Nucleolar exit of RNF8 and BRCA1 in response to DNA damage.
The induction of DNA double-strand breaks (DSBs) elicits a plethora of responses that redirect many cellular functions to the vital task of repairing the injury, collectively known as the DNA damage response (DDR). We have found that, in the absence of DNA damage, the DSB repair factors RNF8 and BRCA1 are associated with the nucleolus. Shortly after exposure of cells to γ-radiation, RNF8 and BRCA1 translocated from the nucleolus to damage foci, a traffic that was reverted several hours after the damage. RNF8 interacted through its FHA domain with the ribosomal protein RPSA, and knockdown of RPSA caused a depletion of nucleolar RNF8 and BRCA1, suggesting that the interaction of RNF8 with RPSA is critical for the nucleolar localization of these DDR factors. Knockdown of RPSA or RNF8 impaired bulk protein translation, as did γ-irradiation, the latter being partially countered by overexpression of exogenous RNF8. Our results suggest that RNF8 and BRCA1 are anchored to the nucleolus through reversible interactions with RPSA and that, in addition to its known functions in DDR, RNF8 may play a role in protein synthesis, possibly linking the nucleolar exit of this factor to the attenuation of protein synthesis in response to DNA damage.
Department of Cell Biology, Molecular Biology Institute of Barcelona, CSIC, Barcelona Science Park, Helix Building, Baldiri Reixac 15-21, 08028 Barcelona, Spain.
Marta
M
Guerra-Rebollo
Francesca
F
Mateo
Kristin
K
Franke
Michael S Y
MS
Huen
Fernando
F
Lopitz-Otsoa
Manuel S
MS
Rodríguez
Vanessa
V
Plans
Timothy M
TM
Thomson
D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D002466:Cell Nucleolus / Q000378:metabolism*; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D017474:Receptors, Laminin / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D004268:DNA-Binding Proteins; C486521:RNF8 protein, human; C510624:RPSA protein, human; D017474:Receptors, Laminin; D012269:Ribosomal Proteins; D044767:Ubiquitin-Protein Ligases