Identification of novel gene targets and functions of p21-activated kinase 1 during DNA damage by gene expression profiling
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE47503 | GEO | 2016/01/01
SECONDARY ACCESSION(S): PRJNA205899
REPOSITORIES: GEO
Similar Datasets
Project description:The purpose of the study was to identify new PAK1 targets in response to ionizing radiation with putative role in the DNA damage response. We examined the effect of IR on the gene expression patterns in the murine embryonic fibroblasts with or without Pak1 using microarray. Differentially expressed transcripts were identified using Gene Spring GX 10.0.2. The samples used were Wild type, Pak1 knock out, Wild type treated with ionizing radiation and Pak1 knock out treated with ionizing radiation. Triplicates of each sample type were used for analysis.
2016-07-03 | E-GEOD-47503 | biostudies-arrayexpress
Project description:Genotoxic damage is known to disrupt cellular functions and is lethal if not repaired properly. We compare the transcriptional programs activated in response to genotoxic DNA damage induced by ionizing radiation (IR) in pre-B cells from mice deficient in various DNA damage response (DDR) genes. We used microarrays to detail the global gene expression of mutated cells compared to WT cells, with and without exposure to the DNA damaging agent ionizing radiation (IR), and identified differentially-regulated genes and associated pathways responding to the damage.
2019-11-15 | GSE116388 | GEO
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
Project description:Growing interest in the cellular origins of different breast cancer subtypes has prompted investigations into the subpopulations of the normal breast epithelia and their differentiation hierarchy. Several groups have demonstrated a likely luminal-progenitor cell origin for basal-like breast cancer. However, the molecular and cellular mechanisms underlying why one breast cell type might be more susceptible to transformation are yet to be elucidated. To observe the molecular differences in the different cell subpopulation response to ionizing radiation (IR), we performed gene expression profiling of MUC1+-sorted and CD10+-sorted primary human mammary epithelial cell cultures. Transcriptional response was measured at 2 and 24 hr after treatment with 2 and 5 Gy IR using Illumina HumanHT-12 v4 Expression Beadchips. The complete sample cohort included time-point matched untreated (0 Gy) controls in a total of 5 individual patients. Our analyses indicated several cell-type specific differences in response to IR. RNA was extracted from MUC1+-sorted and CD10+-sorted primary human mammary epithelial cell cultures at 2 and 24 hr after treatment with 0, 2, and 5 Gy ionizing radiation (12 samples per patient), in a total of 5 individual patients.
2016-02-07 | E-GEOD-67595 | biostudies-arrayexpress
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:Ionizing radiation (IR) – induced salivary gland damage is a common adverse effect in radiotherapy for patients with head and neck cancers. Currently, there is no effective treatment for the resulting salivary gland hypofunction and xerostomia (dry mouth). Here we profiled the acute gene expression change in the mouse submandibular salivary gland, and defined its damage response patterns at the transcriptome level.
2021-09-23 | GSE184673 | GEO
Project description:The relationships between profiles of global gene expression and DNA damage checkpoint functions were studied in cells from patients with ataxia telangiectasia (AT). Three telomerase-expressing AT fibroblast lines displayed the expected hypersensitivity to ionizing radiation (IR) and defects in DNA damage checkpoints. Profiles of global gene expression in AT cells were determined at 2, 6 and 24 h after treatment with 1.5 Gy IR or sham-treatment, and were compared to those previously recognized in normal human fibroblasts. Under basal conditions 160 genes or ESTs were differentially expressed in AT and normal fibroblasts, and these were associated by gene ontology with insulin-like growth factor binding and regulation of cell growth. Upon DNA damage, 1091 gene mRNAs were changed in at least two of the three AT cell lines. When compared with the 1811 genes changed in normal human fibroblasts after the same treatment, 715 were found in both AT and normal fibroblasts, including most genes categorized by gene ontology into cell cycle, cell growth and DNA damage response pathways. However, the IR-induced changes in these 715 genes in AT cells usually were delayed or attenuated in comparison to normal cells. The reduced change in DNA-damage-response genes and the attenuated repression of cell-cycle-regulated genes may account for the defects in cell cycle checkpoint function in AT cells. The observation of attenuated and not ablated checkpoint responses in AT cells supports a hypothesis that the ATM- and rad3-related checkpoint kinase ATR also responds to IR-induced DNA damage and complements ATM signaling. Keywords: ATM, cell cycle checkpoint, ionizing radiation, microarray
2007-07-01 | GSE6971 | GEO
Project description:Treatment with ionizing irradiation (IR) may lead to accumulation of tumor-infiltrating T regulatory (Treg) cells and subsequent tumor resistance to radiotherapy. Here we focused on the contribution of Langerhans cells (LCs) to this phenomenon because of their unique ability to resist depletion by high-dose IR. We found that LCs resisted apoptosis and rapidly repaired DNA damage post-IR. Particularly, we found that p21 was overexpressed in LCs, and that p21-deficient LCs underwent apoptosis and accumulated DNA damage following IR treatment. Wild-type, but not p21-deficient, LCs upregulated major histocompatibility complex class II molecules, migrated to the draining lymph nodes and increased Treg cell numbers upon exposure to IR. These findings suggest a means for manipulating LC IR-resistance to increase cutaneous tumor response to radiotherapy. See above Cells were purified by flow cytometry and pooled until >10,000 cells/sample. At least 2 replicates of each sample were submitted.
2015-07-25 | E-GEOD-71330 | biostudies-arrayexpress
Project description:Control and RBM6-KO MCF10A-Hras cells were subjected to RNA-sequencing before and after 12hrs exposure to 5Gy ionizing radiation (IR). Transcriptome analysis revealed a subset of genes that are differentially regulated in RBM6-KO cells compared to control cells. In addition, transcriptome of RBM6-KO cells after IR showed upregulation of DNA damage genes, suggesting impaired DNA repair compared to control cells.
2021-03-23 | GSE167265 | GEO
Project description:Treatment with ionizing irradiation (IR) may lead to accumulation of tumor-infiltrating T regulatory (Treg) cells and subsequent tumor resistance to radiotherapy. Here we focused on the contribution of Langerhans cells (LCs) to this phenomenon because of their unique ability to resist depletion by high-dose IR. We found that LCs resisted apoptosis and rapidly repaired DNA damage post-IR. Particularly, we found that p21 was overexpressed in LCs, and that p21-deficient LCs underwent apoptosis and accumulated DNA damage following IR treatment. Wild-type, but not p21-deficient, LCs upregulated major histocompatibility complex class II molecules, migrated to the draining lymph nodes and increased Treg cell numbers upon exposure to IR. These findings suggest a means for manipulating LC IR-resistance to increase cutaneous tumor response to radiotherapy. See above
2015-07-25 | GSE71330 | GEO