The chromatin scaffold protein SAFB1 renders chromatin permissive for DNA damage signaling

Mol Cell. 2013 Oct 24;52(2):206-20. doi: 10.1016/j.molcel.2013.08.025. Epub 2013 Sep 19.


Although the general relevance of chromatin modifications for genotoxic stress signaling, cell-cycle checkpoint activation, and DNA repair is well established, how these modifications reach initial thresholds in order to trigger robust responses remains largely unexplored. Here, we identify the chromatin-associated scaffold attachment factor SAFB1 as a component of the DNA damage response and show that SAFB1 cooperates with histone acetylation to allow for efficient γH2AX spreading and genotoxic stress signaling. SAFB1 undergoes a highly dynamic exchange at damaged chromatin in a poly(ADP-ribose)-polymerase 1- and poly(ADP-ribose)-dependent manner and is required for unperturbed cell-cycle checkpoint activation and guarding cells against replicative stress. Altogether, our data reveal that transient recruitment of an architectural chromatin component is required in order to overcome physiological barriers by making chromatin permissive for DNA damage signaling, whereas the ensuing exclusion of SAFB1 may help prevent excessive signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Blotting, Western
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Chromatin / genetics*
  • Chromatin / metabolism
  • DNA Breaks, Double-Stranded / drug effects
  • DNA Breaks, Double-Stranded / radiation effects
  • DNA Damage*
  • DNA Repair
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Histones / metabolism
  • Humans
  • Matrix Attachment Region Binding Proteins / genetics*
  • Matrix Attachment Region Binding Proteins / metabolism
  • Microscopy, Fluorescence
  • Models, Genetic
  • Mutagenicity Tests
  • Nuclear Matrix-Associated Proteins / genetics*
  • Nuclear Matrix-Associated Proteins / metabolism
  • Phosphorylation
  • Poly Adenosine Diphosphate Ribose / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism
  • RNA Interference
  • Receptors, Estrogen / genetics*
  • Receptors, Estrogen / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics*


  • Chromatin
  • H2AX protein, human
  • Histones
  • Matrix Attachment Region Binding Proteins
  • Nuclear Matrix-Associated Proteins
  • Receptors, Estrogen
  • SAFB protein, human
  • Green Fluorescent Proteins
  • Poly Adenosine Diphosphate Ribose
  • Poly(ADP-ribose) Polymerases