Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The multiscale distribution of radiation-induced DNA damage and its impact on local genome structure

ABSTRACT: The three-dimensional genome structure is critical for the regulation of gene expression and repair of DNA damage. While previous work has characterized genome-wide sites of DNA damage caused by etoposide or nucleases, the distribution of double-strand breaks (DSBs) caused by external radiation and how these interact with the 3D genome organization is less well understood. Here, we measure the genomic landscape of radiation-induced DNA damage using END-seq in fibroblasts and lymphoblasts after exposure to 5 Gy X-rays. We identify frequently broken regions and investigate the 3D genome properties around these breaks with Hi-C data. We observe that the distribution of robust breaks correlates with transcriptional and chromatin features of the genome. Transcriptionally active and decondensed regions, such as chromosome 19, the A compartment, and topologically associating domain (TAD) boundaries, show pronounced break probability. We also find evidence of DSB-induced loop formation in the vicinity of frequent radiation-induced breaks. Our data reveal that pre-existing 3D genome architecture influences the distribution of radiation-induced DSBs and that these breaks reshape local chromatin landscapes, advancing our understanding of genome instability.

ORGANISM(S): Homo sapiens

PROVIDER: GSE306338 | GEO | 2025/08/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

ChIP-Seq mapping of histone modifications at multiple DNA Double Strand Breaks

Project description:DNA Double Strands Breaks (DSBs) are highly detrimental since they can lead to mutations and chromosomes rearrangements (amplification, deletion, translocation and chromosome loss). Here, we used in a standardized system, where multiples DSBs are induced at defined positions across the human genome (U2OS-DIvA cells), to describe the distribution of eighteen histone modifications before and after damage using ChIP-Seq. This provides a comprehensive picture of the chromatin landscape induced at DSBs.

2018-09-27 | E-MTAB-5817 | biostudies-arrayexpress

Expression data for program activation by IR-induced DNA breaks in G1 phase Murine PreB cells

Project description:The objective of this set of samples is to identify genes that are differentially expressed following the introduction of DNA double strand breaks (DSBs) by ionizing radiation in wild-type murine pre-B cells. The data generated in this project will be compared to the data generated in GSE9024, in which genes that are differentially expressed following the introduction of DNA double strand breaks (DSBs) by the Rag proteins in murine pre-B cells were examined. In order to understand the differences between the physiologic and genotoxic responses to DSB DNA damage, we need to compare cells that are all in the same compartment of the cell cycle. We are therefore examining the response to IR-induced damage in cells that are arrested in G1, which would correspond to our previous study of G1 arrested cells with Rag-induced breaks. This will illuminate the difference directly, allowing us to better understand the signaling responses to the different types of DNA damage. Murine v-abl-transformed pre-B cells were treated with 3 uM STI571 for 48 hours. The cell type is Wild type (3 biological replicates). For each wild type cell line, cells were treated with 1 Gy ionizing radiation or no ionizing radiation. Each sample was hybridized once using Affymetrix Mouse Genome 2.0 GeneChip arrays (Mouse 430 v2, Affymetrix, Santa Clara, CA). Data were analyzed using the unirradiated samples as the controls.

2013-03-13 | E-GEOD-36530 | biostudies-arrayexpress

Genome-wide mapping of early replication fragile sites (ERFS)

Project description:DNA double strand breaks (DSBs) in B lymphocytes are thought to arise stochastically during replication (S phase) or as a result of targeted DNA damage by activation induced cytidine deaminase (AID) in G1. Here we identify a novel class of recurrent, early replicating and AID independent DNA lesions, termed early replication fragile sites (ERFS), by genome-wide localization of DNA repair proteins DNA double strand breaks (DSBs) in B lymphocytes are thought to arise stochastically during replication (S phase) or as a result of targeted DNA damage by activation induced cytidine deaminase (AID) in G1. Here we identify a novel class of recurrent, early replicating and AID independent DNA lesions, termed early replication fragile sites (ERFS), by genome-wide localization of DNA repair proteins DNA double strand breaks (DSBs) in B lymphocytes are thought to arise stochastically during replication (S phase) or as a result of targeted DNA damage by activation induced cytidine deaminase (AID) in G1. Here we identify a novel class of recurrent, early replicating and AID independent DNA lesions, termed early replication fragile sites (ERFS), by genome-wide localization of DNA repair proteins RPA, SMC5, gamma-H2AX, and BRCA1 in B cells subjected to replication stress. Protein-DNA association for four DNA damage response proteins (RPA, SMC5, g-H2AX, BRCA1), BrdU incorporation, and gene transcription in B lymphocytes with and without hydroxyurea treatment were examined.

