FUS RRM regulates poly(ADP-ribose) levels after transcriptional arrest and PARP-1 activation on DNA damage
Résumé
PARP-1 activation at DNA damage sites leads to the synthesis of long poly(ADP-ribose) (PAR) chains, which
serve as a signal for DNA repair. Here we show that FUS, an RNA-binding protein, is specifically directed to
PAR through its RNA recognition motif (RRM) to increase PAR synthesis by PARP-1 in HeLa cells after genotoxic
stress. Using a structural approach, we also identify specific residues located in the FUS RRM, which
can be PARylated by PARP-1 to control the level of PAR synthesis. Based on the results of this work, we propose
a model in which, following a transcriptional arrest that releases FUS from nascent mRNA, FUS can be
recruited by PARP-1 activated by DNA damage to stimulate PAR synthesis. We anticipate that this model
offers new perspectives to understand the role of FET proteins in cancers and in certain neurodegenerative
diseases such as amyotrophic lateral sclerosis.
Domaines
Sciences du Vivant [q-bio]| Origine | Fichiers éditeurs autorisés sur une archive ouverte |
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