BRCA2 promotes DNA-RNA hybrid resolution by DDX5 helicase at DNA breaks to facilitate their repair‡.
BRCA2
DNA double-strand breaks
DNA-RNA hybrids
R-loops
homologous recombination
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
01 04 2021
01 04 2021
Historique:
revised:
22
01
2021
received:
23
06
2020
accepted:
25
01
2021
pubmed:
27
2
2021
medline:
3
4
2022
entrez:
26
2
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33634895
doi: 10.15252/embj.2020106018
pmc: PMC8013831
doi:
Substances chimiques
BRCA2 Protein
0
BRCA2 protein, human
0
Nucleic Acid Heteroduplexes
0
Ddx5 protein, human
EC 3.6.1.-
DEAD-box RNA Helicases
EC 3.6.4.13
Banques de données
GEO
['GSE150163']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e106018Informations de copyright
© 2021 The Authors.
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