Article
BRCA2 promotes DNA-RNA hybrid resolution by DDX5 helicase at DNA breaks to facilitate their repair
Author/s | Sessa, Gaetana
Gómez González, Belén María Silva, Sonia Pérez Calero, Carmen Beaurepere, Romane Barroso Ceballos, Sonia Inés ![]() ![]() ![]() ![]() Martineau, Sylvain Martin, Charlotte A. Ehlén, Åsa Martínez, Juan S. Lombard, Bérangére Loew, Damarys Vagner, Stéphan Aguilera López, Andrés ![]() ![]() ![]() ![]() ![]() ![]() ![]() Carreira, Aura |
Department | Universidad de Sevilla. Departamento de Genética |
Publication Date | 2021 |
Deposit Date | 2021-05-27 |
Published in |
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Abstract | The BRCA2 tumor suppressor is a DNA double-strand break (DSB) repair factor essential for maintaining genome integrity. BRCA2-deficient cells spontaneously accumulate DNA-RNA hybrids, a known source of genome instability. ... The BRCA2 tumor suppressor is a DNA double-strand break (DSB) repair factor essential for maintaining 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 protein. 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-unwinding activity of DDX5 helicase. An impaired BRCA2-DDX5 interaction, as observed in cells expressing the breast cancer variant BRCA2-T207A, reduces the association of DDX5 with DNA-RNA hybrids, decreases the number of RPA foci, and alters the kinetics of appearance of RAD51 foci upon irradiation. Our findings are consistent with DNA-RNA hybrids constituting an impediment for the repair of DSBs by homologous recombination and reveal BRCA2 and DDX5 as active players in their removal. |
Project ID. | ANR-17-CE12-0016
![]() INCa- DGOS_8706 ![]() ERC2014 AdG669898 TARLOOP ![]() BFU2016-75058-P ![]() |
Citation | Sessa, G., Gómez González, B.M., Silva, S., Pérez Calero, C., Beaurepere, R., Barroso Ceballos, S.I.,...,Carreira, A. (2021). BRCA2 promotes DNA-RNA hybrid resolution by DDX5 helicase at DNA breaks to facilitate their repair. EMBO Journal, 40 (7), e106018. |
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