The Chromatin Scaffold Protein SAFB1 Renders Chromatin Permissive for DNA Damage Signaling

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

Research output: Contribution to journalJournal articleResearchpeer-review

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.
Original languageEnglish
JournalMolecular Cell
Volume52
Issue number2
Pages (from-to)206-220
ISSN1097-2765
DOIs
Publication statusPublished - 2013

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