The Chromatin Scaffold Protein SAFB1 Renders Chromatin Permissive for DNA Damage Signaling
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The Chromatin Scaffold Protein SAFB1 Renders Chromatin Permissive for DNA Damage Signaling. / Altmeyer, Matthias; Toledo Lazaro, Luis Ignacio; Gudjonsson, Thorkell; Grøfte, Merete; Rask, Maj-Britt; Lukas, Claudia; Akimov, Vyacheslav; Blagoev, Blagoy; Bartek, Jiri; Lukas, Jiri.
In: Molecular Cell, Vol. 52, No. 2, 24.10.2013, p. 206-220.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 52
SP - 206
EP - 220
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 2
ER -
ID: 57420635