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CHD7- and HDAC1/2-dependent chromatin remodeling activities cooperate to promote DNA double-strand break repair

ABSTRACT: The DNA double-strand break (DSB) response is a multi-step process that requires chromatin reorganization at each stage. 53BP1 is a nodal point in this response as it directs chromatin-based DSB repair. However, how chromatin reorganization impacts DSB repair upstream of 53BP1 is not fully understood. Here we reveal that Chromodomain Helicase DNA Binding Protein 7 (CHD7) rapidly recruits to damaged chromatin in a poly(ADP-ribose) polymerase 1 (PARP1)-dependent manner. CHD7 facilitates chromatin relaxation and the loading of canonical non-homologous end-joining (cNHEJ) factors, while restraining 53BP1 accumulation at DSBs. Moreover, CHD7 physically associates with HDAC1/2, thereby recruiting this complex to DNA breaks independently of its chromatin remodeling activity. HDAC1/2 promote histone H4 de-acetylation and chromatin re-compaction to prevent supraphysiological retention of cNHEJ factors at DBSs. Thus, the cooperation between distinct yet coordinated chromatin remodeling activities driven by CHD7 and HDAC1/2 ensures proper assembly dynamics of the cNHEJ machinery and efficient DSB repair.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Alfred Vertegaal

LAB HEAD: Alfred C.O. Vertegaal

PROVIDER: PXD014339 | Pride | 2020-08-28

REPOSITORIES: Pride

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2016-12-12 | PXD004912 | Pride

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