1. Academic Validation
  2. BRD4 promotes resection and homology-directed repair of DNA double-strand breaks

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

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. longdt@musc.edu.
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.

Figures
Products