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Acetylation blocks DNA damage-induced chromatin ADP-ribosylation.

Glen Liszczak, Katharine L Diehl, Geoffrey P Dann, Tom W Muir
Nature Chemical Biology 2018 September
Recent studies report serine ADP-ribosylation on nucleosomes during the DNA damage response. We unveil histone H3 serine 10 as the primary acceptor residue for chromatin ADP-ribosylation and find that specific histone acetylation marks block this activity. Our results provide a molecular explanation for the well-documented phenomenon of rapid deacetylation at DNA damage sites and support the combinatorial application of PARP and HDAC inhibitors for the treatment of PARP-dependent cancers.

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