pride
Project description:The DNA damage response (DDR) acts as a barrier to malignant transformation and is often impaired during tumorigenesis. Exploiting the impaired DDR can be a promising therapeutic strategy; however, the mechanisms of inactivation and corresponding biomarkers are incompletely understood. Starting from an unbiased screening approach, we identified the SMC5-SMC6 Complex Localization Factor 2 (SLF2) as a regulator of the DDR and biomarker for a B-cell lymphoma (BCL) patient subgroup with an adverse prognosis. SLF2-deficiency leads to loss of DDR factors including CLSPN and consequently impairs CHK1 activation. In line with this mechanism, genetic deletion of Slf2 drives lymphomagenesis in vivo. Tumor cells lacking SLF2 are characterized by a high level of DNA damage, which leads to alterations of the post-translational SUMOylation pathway as a safeguard. The resulting co-dependency confers synthetic lethality to a clinically applicable SUMOylation inhibitor (SUMOi), and inhibitors of the DDR pathway act highly synergistic with SUMOi. Together, our results identify SLF2 as a DDR regulator and reveal co-targeting of the DDR and SUMOylation as a promising strategy for the treatment of aggressive lymphoma.
2023-07-21 | PXD041851 | Pride
Project description:Targetted metabolomics in U2OS PRDX1 WT and PRDX1-/- While cellular metabolism impacts the DNA damage response, a systematic understanding of the metabolic requirements that are crucial for DNA damage repair has yet to be achieved. Here, we investigate the metabolic enzymes and processes that are essential when cells are exposed to DNA damage. By integrating functional genomics with chromatin proteomics and metabolomics, we provide a detailed description of the interplay between cellular metabolism and the DNA damage response. Subsequent analysis identified Peroxiredoxin 1, PRDX1, as fundamental for DNA damage repair. During the DNA damage response, PRDX1 translocates to the nucleus where it is required to reduce DNA damage-induced nuclear reactive oxygen species levels. Moreover, PRDX1 controls aspartate availability, which is required for the DNA damage repair-induced upregulation of de novo nucleotide synthesis. Loss of PRDX1 leads to an impairment in the clearance of γΗ2ΑΧ nuclear foci, accumulation of replicative stress and cell proliferation defects, thus revealing a crucial role for PRDX1 as a DNA damage surveillance factor.
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