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| Status |
Public on Mar 15, 2021 |
| Title |
DROSHA is recruited to DNA damage sites by the MRN complex to promote non-homologous end-joining |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The DNA damage response (DDR) is the signaling cascade that recognizes DNA double-strand breaks (DSB) and promotes their resolution via the DNA repair pathways of Non-Homologous End Joining (NHEJ) or Homologous Recombination (HR). We and others have shown that DDR activation requires DROSHA. However, whether DROSHA exerts its functions by associating with damage sites, what controls its recruitment and how DROSHA influences DNA repair, remains poorly understood. Here we show that DROSHA associates to DSBs independently from transcription. Neither H2AX, nor ATM nor DNA-PK kinase activities are required for its recruitment to break site. Rather, DROSHA interacts with RAD50 and inhibition of MRN by Mirin treatment abolishes this interaction. MRN inactivation by RAD50 knockdown or mirin treatment prevents DROSHA recruitment to DSB and, as a consequence, also 53BP1 recruitment. During DNA repair, DROSHA inactivation reduces NHEJ and boosts HR frequency. Indeed, DROSHA knockdown also increase the association of downstream HR factors such as RAD51 to DNA ends. Overall, our results demonstrate that DROSHA is recruited at DSBs by the MRN complex and direct DNA repair toward NHEJ.
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| Overall design |
gH2AX ChIP-seq, 1 replicate per condition, 2 conditions (Induced and Uninduced) DROSHA ChIP-seq, 1 replicate per condition, 2 conditions (Induced and Uninduced)
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| Contributor(s) |
Cabrini M, Roncador M, Galbiati A, Cipolla L, Maffia A, Iannelli F, Sabbioneda S, d'Adda di Fagagna F, Francia S |
| Citation(s) |
33558311 |
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| Submission date |
Feb 11, 2021 |
| Last update date |
Mar 17, 2021 |
| Contact name |
Sofia Francia |
| E-mail(s) |
sofia.francia@igm.cnr.it
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| Phone |
+39 0382 546325
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| Organization name |
Istituto di Genetica Molecolare - Consiglio Nazionale delle Ricerche (IGM-CNR)
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| Street address |
Via Abbiategrasso, 207
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| City |
Pavia |
| ZIP/Postal code |
27100 |
| Country |
Italy |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA701448 |
| SRA |
SRP305889 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE166631_RAW.tar |
1.8 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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