The RNA-binding Protein Fused in Sarcoma (FUS) Functions Downstream of Poly(ADP-ribose) Polymerase (PARP) in Response to DNA Damage
| Autor: | Anthony T. Trinh, Adam S. Mastrocola, Sang Hwa Kim, Lance A. Rodenkirch, Randal S. Tibbetts |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Genome instability
Poly Adenosine Diphosphate Ribose DNA Repair DNA repair DNA damage Poly ADP ribose polymerase DNA and Chromosomes Biochemistry Genomic Instability chemistry.chemical_compound Cell Line Tumor Humans DNA Breaks Double-Stranded Molecular Biology Polymerase biology Lasers Cell Biology Molecular biology Protein Structure Tertiary chemistry biology.protein RNA-Binding Protein FUS Poly(ADP-ribose) Polymerases Homologous recombination DNA |
| Zdroj: | Journal of Biological Chemistry. 288:24731-24741 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m113.497974 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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