Artículo
BRCA2 promotes DNA-RNA hybrid resolution by DDX5 helicase at DNA breaks to facilitate their repair
Autor/es | Sessa, Gaetana
Gómez González, Belén 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 |
Departamento | Universidad de Sevilla. Departamento de Genética |
Fecha de publicación | 2021 |
Fecha de depósito | 2021-05-27 |
Publicado en |
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Resumen | 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. |
Identificador del proyecto | ANR-17-CE12-0016
INCa- DGOS_8706 ERC2014 AdG669898 TARLOOP BFU2016-75058-P |
Cita | 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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2021.EMBO J-Sessa.pdf | 3.972Mb | [PDF] | Ver/ | |