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Status |
Public on Dec 08, 2018 |
Title |
Nuclear phosphorylated Dicer processes double-stranded RNA in response to DNA damage |
Organism |
Homo sapiens |
Experiment type |
Other Genome binding/occupancy profiling by high throughput sequencing
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Summary |
The endonuclease Dicer is a key component of the human RNA interference (RNAi) pathway and known for its role in cytoplasmic micro RNA (miRNA) production. Recent findings suggest that non-canonical Dicer generates small non-coding RNA (ncRNA) to mediate the DNA damage response (DDR). Here we show that human Dicer is phosphorylated in the platform-PAZ-connector helix cassette (S1016) upon induction of DNA damage. Phosphorylated Dicer (p-Dicer) accumulates in the nucleus and is recruited to DNA double-strand breaks (DSBs). We further demonstrate that turnover of damage-induced nuclear dsRNA requires additional phosphorylation of carboxy-terminal Dicer residues (S1728 and S1852). DNA damage-induced nuclear Dicer accumulation is conserved in mammals. Dicer depletion causes spontaneous DNA damage and delays DNA repair. Taken together, we place Dicer in context of the DDR by demonstrating DNA damage-inducible phospho-switch that causes localised processing of nuclear dsRNA by p-Dicer to promote DNA repair.
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Overall design |
We have analysed ChIP samples from damaged and non-damaged cells, using an anti-Dicer antibody. Non-damaged sample serves as physiological control.
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Contributor(s) |
Burger K, Schlackow M, Hester SS, Mohammed S, Gullerova M |
Citation missing |
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Submission date |
Dec 10, 2015 |
Last update date |
May 15, 2019 |
Contact name |
Monika Gullerova |
E-mail(s) |
monika.gullerova@path.ox.ac.uk
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Phone |
+44794220892
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Organization name |
University of Oxford
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Department |
Sir William Dunn School of Pathology
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Street address |
South Parks Road
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City |
Oxford |
ZIP/Postal code |
OX1 3RE |
Country |
United Kingdom |
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Platforms (1) |
GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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Samples (2) |
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Relations |
BioProject |
PRJNA305622 |
SRA |
SRP067228 |