Publication: BRCA2 promotes DNA-RNA hybrid resolution by DDX5 helicase at DNA breaks to facilitate their repair‡.
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Date
2021-02-26
Authors
Sessa, Gaetana
Gómez-González, Belén
Silva, Sonia
Pérez-Calero, Carmen
Beaurepere, Romane
Barroso, Sonia
Martineau, Sylvain
Martin, Charlotte
Ehlén, Åsa
Martínez, Juan S
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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. 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.
Description
MeSH Terms
BRCA2 Protein
Cell Line, Tumor
DEAD-box RNA Helicases
DNA Breaks, Double-Stranded
HEK293 Cells
Humans
Nucleic Acid Heteroduplexes
Protein Binding
Recombinational DNA Repair
Cell Line, Tumor
DEAD-box RNA Helicases
DNA Breaks, Double-Stranded
HEK293 Cells
Humans
Nucleic Acid Heteroduplexes
Protein Binding
Recombinational DNA Repair
DeCS Terms
CIE Terms
Keywords
BRCA2, DNA double-strand breaks, DNA-RNA hybrids, R-loops, homologous recombination