Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA135585 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Maintenance of genomic stability depends on the DNA damage response (DDR), a biological barrier in early stages of cancer development. Failure of this response results in genomic instability and high predisposition toward lymphoma, as seen in patients with ataxia-telangiectasia mutated (ATM) dysfunction. ATM activates multiple cell cycle checkpoints and DNA repair following DNA damage, but its influence on posttranscriptional gene expression has not been examined on a global level. We show that ionizing radiation (IR) modulates the dynamic association of the RNA-binding protein HuR with target mRNAs in an ATM-dependent manner, potentially coordinating the genotoxic response as an RNA operon. Pharmacologic ATM inhibition and use of ATM-null cells revealed a critical role for ATM in this process. Numerous mRNAs encoding cancer-related proteins were differentially associated with HuR depending on the functional state of ATM, in turn affecting expression of encoded proteins. The findings presented here reveal a previously unidentified role of ATM in controlling gene expression post-transcriptionally. Dysregulation of this DDR RNA operon is likely relevant to lymphoma development in ataxia-telangiectasia individuals. These novel RNA regulatory modules and genetic networks provide critical insight into the function of ATM in oncogenesis.
2011-01-05 | GSE25848 | GEO
Project description:DNA damage response kinase ATM regulates the genetic program of lymphocytes with phsiologically induced DNA DSBs. In bone marrow-derived macrophages, related kinase DNAPKcs is also responsible for activating DNA damage responses after infection with Listeria monocytogenes. Here we show that both ATM and DNA-PKcs regulate the genetic program of Listeria monocytogenes-infected macrophages.
2015-07-03 | GSE70467 | GEO
Project description:DNA damage response kinase ATM regulates the genetic program of lymphocytes with phsiologically induced DNA DSBs. In bone marrow-derived macrophages, related kinase DNAPKcs is also responsible for activating DNA damage responses after infection with Listeria monocytogenes. Here we show that both ATM and DNA-PKcs regulate the genetic program of Listeria monocytogenes-infected macrophages. Two independent bone marrow-derived macrophage cultures for each genotype (LysMcre/+ and Scid: Atmc/c: LysMcre/+) were infected with Listeria monocytogenes for 24 hrs at an MOI of 5. RNA was isolated using RNeasy (Qiagen). Gene expression profiling was performed using Illumina MouseRef-8 expression microarrays.
2015-07-03 | E-GEOD-70467 | biostudies-arrayexpress
Project description:Maintenance of genomic stability depends on the DNA damage response (DDR), a biological barrier in early stages of cancer development. Failure of this response results in genomic instability and high predisposition toward lymphoma, as seen in patients with ataxia-telangiectasia mutated (ATM) dysfunction. ATM activates multiple cell cycle checkpoints and DNA repair following DNA damage, but its influence on posttranscriptional gene expression has not been examined on a global level. We show that ionizing radiation (IR) modulates the dynamic association of the RNA-binding protein HuR with target mRNAs in an ATM-dependent manner, potentially coordinating the genotoxic response as an RNA operon. Pharmacologic ATM inhibition and use of ATM-null cells revealed a critical role for ATM in this process. Numerous mRNAs encoding cancer-related proteins were differentially associated with HuR depending on the functional state of ATM, in turn affecting expression of encoded proteins. The findings presented here reveal a previously unidentified role of ATM in controlling gene expression post-transcriptionally. Dysregulation of this DDR RNA operon is likely relevant to lymphoma development in ataxia-telangiectasia individuals. These novel RNA regulatory modules and genetic networks provide critical insight into the function of ATM in oncogenesis. B-lymphocyte cell lines GM02184 (wild type, ATM +/+) and GM03332 (AT, ATM -/-) were either untreated or exposed to 1 Gy of IR. 6 h later cells were harvested and used for immunoprecipitation (IP) in the presence of HuR antibody (Santa Cruz Biotech.). RNA from IP material was extracted and used for microarray analysis.
2011-01-05 | E-GEOD-25848 | biostudies-arrayexpress
Project description:Ataxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response and is associated with cancer suppression. Here, we used microarray to study global transcriptomic expression to identify tumor-promoting functions of ATM. Human breast cancer MDA-MB-231 cells were transfected with siATM, sip53 or control siRNA followed by RNA extraction and hybridization on Affymetrix GeneChip Human Gene 2.0 ST array.
