Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA98485 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The changes in global gene expression in response to DNA damage may derive from either direct induction or repression by transcriptional regulation or indirectly by synchronization of cells to specific cell cycle phases, such as G1 or G2. We developed a model that successfully estimated the expression levels of >400 cell-cycle-regulated genes in normal human fibroblasts based on the proportions of cells in each phase of the cell cycle. By isolating effects on the gene expression associated with the cell cycle phase redistribution after genotoxin treatment, the direct transcriptional target genes were distinguished from genes for which expression changed secondary to cell synchronization. Application of this model to ionizing radiation (IR)-treated normal human fibroblasts identified 150 of 406 cycle-regulated genes as putative direct transcriptional targets of IR-induced DNA damage. Changes in expression of these genes after IR treatment derived from both direct transcriptional regulation and cell cycle synchronization. Keywords: Microarray, Cell cycle, Ionizing radiation, Human fibroblasts, EPIG
2007-08-01 | GSE7075 | GEO
Project description:The hereditary information encoded in DNA sequence is intrinsically susceptible to alterations, being continually threatened by a variety of genotoxic perturbations. To safeguard the stability of the genome, eukaryotic cells have evolved a set of sophisticated surveillance system that controls several aspects of the cellular response, including the detection of DNA lesions, a temporary cell cycle arrest, regulation of transcription, and the repair of the damaged DNA. However, it is still poorly understood how the DNA damage checkpoints and stalled RNAPII molecules convert a very limited amount of molecular-level information (even a single DNA lesion) in the context of an otherwise genome into regulation that halts and resumes the cell-cycle engine in a coordinated way. In this study, we reveal a map of extensive lncRNA transcription during DDR by using synchronized cells, leading to the unexpected identification of a poorly characterized mammalian lncRNA-ZFAS1. We describe that ZFAS1 functions as a key player of cellular response to DNA damage in both human and rodent cells by fine tuning RNAPII kinetics, suggesting a lncRNA-dependent transcriptional regulatory axis that maintains genomic stability upon DNA damage in mammalian cells.
2023-08-03 | GSE239616 | GEO
Project description:The hereditary information encoded in DNA sequence is intrinsically susceptible to alterations, being continually threatened by a variety of genotoxic perturbations. To safeguard the stability of the genome, eukaryotic cells have evolved a set of sophisticated surveillance system that controls several aspects of the cellular response, including the detection of DNA lesions, a temporary cell cycle arrest, regulation of transcription, and the repair of the damaged DNA. However, it is still poorly understood how the DNA damage checkpoints and stalled RNAPII molecules convert a very limited amount of molecular-level information (even a single DNA lesion) in the context of an otherwise genome into regulation that halts and resumes the cell-cycle engine in a coordinated way. In this study, we reveal a map of extensive lncRNA transcription during DDR by using synchronized cells, leading to the unexpected identification of a poorly characterized mammalian lncRNA-ZFAS1. We describe that ZFAS1 functions as a key player of cellular response to DNA damage in both human and rodent cells by fine tuning RNAPII kinetics, suggesting a lncRNA-dependent transcriptional regulatory axis that maintains genomic stability upon DNA damage in mammalian cells.
2023-08-03 | GSE239615 | GEO
Project description:The hereditary information encoded in DNA sequence is intrinsically susceptible to alterations, being continually threatened by a variety of genotoxic perturbations. To safeguard the stability of the genome, eukaryotic cells have evolved a set of sophisticated surveillance system that controls several aspects of the cellular response, including the detection of DNA lesions, a temporary cell cycle arrest, regulation of transcription, and the repair of the damaged DNA. However, it is still poorly understood how the DNA damage checkpoints and stalled RNAPII molecules convert a very limited amount of molecular-level information (even a single DNA lesion) in the context of an otherwise genome into regulation that halts and resumes the cell-cycle engine in a coordinated way. In this study, we reveal a map of extensive lncRNA transcription during DDR by using synchronized cells, leading to the unexpected identification of a poorly characterized mammalian lncRNA-ZFAS1. We describe that ZFAS1 functions as a key player of cellular response to DNA damage in both human and rodent cells by fine tuning RNAPII kinetics, suggesting a lncRNA-dependent transcriptional regulatory axis that maintains genomic stability upon DNA damage in mammalian cells.
2023-08-03 | GSE239614 | GEO
Project description:The hereditary information encoded in DNA sequence is intrinsically susceptible to alterations, being continually threatened by a variety of genotoxic perturbations. To safeguard the stability of the genome, eukaryotic cells have evolved a set of sophisticated surveillance system that controls several aspects of the cellular response, including the detection of DNA lesions, a temporary cell cycle arrest, regulation of transcription, and the repair of the damaged DNA. However, it is still poorly understood how the DNA damage checkpoints and stalled RNAPII molecules convert a very limited amount of molecular-level information (even a single DNA lesion) in the context of an otherwise genome into regulation that halts and resumes the cell-cycle engine in a coordinated way. In this study, we reveal a map of extensive lncRNA transcription during DDR by using synchronized cells, leading to the unexpected identification of a poorly characterized mammalian lncRNA-ZFAS1. We describe that ZFAS1 functions as a key player of cellular response to DNA damage in both human and rodent cells by fine tuning RNAPII kinetics, suggesting a lncRNA-dependent transcriptional regulatory axis that maintains genomic stability upon DNA damage in mammalian cells.
