FUS RRM regulates poly(ADP-ribose) levels after transcriptional arrest and PARP-1 activation on DNA damage - Université d'Évry Access content directly
Journal Articles Cell Reports Year : 2023

FUS RRM regulates poly(ADP-ribose) levels after transcriptional arrest and PARP-1 activation on DNA damage

Abstract

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.
Fichier principal
Vignette du fichier
PIIS2211124723012111.pdf (8.82 Mo) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Licence : CC BY - Attribution

Dates and versions

hal-04231448 , version 1 (08-11-2023)

Identifiers

Cite

Evgeniya Mamontova, Marie-Jeanne Clément, Maria Sukhanova, Vandana Joshi, Ahmed Bouhss, et al.. FUS RRM regulates poly(ADP-ribose) levels after transcriptional arrest and PARP-1 activation on DNA damage. Cell Reports, 2023, 42 (10), pp.113199. ⟨10.1016/j.celrep.2023.113199⟩. ⟨hal-04231448⟩
48 View
3 Download

Altmetric

Share

Gmail Facebook X LinkedIn More