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image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
Nature Structural & Molecular Biology
Article . 2009 . Peer-reviewed
License: Springer TDM
Data sources: Crossref
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A macrodomain-containing histone rearranges chromatin upon sensing PARP1 activation

Authors: Timinszky, G; Till, S; Hassa, P O; Hothorn, M; Kustatscher, G; Nijmeijer, B; Colombelli, J; +5 Authors

A macrodomain-containing histone rearranges chromatin upon sensing PARP1 activation

Abstract

Poly-ADP-ribosylation is a post-translational modification catalyzed by PARP enzymes with roles in transcription and chromatin biology. Here we show that distinct macrodomains, including those of histone macroH2A1.1, are recruited to sites of PARP1 activation induced by laser-generated DNA damage. Chemical PARP1 inhibitors, PARP1 knockdown and mutation of ADP-ribose-binding residues in macroH2A1.1 abrogate macrodomain recruitment. Notably, histone macroH2A1.1 senses PARP1 activation, transiently compacts chromatin, reduces the recruitment of DNA damage factor Ku70-Ku80 and alters gamma-H2AX patterns, whereas the splice variant macroH2A1.2, which is deficient in poly-ADP-ribose binding, does not mediate chromatin rearrangements upon PARP1 activation. The structure of the macroH2A1.1 macrodomain in complex with ADP-ribose establishes a poly-ADP-ribose cap-binding function and reveals conformational changes in the macrodomain upon ligand binding. We thus identify macrodomains as modules that directly sense PARP activation in vivo and establish macroH2A histones as dynamic regulators of chromatin plasticity.

Country
Switzerland
Keywords

Models, Molecular, Poly Adenosine Diphosphate Ribose, Amino Acid Motifs, Poly (ADP-Ribose) Polymerase-1, 10226 Department of Molecular Mechanisms of Disease, Chromatin, Protein Structure, Tertiary, Enzyme Activation, Histones, 1315 Structural Biology, 1312 Molecular Biology, Humans, 570 Life sciences; biology, Poly(ADP-ribose) Polymerases, RNA Processing, Post-Transcriptional, Protein Structure, Quaternary, DNA Damage, HeLa Cells, Protein Binding

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
377
Top 1%
Top 1%
Top 1%
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