SCAI_Lschubert
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB52000 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR9454223_1.fastq.gz | Fastqsanger.gz | |||
| ERR9454223_2.fastq.gz | Fastqsanger.gz | |||
| ERR9454233_1.fastq.gz | Fastqsanger.gz | |||
| ERR9454233_2.fastq.gz | Fastqsanger.gz | |||
| ERR9454175_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:DNA replication is sensitive to damage in the template. To bypass lesions and complete replication, cells activate recombination-mediated (error-free) and translesion synthesis-mediated (error-prone) DNA damage tolerance pathways. Crucial for error-free DNA damage tolerance is template switching, which depends on the formation and resolution of damage-bypass intermediates consisting of sister chromatid junctions. Here we show that a chromatin architectural pathway involving the high mobility group box protein Hmo1 channels replication-associated lesions into the error-free DNA damage tolerance pathway mediated by Rad5 and PCNA polyubiquitylation, while preventing mutagenic bypass and toxic recombination. In the process of template switching, Hmo1 also promotes sister chromatid junction formation predominantly during replication. Its C-terminal tail, implicated in chromatin bending, facilitates the formation of catenations/hemicatenations and mediates the roles of Hmo1 in DNA damage tolerance pathway choice and sister chromatid junction formation. Together, the results suggest that replication-associated topological changes involving the molecular DNA bender, Hmo1, set the stage for dedicated repair reactions that limit errors during replication and impact on genome stability.
2014-01-28 | GSE46260 | GEO
Project description:DNA replication is sensitive to damage in the template. To bypass lesions and complete replication, cells activate recombination-mediated (error-free) and translesion synthesis-mediated (error-prone) DNA damage tolerance pathways. Crucial for error-free DNA damage tolerance is template switching, which depends on the formation and resolution of damage-bypass intermediates consisting of sister chromatid junctions. Here we show that a chromatin architectural pathway involving the high mobility group box protein Hmo1 channels replication-associated lesions into the error-free DNA damage tolerance pathway mediated by Rad5 and PCNA polyubiquitylation, while preventing mutagenic bypass and toxic recombination. In the process of template switching, Hmo1 also promotes sister chromatid junction formation predominantly during replication. Its C-terminal tail, implicated in chromatin bending, facilitates the formation of catenations/hemicatenations and mediates the roles of Hmo1 in DNA damage tolerance pathway choice and sister chromatid junction formation. Together, the results suggest that replication-associated topological changes involving the molecular DNA bender, Hmo1, set the stage for dedicated repair reactions that limit errors during replication and impact on genome stability. BrdU and proteins ChIP-chip analyses analysis were carried out as described (Bermejo et al., 2009). Labelled probes were hybridized to Affymetrix S.cerevisiae Tiling 1.0 (P/N 900645) arrays and processed with TAS software.
2014-01-28 | E-GEOD-46260 | biostudies-arrayexpress
Project description:The DNA damage inducible SOS response in bacteria serves to increase survival of the species. The SOS response first initiates error-free repair which is followed by error-prone repair. Here, we have employed a multi-omics approach to elucidate the temporal coordination of the SOS response using transcriptomics, signalomics, and metabolomics. Escherichia coli was grown in batch cultivation in bioreactors to ensure highly controlled conditions. Ciprofloxacin was used to induce the SOS response at a concentration that avoided extensive cell death. Our results show that expression of genes involved in error-free and error-prone repair were both induced shortly after DNA damage, thus, challenging the established perception that the expression of error-prone repair genes is delayed. By combining transcriptomics with signalomics, we found that temporal segregation of error-free and error-prone repair is primarily regulated after transcription. Furthermore, the heterology index was correlated to the maximum increase in gene expression and not to the time of induction of SOS genes. Finally, quantification of metabolites revealed an increase in pyrimidine pools as a late feature of the SOS response. Our results elucidate how the SOS response is coordinated, showing a rapid transcriptional response and temporal regulation of mutagenesis on the protein and metabolite levels.
2024-03-26 | GSE249682 | GEO
Project description:The DNA damage inducible SOS response in bacteria serves to increase survival of the species. The SOS response first initiates error-free repair which is followed by error-prone repair. Here, we have employed a multi-omics approach to elucidate the temporal coordination of the SOS response using transcriptomics, signalomics, and metabolomics. Escherichia coli was grown in batch cultivation in bioreactors to ensure highly controlled conditions, and a low dose of ciprofloxacin was used to activate the SOS response while avoiding extensive cell death. Our results show that expression of genes involved in error-free and error-prone repair were both induced shortly after DNA damage, thus, challenging the established perception that the expression of error-prone repair genes is delayed. By combining transcriptomics with signalomics, we found that temporal segregation of error-free and error-prone repair is primarily regulated after transcription. Furthermore, the heterology index was correlated to the maximum increase in gene expression and not to the time of induction of SOS genes. Finally, quantification of metabolites revealed increasing pyrimidine pools as a late feature of the SOS response. Our results elucidate how the SOS response is coordinated, showing a rapid transcriptional response and temporal regulation of mutagenesis on the protein and metabolite levels.
