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

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  • John K. Barrows

    (Medical University of South Carolina)

  • Baicheng Lin

    (Medical University of South Carolina)

  • Colleen E. Quaas

    (Medical University of South Carolina)

  • George Fullbright

    (Medical University of South Carolina)

  • Elizabeth N. Wallace

    (Medical University of South Carolina)

  • David T. Long

    (Medical University of South Carolina)

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.

Suggested Citation

  • John K. Barrows & Baicheng Lin & Colleen E. Quaas & George Fullbright & Elizabeth N. Wallace & David T. Long, 2022. "BRD4 promotes resection and homology-directed repair of DNA double-strand breaks," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30787-6
    DOI: 10.1038/s41467-022-30787-6
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