XB-ART-59146
Nat Commun
2022 May 31;131:3016. doi: 10.1038/s41467-022-30787-6.
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BRD4 promotes resection and homology-directed repair of DNA double-strand breaks.
Barrows JK
,
Lin B
,
Quaas CE
,
Fullbright G
,
Wallace EN
,
Long DT
.
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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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Genes referenced: brd4
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