Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA87685 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:p38-MK2 regulate RNA metabolism after UV light-induced DNA damage
| PRJNA355010 | ENA
Project description:p38-MK2 regulate RNA metabolism after UV light-induced DNA damage
| PRJNA355009 | ENA
Project description:While it is well-established that UV radiation threatens genomic integrity, the precise mechanisms by which cells orchestrate DNA damage response and repair within the context of 3D genome architecture remain unclear. Here, we address this gap by investigating the UV-induced reorganization of the 3D genome and its critical role in mediating damage response. Employing temporal maps of contact matrices and transcriptional profiles, we illustrate the immediate and holistic changes in genome architecture post-irradiation, emphasizing the significance of this reconfiguration for effective DNA repair processes. We demonstrate that UV radiation triggers a comprehensive restructuring of the 3D genome structure at all levels, including loops, topologically associating domains and compartments. Through the analysis of DNA damage and excision repair maps, we uncover a correlation between genome folding, gene regulation, damage formation probability, and repair efficacy. We show that adaptive reorganization of the 3D genome is a key mediator of the damage response, providing new insights into the complex interplay of genomic structure and cellular defense mechanisms against UV-induced damage, thereby advancing our understanding of cellular resilience.
2024-05-27 | GSE268350 | GEO
Project description:While it is well-established that UV radiation threatens genomic integrity, the precise mechanisms by which cells orchestrate DNA damage response and repair within the context of 3D genome architecture remain unclear. Here, we address this gap by investigating the UV-induced reorganization of the 3D genome and its critical role in mediating damage response. Employing temporal maps of contact matrices and transcriptional profiles, we illustrate the immediate and holistic changes in genome architecture post-irradiation, emphasizing the significance of this reconfiguration for effective DNA repair processes. We demonstrate that UV radiation triggers a comprehensive restructuring of the 3D genome structure at all levels, including loops, topologically associating domains and compartments. Through the analysis of DNA damage and excision repair maps, we uncover a correlation between genome folding, gene regulation, damage formation probability, and repair efficacy. We show that adaptive reorganization of the 3D genome is a key mediator of the damage response, providing new insights into the complex interplay of genomic structure and cellular defense mechanisms against UV-induced damage, thereby advancing our understanding of cellular resilience.
2024-05-27 | GSE268349 | GEO
Project description:p38-MK2 signaling axis regulates RNA metabolism after UV light-induced DNA damage
| PRJNA392173 | ENA
Project description:Solar radiation is the major source of human exposure to UV radiation, the major carcinogen in skin cancers, by triggering a number of cellular responses that can indirectly or directly induce DNA damage. Skin cells attempt to repair these damages by activating cascades of DNA Damage Response mechanisms to safeguard genome integrity, thereby preventing skin cancers. The role of PPARb - a druggable transcription factor, in the development of UV-dependent skin cancers is not mechanistically elucidated. We have shown previously that PPARb knockout mice are less prone to UV-induced skin cancers. Here, we report on our global transcriptomic analysis revealing that PPARb directly regulates gene expression programs associated with cell cycle and DNA repair pathways in normal human epidermal keratinocytes. We show that in these cells, as well as in malignant human keratinocytes and in human melanoma cells, PPARb controls cellular proliferation and cell cycle progression and its depletion leads to cell cycle arrest. We also show that PPARb controls the response of normal human epidermal keratinocytes to UV-induced DNA damage. PPARb depletion decreases the expression and/or activation of multiple effectors of DNA Damage Response (DDR) pathway and favours the apoptotic response of human keratinocytes to UV irradiation. Our preclinical data of a PDX melanoma model demonstrated that the depletion or inhibition of PPARb delays of blocks tumor formation. Our data suggest that PPARb inhibition can be considered as a therapeutic target for the prevention of UV-induced skin cancers in vulnerable population, by attenuating the DDR and eliminating skin cells with high UV-induced mutational burden.
2024-12-18 | GSE263846 | GEO
Project description:Ultraviolet (UV) light radiation induces the formation of bulky photoproducts in the DNA that globally affect transcription and splicing. However, the signaling pathways and mechanisms that link UV light-induced DNA damage to changes in RNA metabolism remain poorly understood. Here, we employ quantitative phosphoproteomics and protein kinase inhibition to provide a systems view on protein phosphorylation patterns induced by UV light, and uncover the dependencies of phosphorylation events on the canonical DNA damage signaling by ATM/ATR and the p38 MAP kinase pathway. We identify RNA binding proteins as primary substrates and 14-3-3 as direct readers of p38-MK2-dependent phosphorylation induced by UV light. Mechanistically, we show that MK2 phosphorylates the RNA binding subunit of the NELF complex NELFE on Serine 115. NELFE phosphorylation promotes the recruitment of 14-3-3 and rapid dissociation of the NELF complex from chromatin, which is accompanied by RNA polymerase II elongation.
2018-02-08 | GSE100580 | GEO
Project description:Ultraviolet (UV) light radiation induces the formation of bulky photoproducts in the DNA that interfere with replication and transcription. Recent studies showed that exposure of human cells to UV light globally affects transcription and alternative splicing, however, the signaling pathways and mechanisms that link UV light-induced DNA damage to RNA metabolism regulation remain poorly understood. Here, we provide a systems view on protein phosphorylation patterns induced by UV light, and uncover the dependencies of phosphorylation events on the canonical DNA damage signaling mediated by ATM/ATR or p38 MAP kinase pathway. We identify RNA binding proteins as primary targets and 14-3-3 family as direct readers of p38-MK2-dependent phosphorylation induced by UV light. Moreover, we show that MK2 phosphorylates the RNA binding subunit of the NELF complex NELFE on S115. NELFE phosphorylation promotes the recruitment of 14-3-3 and rapid dissociation of the NELF complex from chromatin that is accompanied with an increase in transcriptional elongation.
2018-02-09 | PXD004255 | Pride
Project description:Genome-wide DNA damage response following ionizing radiation
| PRJNA258468 | ENA
Project description:Mechanistic model of the Post-Replication Repair (PRR), the pathway involved in the bypass
of DNA lesions induced by sunlight exposure and UV radiation. PRR acts through two different mechanisms,
activated by mono- and poly-ubiquitylation of the DNA sliding clamp, called Proliferating Cell Nuclear Antigen (PCNA).
This model has been defined according to the stochastic formulation of chemical kinetics [Gillespie DT, J Phys Chem 1977, 81(25):2340-2361],
which requires to specify the set of molecular species occurring in the pathway and their respective interactions,
formally described as a set of biochemical reactions.
The volume considered for this system is 1.666667e-17L; this value can be used to convert the model into the deterministic formulation.
2024-09-02 | BIOMD0000000475 | BioModels