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DNA damage induces nuclear actin filament assembly by Formin -2 and Spire-½ that promotes efficient DNA repair. [corrected].

Brittany J Belin | Terri Lee | R Dyche Mullins
eLife | 2015

Actin filaments assemble inside the nucleus in response to multiple cellular perturbations, including heat shock, protein misfolding, integrin engagement, and serum stimulation. We find that DNA damage also generates nuclear actin filaments-detectable by phalloidin and live-cell actin probes-with three characteristic morphologies: (i) long, nucleoplasmic filaments; (ii) short, nucleolus-associated filaments; and (iii) dense, nucleoplasmic clusters. This DNA damage-induced nuclear actin assembly requires two biologically and physically linked nucleation factors: Formin-2 and Spire-1/Spire-2. Formin-2 accumulates in the nucleus after DNA damage, and depletion of either Formin-2 or actin's nuclear import factor, importin-9, increases the number of DNA double-strand breaks (DSBs), linking nuclear actin filaments to efficient DSB clearance. Nuclear actin filaments are also required for nuclear oxidation induced by acute genotoxic stress. Our results reveal a previously unknown role for nuclear actin filaments in DNA repair and identify the molecular mechanisms creating these nuclear filaments.

Pubmed ID: 26287480

Research resources used in this publication

None found

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Associated grants

  • Agency: NIA NIH HHS, United States
    Id: F31 AG039147
  • Agency: NIGMS NIH HHS, United States
    Id: GM061010
  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM118119
  • Agency: NIGMS NIH HHS, United States
    Id: GM079556
  • Agency: Howard Hughes Medical Institute, United States
  • Agency: NIA NIH HHS, United States
    Id: 5F31AG39147-2
  • Agency: NIGMS NIH HHS, United States
    Id: R13 GM085967

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