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BRD4 promotes resection and homology-directed repair of DNA double-strand breaks.

ABSTRACT: Double-strand breaks (DSBs) are one of the most toxic forms of DNA damage and represent a major source of genomic instability. Members of the bromodomain and extra-terminal (BET) protein family are characterized as epigenetic readers that regulate gene expression. However, evidence suggests that BET proteins also play a more direct role in DNA repair. Here, we establish a cell-free system using Xenopus egg extracts to elucidate the gene expression-independent functions of BET proteins in DSB repair. We identify the BET protein BRD4 as a critical regulator of homologous recombination and describe its role in stimulating DNA processing through interactions with the SWI/SNF chromatin remodeling complex and resection machinery. These results establish BRD4 as a multifunctional regulator of chromatin binding that links transcriptional activity and homology-directed repair.

SUBMITTER: Barrows JK

PROVIDER: S-EPMC9156784 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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BRD4 promotes resection and homology-directed repair of DNA double-strand breaks.

Barrows John K JK Lin Baicheng B Quaas Colleen E CE Fullbright George G Wallace Elizabeth N EN Long David T DT

Nature communications 20220531 1

Double-strand breaks (DSBs) are one of the most toxic forms of DNA damage and represent a major source of genomic instability. Members of the bromodomain and extra-terminal (BET) protein family are characterized as epigenetic readers that regulate gene expression. However, evidence suggests that BET proteins also play a more direct role in DNA repair. Here, we establish a cell-free system using Xenopus egg extracts to elucidate the gene expression-independent functions of BET proteins in DSB rep ...[more]

PMID: 35641523

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