DNA damage hotspots for the Top2i "ICRF193"
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1078073 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28009943_1.fastq.gz | Fastqsanger.gz | |||
| SRR28009943_2.fastq.gz | Fastqsanger.gz | |||
| SRR28009944_1.fastq.gz | Fastqsanger.gz | |||
| SRR28009944_2.fastq.gz | Fastqsanger.gz | |||
| SRR28009945_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
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Project description:We recently developed high-throughput sequencing approaches, eXcision Repair sequencing (XR-seq) and Damage-seq, to generate genome-wide mapping of DNA damage formation and excision repair, respectively, with single-nucleotide resolution. Here, we adopted time-course XR-seq data to profile UV-induced excision repair dynamics, paired with Damage-seq data to quantify the overall induced DNA damage. We identified genome-wide repair hotspots that are subject to exemplified amount of repair very soon after UV irradiation. We show that such repair hotspots do not result from hypersensitivity to DNA damage and are thus not damage hotspots. We find that the earliest repair occur preferentially in promoters and enhancers from open-chromatin regions. The repair hotspots are also significantly enriched for frequently interacting regions and super-enhancers, both of which are hotspots for local chromatin interactions. We further extend the interrogation of chromatin organization to DNA replication timing and conclude that early-repair hotspots are enriched for early-replication domains. Collectively, we report genome-wide early-repair hotspots of UV-induced damage, in association with chromatin states and epigenetic compartmentalization of the human genome.
2020-04-09 | GSE148303 | GEO
Project description:Purpose: The goal of this study is to profile and identify DNA damage hotspots that are sensitive to different replication stressors.
2019-06-24 | GSE113020 | GEO
Project description:In our project we are using the Top2 inhibitor, ICRF-193, in order to induce damage in NIH3T3 MEFs. We report the high-throughput identification of genomic hotspots for damage induction by ICRF-193, using γH2AX as a marker. We find that ICRF-193 primarily induces damage in repetitive sequences, which are known to reside in regions of heterochromatin, with a very small portion of damaged sites residing in regions of active genes in euchromatin. Overall, this study provides evidence that catalytic inhibition of Top2 enzymes by ICRF-193, leads to induction of damage in the nuclear sub-compartments of heterochromatin.
2024-04-17 | GSE256090 | GEO
Project description:In human leukemia, lineage-specific genes represent predominant targets of deletion, with lymphoid-specific genes frequently affected in lymphoid leukemia and myeloid-specific genes in myeloid leukemia. To investigate the basis of lineage-specific alterations, we analyzed global DNA damage in primary B-cell precursors expressing leukemia-inducing oncogenes by ChIP-Seq. We identified >1000 sensitive regions, of which B-lineage-specific genes constitute the most prominent targets. Identified hotspots at B-lineage genes relate to DNA-DSBs, affect genes that harbor genomic lesions in human leukemia, and associate with ectopic deletion in successfully transformed cells. We further show that most identified regions overlap with gene bodies of highly expressed genes, and that induction of a myeloid lineage phenotype in transformed B-cell precursors promotes de novo DNA damage at myeloid loci. Hence, we demonstrate that lineage-specific transcription predisposes lineage-specific genes in transformed B-cell precursors to DNA damage, which is likely to promote the frequent alteration of lineage-specific genes in human leukemia.
2017-02-13 | GSE80682 | GEO
Project description:Excision repair hotspots of UV-induced DNA damage in the human genome
| PRJNA623860 | ENA
Project description:Genome-wide mapping of DNA damage hotspots in response to various replication stressors
| PRJNA449770 | ENA
Project description:Single strand breaks (SSBs) represent one of the most common types of DNA damage yet not much is known about the genome landscapes of this type of DNA lesions in mammalian cells. Here, we found that SSBs are more likely to occur in certain positions of the human genome — SSB hotspots — in different cells of the same cell type and in different cell types. We hypothesize that the hotspots are likely to represent biologically relevant breaks. And, we found that the hotspots had a prominent tendency to be enriched in the immediate vicinity of transcriptional start sites (TSSs). We show that these hotspots are not likely to represent technical artifacts, or be caused by common mechanisms previously found to cause DNA cleavage at promoters, such as apoptotic DNA fragmentation or topoisomerase type II (TOP2) activity. Therefore, such TSS-associated hotspots could potentially be generated using a novel mechanism, that could involve preferential cleavage at cytosines, and their existence is consistent with recent studies suggesting a complex relationship between DNA damage and regulation of gene expression.
2022-08-18 | GSE190735 | GEO
Project description:Meiotic recombination, crucial for proper chromosome segregation and genome evolution, is initiated by programmed DNA double-strand breaks (DSBs) in budding and fission yeasts and likely all sexually reproducing species. In fission yeast, DSBs occur up to several hundred times more frequently at special sites, called hotspots, than in other regions of the genome. What distinguishes hotspots from cold regions is a major unsolved problem, although transcription factors determine some hotspots. We report here the discovery that three coiled-coil proteins -- Rec25, Rec27, and Mug20 -- bind essentially all hotspots with unprecedented, high specificity even without DSB formation. These small proteins are components of linear elements, are related to synaptonemal complex proteins, and are essential for nearly all DSBs at most hotspots. Our results indicate that these hotspot determinants activate or stabilize the DSB-forming protein Rec12 (Spo11 homolog) rather than promote its binding to hotspots. We propose here a new paradigm for hotspot determination and crossover control by linear element proteins.
2012-12-26 | GSE43121 | GEO
Project description:Meiotic recombination, crucial for proper chromosome segregation and genome evolution, is initiated by programmed DNA double-strand breaks (DSBs) in budding and fission yeasts and likely all sexually reproducing species. In fission yeast, DSBs occur up to several hundred times more frequently at special sites, called hotspots, than in other regions of the genome. What distinguishes hotspots from cold regions is a major unsolved problem, although transcription factors determine some hotspots. We report here the discovery that three coiled-coil proteins -- Rec25, Rec27, and Mug20 -- bind essentially all hotspots with unprecedented, high specificity even without DSB formation. These small proteins are components of linear elements, are related to synaptonemal complex proteins, and are essential for nearly all DSBs at most hotspots. Our results indicate that these hotspot determinants activate or stabilize the DSB-forming protein Rec12 (Spo11 homolog) rather than promote its binding to hotspots. We propose here a new paradigm for hotspot determination and crossover control by linear element proteins.
2012-12-26 | GSE43118 | GEO
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.
2022-07-19 | ST002234 | MetabolomicsWorkbench