|
|
GEO help: Mouse over screen elements for information. |
|
Status |
Public on Feb 26, 2021 |
Title |
BRCA2 promotes DNA-RNA hybrid resolution by DDX5 helicase at DNA breaks to facilitate their repair |
Organism |
Homo sapiens |
Experiment type |
Other
|
Summary |
The BRCA2 tumor suppressor is a DNA double-strand break repair factor essential to maintain genome integrity. BRCA2-deficient cells spontaneously accumulate DNA-RNA hybrids, a known source of genome instability. However, the specific role of BRCA2 on these structures remains poorly understood. Here we identified the DEAD-box RNA helicase DDX5 as a BRCA2 interacting partner. We show that DDX5 associates with DNA-RNA hybrids that form in the vicinity of DSBs and this association is enhanced by BRCA2. Notably, BRCA2 stimulates the DNA-RNA hybrid helicase activity of DDX5. Impaired BRCA2-DDX5 interaction, as observed in cells bearing the breast cancer variant BRCA2-T207A, reduces DDX5 association with DSBs, decreases the number of RPA foci upon irradiation and impairs RAD51 repair foci formation. Our findings are consistent with DNA-RNA hybrids being an impediment for the repair of DSBs by homologous recombination and reveal BRCA2 and DDX5 as active players in their removal.
|
|
|
Overall design |
Genome-wide inspection of RNA-DNA hybrids accumulation in siC control and DDX5-depleted (siDDX5) K562 cells
|
|
|
Contributor(s) |
Sessa G, Gómez-González B, Silva S, Pérez-Calero C, Beaurepere R, Barroso S, Martineau S, Martin C, Ehlén Å, Martínez JS, Lombard B, Loew D, Vagner S, Aguilera A, Carreira A |
Citation(s) |
33634895 |
|
Submission date |
May 08, 2020 |
Last update date |
Mar 19, 2021 |
Contact name |
Andrés Aguilera |
Organization name |
CABIMER, Universidad de Sevilla
|
Department |
Genome BIology
|
Lab |
Genome Instability & Cancer
|
Street address |
Av. Américo Vespucio 24
|
City |
Seville |
ZIP/Postal code |
41092 |
Country |
Spain |
|
|
Platforms (1) |
GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
Samples (4)
|
|
Relations |
BioProject |
PRJNA631281 |
SRA |
SRP260830 |
Supplementary file |
Size |
Download |
File type/resource |
GSE150163_RAW.tar |
292.0 Mb |
(http)(custom) |
TAR (of BIGWIG) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
|
|
|
|
|