2014-08-18 | E-GEOD-60479 | biostudies-arrayexpress
Project description:Ataxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response and is associated with cancer suppression. Here, we used microarray to study global transcriptomic expression to identify tumor-promoting functions of ATM.
2014-08-18 | GSE60479 | GEO
Project description:Ribosomal DNA (rDNA) arrays are highly repetitive regions of the genome which encode essential genes required to produce ribosomes. DNA double-stranded breaks (DSBs) generated within rDNA genes elicit a unique cellular response involving robust transcriptional silencing and nucleolar reorganization into ‘cap’ structures at the nucleolar periphery. This process is coordinated by the nucleolar scaffolding protein TCOF1, which functions to recruit the DNA repair proteins NBS1 and TOPBP1 that activate the ATM and ATR kinases, resulting in ribosomal RNA (rRNA) transcriptional silencing and nucleolar segregation. However, the DNA damage and repair response at rDNA arrays remains incompletely understood. Here, we investigate the cellular response to rDNA DSBs using proteomics and genetic CRISPR-Cas9 screening. We show that the protein UFMylation pathway and the HUSH complex are important for cell viability and survival in response to rDNA DSBs, and that the E3 UFM1-ligase UFL1 and its heterodimer DDRGK1 are associated with TCOF1 at nucleolar caps. Loss of UFL1 leads to impaired ATM activation, reduced rRNA transcriptional silencing, and an overall reduction in nucleolar segregation. We identified ATM, UNC45A and SMC6 as UFMylated proteins, in which UFMylation may facilitate ATM activation and segregation of damaged rDNA to the nucleolar periphery. Altogether, our findings provide the first evidence for a role for UFMylation in rDNA DSB repair.
2024-09-16 | PXD048568 | Pride
Project description:Emerging and neglected pathogens pose challenges as their biology is frequently poorly understood, and genetic tools often do not exist to manipulate them. Organism agnostic sequencing technologies offer a promising approach to understand the molecular processes underlying these diseases. Here we apply dual RNA-seq to Orientia tsutsugamushi (Ot), the obligate intracellular causative agent of the vector-borne human disease scrub typhus. Half the Ot genome is composed of repetitive DNA, and there is minimal collinearity in gene order between strains. Integrating RNA-seq, comparative genomics, proteomics, and machine learning, we investigated the transcriptional architecture of Ot, including operon structure and non-coding RNAs, and found evidence for wide-spread post-transcriptional antisense regulation. We compared the host response to two clinical isolates and identified distinct immune response networks that are up-regulated in response to each strain, leading to predictions of relative virulence which were confirmed in a mouse infection model. Thus, dual RNA-seq can reveal the biology and host-pathogen interactions of a poorly characterized and genetically intractable organism such as Ot.
2020-06-05 | PXD017956 | JPOST Repository
Project description:Atm+/+ and Atm-/- mouse embryonic fibroblasts were treated with or without DNA damaging agent neocarzinostatin (NCS), and cells were harvested after 4 hours and 8 hours for the microarray analyses of whole-genome long noncoding RNAs. To examine how long noncoding RNAs are regulated in the DNA damage response, we assessed the genome-wide long noncoding RNA expression in Atm+/+ and Atm-/- littermate mouse embryonic fibroblasts (MEFs) treated with or without DNA damage
2013-01-17 | E-GEOD-43425 | biostudies-arrayexpress
Project description:Post-transcriptional regulation of cellular mRNA is essential for protein synthesis. Here we describe the importance of mRNA translational repression and mRNA subcellular location for protein expression during B lymphocyte activation and the DNA damage response. Cytoplasmic RNA granules are formed upon cell activation with mitogens, including stress granules that contain the RNA binding protein Tia1. Tia1 binds to a subset of transcripts involved in cell stress, including p53 mRNA, and controls translational silencing and RNA granule localization. DNA damage promotes mRNA relocation and translation in part due to dissociation of Tia1 from its mRNA targets. Upon DNA damage, p53 mRNA is released from stress granules and associates with polyribosomes to increase protein synthesis. Global analysis of cellular mRNA abundance and translation indicates that this is an extended ATM-dependent mechanism to increase protein expression of key modulators of the DNA damage response.
2017-09-13 | GSE93575 | GEO