DNA damage induces nuclear actin filament assembly by Formin-2 and Spire-1/2 that promotes efficient DNA repair
DNA damage induces nuclear actin filament assembly by Formin-2 and Spire-1/2 that promotes efficient DNA repair
Date
2015-08-19
Authors
Belin, Brittany J.
Lee, Terri
Mullins, R. Dyche
Lee, Terri
Mullins, R. Dyche
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DOI
10.7554/eLife.07735
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Abstract
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.
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© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in eLife 4 (2015): e07735, doi:10.7554/eLife.07735.
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eLife 4 (2015): e07735