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

  • Nat Commun. 2022 May 31;13(1):3016. doi: 10.1038/s41467-022-30787-6.
John K Barrows  1 ,  Baicheng Lin  1 ,  Colleen E Quaas  1 ,  George Fullbright  1 ,  Elizabeth N Wallace  1 ,  David T Long  2
Affiliations
  • 1. Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, 29425, USA.
  • 2. Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, 29425, USA. [email protected].
PMID: 35641523 DOI: 10.1038/s41467-022-30787-6
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.

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