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Status |
Public on Sep 01, 2015 |
Title |
Identification of diffrentially expressed genes upon DDSR1 knockdown |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
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. DDSR1 induction upon DNA damage is dependent on the ATM-NF-kB pathway but p53 independent. However, DDSR1 acts in the p53 network by negatively regulating p53 mediated gene expression. Loss of DDSR1 impairs cell proliferation, DDR signaling and reduces DNA repair capacity by homologous recombination (HR). The HR defect upon DDSR1 knockdown is due to reduced end resection caused by aberrant BRCA1 and RAP80 accumulation at DSB sites. In line with dual role of DDSR1 in gene regulation and HR, DDSR1 interacts with hnRNPUL1, an RNA-binding protein involved in transcription and HR. Our results reveal a previously unknown lncRNA involved in regulation of DDR by contributing to gene regulation and DNA repair by HR. Our findings highlight the importance of DDSR1 in maintaining genome stability and suggest that the DDR is even more complex than currently assumed. We used microarrays to identify gene expression changes upon DDSR1 knockdown
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Overall design |
hTERT immortalised Human Fibroblast cells were transfected a non specific siRNA or siRNA against DDSR1,72 hours post transfection RNA was isolated and process for Microarray. 3 Biological Replicates
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Contributor(s) |
Sharma V, Misteli T |
Citation(s) |
26412854, 26697398 |
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Submission date |
Mar 18, 2015 |
Last update date |
Dec 24, 2015 |
Contact name |
Vivek Sharma |
E-mail(s) |
vivek.sharma@nih.gov
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Phone |
3014352672
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Organization name |
NCI
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Department |
CCR
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Lab |
LRBGE
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Street address |
41 Library Drive
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City |
Bethesda |
State/province |
MD |
ZIP/Postal code |
20892 |
Country |
USA |
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Platforms (1) |
GPL19251 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [probe set (exon) version] |
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Samples (6)
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This SubSeries is part of SuperSeries: |
GSE72358 |
A BRCA1 interacting lncRNA regulates homologous recombination |
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Relations |
BioProject |
PRJNA278848 |
Supplementary file |
Size |
Download |
File type/resource |
GSE67048_RAW.tar |
71.9 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
Processed data included within Sample table |
Processed data provided as supplementary file |
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