例如:"lncRNA", "apoptosis", "WRKY"

PARP-1 Activation Directs FUS to DNA Damage Sites to Form PARG-Reversible Compartments Enriched in Damaged DNA.

Cell Rep. 2019 May 07;27(6):1809-1821.e5
Anastasia S Singatulina 1 , Loic Hamon 2 , Maria V Sukhanova 3 , Bénédicte Desforges 2 , Vandana Joshi 2 , Ahmed Bouhss 2 , Olga I Lavrik 4 , David Pastré 5
Anastasia S Singatulina 1 , Loic Hamon 2 , Maria V Sukhanova 3 , Bénédicte Desforges 2 , Vandana Joshi 2 , Ahmed Bouhss 2 , Olga I Lavrik 4 , David Pastré 5
+ et al

[No authors listed]

Author information
  • 1 SABNP, Univ Evry, INSERM U1204, Université Paris-Saclay, 91025 Evry, France; Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia.
  • 2 SABNP, Univ Evry, INSERM U1204, Université Paris-Saclay, 91025 Evry, France.
  • 3 Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia.
  • 4 Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia; Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia. Electronic address: lavrik@niboch.nsc.ru.
  • 5 SABNP, Univ Evry, INSERM U1204, Université Paris-Saclay, 91025 Evry, France. Electronic address: david.pastre@univ-evry.fr.

摘要


synthesizes long poly(ADP-ribose) chains (PAR) at DNA damage sites to recruit DNA repair factors. Among proteins relocated on damaged DNA, the RNA-binding protein FUS is one of the most abundant, raising the issue about its involvement in DNA repair. Here, we reconstituted the system in vitro and analyzed at the single-molecule level the role of FUS. We demonstrate successively the dissociation of FUS from mRNA, its recruitment at DNA damage sites through its binding to PAR, and the assembly of damaged DNA-rich compartments. PARG, an enzyme family that hydrolyzes PAR, is sufficient to dissociate damaged DNA-rich compartments in vitro and initiates the nucleocytoplasmic shuttling of FUS in cells. We anticipate that, consistent with previous models, FUS facilitates DNA repair through the transient compartmentalization of DNA damage sites. The nucleocytoplasmic shuttling of FUS after the PARG-mediated compartment dissociation may participate in the formation of cytoplasmic FUS aggregates.

KEYWORDS: DNA repair, RNA-binding proteins, atomic force microscopy, cancer, liquid-liquid phase separation, neurodegenerative disease, poly(ADP-ribose), poly(ADP-ribose) polymerase 1