| Autor: |
Lenzken, Silvia C., Levone, Brunno R., Filosa, Giuseppe, Antonaci, Marco, Conte, Francesca, Kizilirmak, Cise, Reber, Stefan, Loffreda, Alessia, Biella, Fabio, Ronchi, Antonella E., Mühlemann, Oliver, Bachi, Angela, Ruepp, Marc-David, Barabino, Silvia M.L. |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| DOI: |
10.1101/798884 |
| Popis: |
Summary RNA-binding proteins (RBPs) are emerging as important effectors of the cellular DNA damage response (DDR). Implicated in RNA metabolism and DNA repair, the RBP Fused-in-sarcoma (FUS) contains a prion-like domain (PLD) and undergoes reversible phase separation. Here, we report that liquid-liquid phase separation (LLPS) occurs at DNA damage foci and is necessary for the efficient recruitment of key DDR factors. We show that FUS co-purifies with the DDR factor KU and with SFPQ, another PLD-containing RBP implicated in DNA repair. Moreover, we demonstrate that FUS is required for 53BP1 localisation to DNA damage foci and for the correct recruitment of KU80 and NBS1 to sites of DNA damage. LLPS-deficient FUS variants impair retention of the DNA damage sensor KU at sites of DNA damage, and the recruitment of SFPQ. These findings provide a mechanistic function for FUS-dependent LLPS in the activation of the DDR and in the recruitment of DDR factors and RBPs at sites of DNA damage. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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