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

TY - JOUR

T1 - The Chromatin Scaffold Protein SAFB1 Renders Chromatin Permissive for DNA Damage Signaling

AU - Altmeyer, Matthias

AU - Toledo Lazaro, Luis Ignacio

AU - Gudjonsson, Thorkell

AU - Grøfte, Merete

AU - Rask, Maj-Britt

AU - Lukas, Claudia

AU - Akimov, Vyacheslav

AU - Blagoev, Blagoy

AU - Bartek, Jiri

AU - Lukas, Jiri

N1 - Copyright © 2013 Elsevier Inc. All rights reserved.

PY - 2013/10/24

Y1 - 2013/10/24

N2 - 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.

AB - 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.

U2 - 10.1016/j.molcel.2013.08.025

DO - 10.1016/j.molcel.2013.08.025

M3 - Journal article

C2 - 24055346

SN - 1097-2765

VL - 52

SP - 206

EP - 220

JO - Molecular Cell

JF - Molecular Cell

IS - 2

ER -