BRD4 Promotes Resection and Homology-directed Repair of DNA Double-strand Breaks

Overview

Journal Nat Commun

Specialty Biology

Date 2022 May 31

PMID 35641523

Authors

John K Barrows

Baicheng Lin

Colleen E Quaas

George Fullbright

Elizabeth N Wallace

David T Long

Affiliations

Soon will be listed here.

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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