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Acetylation blocks DNA damage-induced chromatin ADP-ribosylation.

ABSTRACT: 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.

SUBMITTER: Liszczak G

PROVIDER: S-EPMC6505472 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Acetylation blocks DNA damage-induced chromatin ADP-ribosylation.

Liszczak Glen G Diehl Katharine L KL Dann Geoffrey P GP Muir Tom W TW

Nature chemical biology 20180716 9

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. ...[more]

PMID: 30013063

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