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

Matthias Altmeyer; Luis Toledo; Thorkell Gudjonsson; Merete Grøfte; Maj-Britt Rask; Claudia Lukas; Vyacheslav Akimov; Blagoy Blagoev; Jiri Bartek; Jiri Lukas

doi:10.1016/j.molcel.2013.08.025

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.

Authors

Matthias Altmeyer¹, Luis Toledo, Thorkell Gudjonsson, Merete Grøfte, Maj-Britt Rask, Claudia Lukas, Vyacheslav Akimov, Blagoy Blagoev, Jiri Bartek, Jiri Lukas

Affiliation

¹ Chromosome Stability and Dynamics Group, Department of Disease Biology, the Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.

PMID: 24055346
DOI: 10.1016/j.molcel.2013.08.025

Abstract

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*

Substances

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