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Title: The RNA-binding protein fused in sarcoma (FUS) functions downstream of poly(ADP-ribose) polymerase (PARP) in response to DNA damage.

Authors: Mastrocola, Adam S; Kim, Sang Hwa; Trinh, Anthony T; Rodenkirch, Lance A; Tibbetts, Randal S

Published In J Biol Chem, (2013 Aug 23)

Abstract: The list of factors that participate in the DNA damage response to maintain genomic stability has expanded significantly to include a role for proteins involved in RNA processing. Here, we provide evidence that the RNA-binding protein fused in sarcoma/translocated in liposarcoma (FUS) is a novel component of the DNA damage response. We demonstrate that FUS is rapidly recruited to sites of laser-induced DNA double-strand breaks (DSBs) in a manner that requires poly(ADP-ribose) (PAR) polymerase activity, but is independent of ataxia-telangiectasia mutated kinase function. FUS recruitment is mediated by the arginine/glycine-rich domains, which interact directly with PAR. In addition, we identify a role for the prion-like domain in promoting accumulation of FUS at sites of DNA damage. Finally, depletion of FUS diminished DSB repair through both homologous recombination and nonhomologous end-joining, implicating FUS as an upstream participant in both pathways. These results identify FUS as a new factor in the immediate response to DSBs that functions downstream of PAR polymerase to preserve genomic integrity.

PubMed ID: 23833192 Exiting the NIEHS site

MeSH Terms: Cell Line, Tumor; DNA Breaks, Double-Stranded*; DNA Repair/physiology*; Genomic Instability/physiology*; Humans; Lasers/adverse effects; Poly Adenosine Diphosphate Ribose/genetics; Poly Adenosine Diphosphate Ribose/metabolism; Poly(ADP-ribose) Polymerases/genetics; Poly(ADP-ribose) Polymerases/metabolism*; Protein Structure, Tertiary; RNA-Binding Protein FUS/genetics; RNA-Binding Protein FUS/metabolism*

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