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DNA damage induces nuclear actin filament assembly by formin-2 and Spire-1/2 that promotes efficient DNA repair

  1. Brittany J Belin
  2. Terri Lee
  3. R Dyche Mullins  Is a corresponding author
  1. University of California, San Francisco, United States
Research Article
  • Cited 76
  • Views 6,646
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Cite this article as: eLife 2015;4:e07735 doi: 10.7554/eLife.07735

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.

Article and author information

Author details

  1. Brittany J Belin

    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Terri Lee

    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. R Dyche Mullins

    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States
    For correspondence
    Dyche.Mullins@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Pekka Lappalainen, University of Helsinki, Finland

Publication history

  1. Received: March 27, 2015
  2. Accepted: August 12, 2015
  3. Accepted Manuscript published: August 19, 2015 (version 1)
  4. Version of Record published: September 22, 2015 (version 2)

Copyright

© 2015, Belin et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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