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Histone demethylase KDM5A regulates the ZMYND8-NuRD chromatin remodeler to promote DNA repair.

ABSTRACT: Upon DNA damage, histone modifications are dynamically reshaped to accommodate DNA damage signaling and repair within chromatin. In this study, we report the identification of the histone demethylase KDM5A as a key regulator of the bromodomain protein ZMYND8 and NuRD (nucleosome remodeling and histone deacetylation) complex in the DNA damage response. We observe KDM5A-dependent H3K4me3 demethylation within chromatin near DNA double-strand break (DSB) sites. Mechanistically, demethylation of H3K4me3 is required for ZMYND8-NuRD binding to chromatin and recruitment to DNA damage. Functionally, KDM5A deficiency results in impaired transcriptional silencing and repair of DSBs by homologous recombination. Thus, this study identifies a crucial function for KDM5A in demethylating H3K4 to allow ZMYND8-NuRD to operate within damaged chromatin to repair DSBs.

SUBMITTER: Gong F

PROVIDER: S-EPMC5496618 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Histone demethylase KDM5A regulates the ZMYND8-NuRD chromatin remodeler to promote DNA repair.

Gong Fade F Clouaire Thomas T Aguirrebengoa Marion M Legube Gaëlle G Miller Kyle M KM

The Journal of cell biology 20170601 7

Upon DNA damage, histone modifications are dynamically reshaped to accommodate DNA damage signaling and repair within chromatin. In this study, we report the identification of the histone demethylase KDM5A as a key regulator of the bromodomain protein ZMYND8 and NuRD (nucleosome remodeling and histone deacetylation) complex in the DNA damage response. We observe KDM5A-dependent H3K4me3 demethylation within chromatin near DNA double-strand break (DSB) sites. Mechanistically, demethylation of H3K4 ...[more]

PMID: 28572115

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