2013-02-04 | E-GEOD-43504 | biostudies-arrayexpress

Ma2005-digital response of p53 to DNA damage-ATM Activation Module

Project description:Recent observations show that the single-cell response of p53 to ionizing radiation (IR) is “digital” in that it is the number of oscillations rather than the amplitude of p53 that shows dependence on the radiation dose. We present a model of this phenomenon. In our model, double-strand break (DSB) sites induced by IR interact with a limiting pool of DNA repair proteins, forming DSB–protein complexes at DNA damage foci. The persisting complexes are sensed by ataxia telangiectasia mutated (ATM), a protein kinase that activates p53 once it is phosphorylated by DNA damage. The ATM-sensing module switches on or off the downstream p53 oscillator, consisting of a feedback loop formed by p53 and its negative regulator, Mdm2. In agreement with experiments, our simulations show that by assuming stochasticity in the initial number of DSBs and the DNA repair process, p53 and Mdm2 exhibit a coordinated oscillatory dynamics upon IR stimulation in single cells, with a stochastic number of oscillations whose mean increases with IR dose. The damped oscillations previously observed in cell populations can be explained as the aggregate behavior of single cell

2020-05-13 | MODEL2005130001 | BioModels

Expression data for program activation by IR-induced DNA breaks in G1 phase Murine PreB cells

2013-03-13 | GSE36530 | GEO

Genome-wide mapping of early replication fragile sites (ERFS)

2013-02-04 | GSE43504 | GEO

Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration [Hi-C]

Project description:Persistent DNA double-strand breaks (DSBs) in neurons are an early pathological hallmark of neurodegenerative diseases including Alzheimer’s Disease (AD), with the potential to disrupt genome integrity. We used single-nucleus RNA-seq in human post-mortem prefrontal cortex samples and found that excitatory neurons in AD were enriched for somatic mosaic gene fusions. Gene fusions were particularly enriched in excitatory neurons with DNA damage repair and senescence gene signatures. In addition, somatic genome structural variations and gene fusions were enriched in neurons burdened with DSBs in the CK-p25 mouse model of neurodegeneration. Neurons enriched for DSBs also had elevated levels of cohesin along with progressive multiscale disruption of the 3D genome organization aligned with transcriptional changes in synaptic, neuronal development, and histone genes. Overall, this study demonstrates the disruption of genome stability and the 3D genome organization by DSBs in neurons as pathological steps in the progression of neurodegenerative diseases.

2023-09-27 | GSE227443 | GEO

Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration [BLISS]

2023-09-27 | GSE227438 | GEO

Mechanism for local attenuation of DNA replication at double-strand breaks

Project description:DNA double-strand breaks (DSBs) destroy the continuity of our genome with consequences for malignant transformation. Massive DNA damage can elicit a cellular checkpoint response that prevents cell proliferation. However, how highly aggressive cancer cells, which can tolerate widespread DNA damage, respond to DSBs alongside continuous chromosome duplication is unknown. Here we show that DSBs induce a local, hitherto unreported genome maintenance mechanism that inhibits replication initiation in DSB-containing topologically associating domains (TADs) without affecting DNA synthesis at other genomic locations. This process is facilitated by Mediators of Replication and DSBs (MRDs). In normal and cancer cells, MRDs include the TIMELESS-TIPIN complex and the WEE1 kinase, which actively dislodges the TIMELESS-TIPIN complex from replication origins adjacent to DSBs and prevents initiation of DNA synthesis at DSB-containing TADs. Dysregulation of MRDs, or disruption of 3D chromatin architecture by dissolving TADs, results in inadvertent replication in damaged chromatin and increased DNA damage in cancer cells. We propose that the intact MRD cascade precedes DSB repair to prevent genomic instability, which is otherwise observed when replication is forced, or when genome architecture is challenged, in the presence of DSBs. These observations reveal a previously undiscovered vulnerability in the DNA replication machinery that may be exploited to therapeutically target cancer cells.

2025-02-19 | GSE254206 | GEO

Multi-Dimensional Epigenetic Analysis Reveals Transcription as a Primary Driver of Radiation Induced Double Strand Break Recognition

Project description:DNA Double Strand Breaks (DSBs) are a deleterious product of genotoxic agents or radiotherapy. Despite the inherent chromatin localization of DSBs, the literature has largely ignored the effect of local chromatin or histone post translational modifications (PTMs) on DSB induction or recognition especially in a therapy-relevant setting. Analysis of epigenetic linkages to the DNA Damage Response are challenging owing to the random nature of exogenous DSB induction. Here, we directly measure stochastic DNA damage induced by ionizing radiation (IR) and infer relationships between basal epigenetic states and cellular ability to detect DSBs. Contrary to the expected uniform localization of DSBs and γH2AX, we show that DSB recognition is separate from DSB induction and that both processes are dependent on the local chromatin milieu. In general, actively transcribed regions contain more γH2AX than heterochromatic regions suggesting a link between transcription and the DDR. In contrast to previous studies, we suggest that transcription proximal to DNA damage is necessary for early DSB detection and suggest a requirement for transcription mediated repair in genome maintenance. Finally, we reveal a dual effect of the repressive mark H3K27me3 on the DNA damage response. While basal H3K27me3 attenuates γH2AX deposition, transcribed regions recruit H3K27me3 following DSB induction possibly as an obligate step in DSB recognition. We uncover epigenetic determinants of DSB recognition and suggest new mechanisms by which the epigenome direct DNA repair. Our findings suggest new targets for radio-adjuvant therapy and reframe the current stochastic model of radiotherapy induced damage.

2021-12-31 | GSE181934 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data