title: RRP6/EXOSC10 is required for the repair of DNA double-strand breaks by homologous recombination.
abstract: The exosome acts on different RNA substrates and plays important roles in RNA metabolism. The fact that short non-coding RNAs are involved in the DNA damage response led us to investigate whether the exosome factor RRP6 of Drosophila melanogaster and its human ortholog EXOSC10 play a role in DNA repair. Here, we show that RRP6 and EXOSC10 are recruited to DNA double-strand breaks (DSBs) in S2 cells and HeLa cells, respectively. Depletion of RRP6/EXOSC10 does not interfere with the phosphorylation of the histone variant H2Av (Drosophila) or H2AX (humans), but impairs the recruitment of the homologous recombination factor RAD51 to the damaged sites, without affecting RAD51 levels. The recruitment of RAD51 to DSBs in S2 cells is also inhibited by overexpression of RRP6-Y361A-V5, a catalytically inactive RRP6 mutant. Furthermore, cells depleted of RRP6 or EXOSC10 are more sensitive to radiation, which is consistent with RRP6/EXOSC10 playing a role in DNA repair. RRP6/EXOSC10 can be co-immunoprecipitated with RAD51, which links RRP6/EXOSC10 to the homologous recombination pathway. Taken together, our results suggest that the ribonucleolytic activity of RRP6/EXOSC10 is required for the recruitment of RAD51 to DSBs.
authors: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden.
authors: Consuelo
authors: C
authors: Marin-Vicente
authors: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden.
authors: Judit
authors: J
authors: Domingo-Prim
authors: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden.
authors: Andrea B
authors: AB
authors: Eberle
authors: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden neus.visa@su.se.
authors: Neus
authors: N
authors: Visa
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D005095:Exoribonucleases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D063326:Exosome Multienzyme Ribonuclease Complex / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D059765:Homologous Recombination / Q000235:genetics*; D006801:Humans; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D051135:Rad51 Recombinase / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D006657:Histones; D034741:RNA, Small Interfering; C545895:Rrp6 protein, Drosophila; D051135:Rad51 Recombinase; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; C077044:EXOSC10 protein, human
keywords: DNA repair; EXOSC10; Exosome; Non-coding RNA; RAD51; RRP6