2024-03-26 | PXD047394 | Pride
Project description:Error-free and error-prone DNA repair gene expression through reprogramming and passage in human iPS cells
| PRJNA555421 | ENA
Project description:Secondary diversification of antibodies through somatic hypermutation (SHM) and class switch recombination (CSR) is a critical component of the immune response. Activation-induced deaminase (AID) initiates both processes by deaminating cytosine residues in immunoglobulin genes. The resulting U:G mismatch can be processed by alternative pathways to give rise to a mutation (SHM) or a DNA double-strand break (CSR). Central to this processing is the activity of uracil-N-glycosylase (UNG), an enzyme normally involved in error-free base excision repair. We used next generation sequencing to analyze the contribution of UNG to the resolution of AID-induced lesions. Loss- and gain-of-function experiments showed that UNG activity can promote both error-prone and high fidelity repair of U:G lesions. Unexpectedly, the balance between these alternative outcomes was influenced by the sequence context of the deaminated cytosine, with individual hotspots exhibiting higher susceptibility to UNG-triggered error-free or error-prone resolution. These results reveal UNG as a new molecular layer that shapes the specificity of AID-induced mutations and may provide new insights into the role of AID in cancer development.
2012-07-05 | GSE39114 | GEO
Project description:Secondary diversification of antibodies through somatic hypermutation (SHM) and class switch recombination (CSR) is a critical component of the immune response. Activation-induced deaminase (AID) initiates both processes by deaminating cytosine residues in immunoglobulin genes. The resulting U:G mismatch can be processed by alternative pathways to give rise to a mutation (SHM) or a DNA double-strand break (CSR). Central to this processing is the activity of uracil-N-glycosylase (UNG), an enzyme normally involved in error-free base excision repair. We used next generation sequencing to analyze the contribution of UNG to the resolution of AID-induced lesions. Loss- and gain-of-function experiments showed that UNG activity can promote both error-prone and high fidelity repair of U:G lesions. Unexpectedly, the balance between these alternative outcomes was influenced by the sequence context of the deaminated cytosine, with individual hotspots exhibiting higher susceptibility to UNG-triggered error-free or error-prone resolution. These results reveal UNG as a new molecular layer that shapes the specificity of AID-induced mutations and may provide new insights into the role of AID in cancer development.
2012-07-05 | GSE39108 | GEO
Project description:SPT6-driven error-free DNA repair safeguards genomic stability of glioblastoma cancer stem-like cells
| PRJNA516926 | ENA
Project description:Secondary diversification of antibodies through somatic hypermutation (SHM) and class switch recombination (CSR) is a critical component of the immune response. Activation-induced deaminase (AID) initiates both processes by deaminating cytosine residues in immunoglobulin genes. The resulting U:G mismatch can be processed by alternative pathways to give rise to a mutation (SHM) or a DNA double-strand break (CSR). Central to this processing is the activity of uracil-N-glycosylase (UNG), an enzyme normally involved in error-free base excision repair. We used next generation sequencing to analyze the contribution of UNG to the resolution of AID-induced lesions. Loss- and gain-of-function experiments showed that UNG activity can promote both error-prone and high fidelity repair of U:G lesions. Unexpectedly, the balance between these alternative outcomes was influenced by the sequence context of the deaminated cytosine, with individual hotspots exhibiting higher susceptibility to UNG-triggered error-free or error-prone resolution. These results reveal UNG as a new molecular layer that shapes the specificity of AID-induced mutations and may provide new insights into the role of AID in cancer development. Next Generation Sequencing analysis of mutations introduced by AID in activated B lymphocytes from WT and UNG-/- mice (n=4). Activated B cells from AID-/- mice (n=2) were used as negative controls.
2012-07-04 | E-GEOD-39114 | biostudies-arrayexpress
Project description:In response to DNA damage, cells arrest the cell cycle to repair damage, induce apoptosis when unrepaired, and avoid the accumulation of mutations. Our present analysis showed that oxidative stress causing DNA damage in the same condition resulted in apoptosis in induced pluripotent stem cells (iPSCs), but background levels of apoptosis in progenitor fibroblasts that just suffered cell-cycle arrest. PCA analysis of RNA-seq data and annexin V staining revealed apoptosis in iPSCs recovered within 24 hours. Characteristics as a stem cell obtained by reprogramming have shown that systems have been established that do not leave mutations in daughter cells by quickly induced apoptosis when accurate DNA repair was impossible. The surviving cells' gene expression reverts to approximately the same as that before oxidative damage in 24 hours, although the expression of error-free DNA repair-related genes has not reverted. On the other hand, the expression of error-prone polymerase POLH and REV3 revealed up-regulation. This pattern might cause the possibility of mutation in the genome after oxidative stress.
2019-10-01 | GSE138093 | GEO