RT Journal Article
T1 BRCA2 promotes DNA-RNA hybrid resolution by DDX5 helicase at DNA breaks to facilitate their repair‡.
A1 Sessa, Gaetana
A1 Gómez-González, Belén
A1 Silva, Sonia
A1 Pérez-Calero, Carmen
A1 Beaurepere, Romane
A1 Barroso, Sonia
A1 Martineau, Sylvain
A1 Martin, Charlotte
A1 Ehlén, Åsa
A1 Martínez, Juan S
A1 Lombard, Bérangère
A1 Loew, Damarys
A1 Vagner, Stephan
A1 Aguilera, Andrés
A1 Carreira, Aura
K1 BRCA2
K1 DNA double-strand breaks
K1 DNA-RNA hybrids
K1 R-loops
K1 homologous recombination
AB 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.
YR 2021
FD 2021-02-26
LK http://hdl.handle.net/10668/17243
UL http://hdl.handle.net/10668/17243
LA en
DS RISalud
RD Apr 5, 2025