Unknown,Transcriptomics,Genomics,Proteomics

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Human Fibroblast cells immortalised cells: Control vs DNA damage

ABSTRACT: Transcriptional profiling of human fibroblast cells after DNA damage with Camptothecin or Etoposide or Neocarzinostatin Upon DNA damage, the DNA damage response (DDR) elicits a complex signaling cascade, which includes the induction of multiple non-coding RNA species. Recently long non-coding RNAs (lncRNAs) have been shown to contribute to DDR by regulating gene expression. However, very little is known about the role that lncRNAs play in regulating DNA Repair. Using a genome-wide microarray screen we identified a novel ubiquitously expressed lncRNA, DDSR1 (DNA damage-sensitive RNA 1), which is induced upon DNA damage by several DNA double-strand break (DSB) agents. Two-condition experiment, Control vs. DNA damage human fibroblast cells. No Replicates, DNA damage was induced with either Camptothecin or Etoposide or Neocarzinostatin, Total RNA or Nuclear RNA was profiled.

ORGANISM(S): Homo sapiens

SUBMITTER: Vivek Sharma

PROVIDER: E-GEOD-67062 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:DNA damage response (DDR) is a complex process, essential for cell survival. Especially deleterious type of DNA damage are DNA double-strand breaks (DSB), which can lead to genomic instability and malignant transformation if not repaired correctly. The central player in DSB detection and repair is the ATM kinase which orchestrates the action of several downstream factors. Despite substantial knowledge of DNA repair processes, still several aspects of DNA damage detection and signaling are not fully understood. Recent studies have suggested that long non-coding RNAs (lncRNAs) are involved in DDR. Here, we aimed to identify lncRNAs induced upon DNA damage in an ATM-dependent manner. 7 mRNAs and 10 lncRNAs were significantly induced 1h after ionizing radiation (IR) in healthy donors, whereas none in AT patients. 447 mRNAs and 149 lncRNAs were induced 8h after IR in the control group, while only 100 mRNAs and 3 lncRNAs in AT patients. Among IR-induced mRNAs, we found several genes with well-known functions in DDR. Gene Set Enrichment Analysis and Gene Ontology revealed delayed induction of key DDR pathways in AT patients compared to controls. The induction and dynamics of selected 9 lncRNAs were confirmed by RT-qPCR at several time-points after IR on a larger cohort. Moreover, inhibition of ATM with a specific inhibitor (KU-60019) proved that those lncRNAs are dependent on ATM. Some of the detected lncRNAs are localized next to protein-coding genes involved in DDR. We observed that induction of lncRNAs after IR preceded changes in expression of adjacent genes. This indicates that IR-induced lncRNAs may regulate the transcription of nearby genes. Subcellular fractionation into chromatin, nuclear, and cytoplasmic fractions revealed that the majority of studied lncRNAs are localized in chromatin, which further suggests their role in regulation of gene expression. In summary, our study revealed several lncRNAs induced by IR in an ATM-dependent manner. Their co-localization and co-expression with genes involved in DDR suggest that those lncRNAs may be important players in cellular response to DNA damage.

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Human Fibroblast cells immortalised cells: Control vs DNA damage

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