2023-08-03 | GSE239613 | GEO
Project description:The TEA domain family members 1-4 (TEADs) are major transcription factors for YAP/TAZ transcription activators in the Hippo pathway, regulating many biological processes, including development, tissue homeostasis, and tumorigenesis through target genes. Their amplification/upregulation correlates with poor prognosis in cancer patients. Although the Hippo pathway continues to be elucidated, it is clear that TEAD largely exerts its actions via transcriptional regulation. Here, we uncover an unexpected role for TEADs in the DNA damage response. Using comparative mass spectrometry, we demonstrate that TEADs interact with several DNA repair proteins. We further show that TEADs form DNA damage-induced nuclear foci that co-localize with DNA damage markers. We also found that TEADs are required for resistance to DNA damage, maintaining genome stability, and resolution of double strand break repair that is independent from the Hippo pathway and its transcriptional role. Our results establish a new role for TEADs in DNA repair and therefore, highlight a critical consideration in therapeutically targeting the Hippo pathway.
2022-11-21 | MSV000090760 | MassIVE
Project description:After DNA damage, cells activate p53, a tumor suppressor gene, and select a cell fate (e.g., DNA repair, cell cycle arrest, or apoptosis). Recently, a p53 oscillatory behavior was observed following DNA damage. However, the relationship between this p53 oscillation and cell-fate selection is unclear. Here, we present a novel model of the DNA damage signaling pathway that includes p53 and whole cell cycle regulation and explore the relationship between p53 oscillation and cell fate selection. The simulation run without DNA damage qualitatively realized experimentally observed data from several cell cycle regulators, indicating that our model was biologically appropriate. Moreover, the comprehensive sensitivity analysis for the proposed model was implemented by changing the values of all kinetic parameters, which revealed that the cell cycle regulation system based on the proposed model has robustness on a fluctuation of reaction rate in each process. Simulations run with four different intensities of DNA damage, i.e. Low-damage, Medium-damage, High-damage, and Excess-damage, realized cell cycle arrest in all cases. Low-damage, Medium-damage, High-damage, and Excess-damage corresponded to the DNA damage caused by 100, 200, 400, and 800 J/m(2) doses of UV-irradiation, respectively, based on expression of p21, which plays a crucial role in cell cycle arrest. In simulations run with High-damage and Excess-damage, the length of the cell cycle arrest was shortened despite the severe DNA damage, and p53 began to oscillate. Cells initiated apoptosis and were killed at 400 and 800 J/m(2) doses of UV-irradiation, corresponding to High-damage and Excess-damage, respectively. Therefore, our model indicated that the oscillatory mode of p53 profoundly affects cell fate selection.
2024-09-02 | BIOMD0000000939 | BioModels
Project description:Kollarovic2016 - Cell fate decision at G1-S
transition
This model is described in the article:
To senesce or not to
senesce: how primary human fibroblasts decide their cell fate
after DNA damage.
Kollarovic G, Studencka M, Ivanova
L, Lauenstein C, Heinze K, Lapytsko A, Talemi SR, Figueiredo AS,
Schaber J.
Aging (Albany NY) 2016 Jan;
Abstract:
Excessive DNA damage can induce an irreversible cell cycle
arrest, called senescence, which is generally perceived as an
important tumour-suppressor mechanism. However, it is unclear
how cells decide whether to senesce or not after DNA damage. By
combining experimental data with a parameterized mathematical
model we elucidate this cell fate decision at the G1-S
transition. Our model provides a quantitative and conceptually
new understanding of how human fibroblasts decide whether DNA
damage is beyond repair and senesce. Model and data imply that
the G1-S transition is regulated by a bistable hysteresis
switch with respect to Cdk2 activity, which in turn is
controlled by the Cdk2/p21 ratio rather than cyclin abundance.
We experimentally confirm the resulting predictions that to
induce senescence i) in healthy cells both high initial and
elevated background DNA damage are necessary and sufficient,
and ii) in already damaged cells much lower additional DNA
damage is sufficient. Our study provides a mechanistic
explanation of a) how noise in protein abundances allows cells
to overcome the G1-S arrest even with substantial DNA damage,
potentially leading to neoplasia, and b) how accumulating DNA
damage with age increasingly sensitizes cells for
senescence.
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2024-09-02 | BIOMD0000000632 | BioModels
Project description:p53 is a critical tumor suppressor and works as a stress-induced transcription factor to induce target genes mediating apoptosis, cell cycle arrest and senescence or other responses. To gain new insights into p53 biology, we used high-throughput sequencing to analyze global p53 transcriptional networks in primary mouse embryo fibroblasts in response to DNA damage. ChIP-sequencing reveals 4785 p53-bound sites in the genome located near 3193 genes involved in diverse biological processes. RNA-sequencing analysis shows that only a subset of p53-bound genes is transcriptionally regulated, yielding a list of 432 p53-bound and regulated genes. Furthermore, we define a list of 1269 basal-p53 regulated genes, of which 253 are p53-bound and basal-p53 regulated. ChIP-seq was performed to determine the genome-wide p53 binding sites in doxorubicin-treated primary MEFs. RNA-seq was used to define differentially expressed genes in response to DNA damage in wild-type and p53-/- MEFs, and basal p53 regulated genes by deriving differentially expressed genes between untreated wild-type and p53-/- MEFs.
2013-04-21 | E-GEOD-46240 | biostudies-arrayexpress
Project description:To identify potential regulators involved in virus-triggered innate immune response, we used tandem mass tagging (TMT)-based shotgun proteomic analysis of murine bone marrow-derived macrophages (BMDMs) following sendai virus (SeV) infection. This approach facilitated the identification and relative quantification of up- or down-regulated proteins, as evaluated by replicates. Kyoto encyclopedia of genes and genomes (KEGG) analysis indicated that proteins involved in innate immune and inflammatory responses significantly increased following SeV infection. Surprisingly, we also observed a series of proteins involved in the regulation of cell cycle and DNA damage repair process were greatly impaired after SeV infection.
2025-04-03 | PXD051098 | Pride