Open AccessYeast Bromodomain Factor 1 and Its Human Homolog TAF1 Play Conserved Roles in Promoting Homologous Recombination
Author(s) -
Peng Haoyang,
Zhang Simin,
Peng Yihan,
Zhu Shuangyi,
Zhao Xin,
Zhao Xiaocong,
Yang Shuangshuang,
Liu Guangxue,
Dong Yang,
Gan Xiaoli,
Li Qing,
Zhang Xinghua,
Pei Huadong,
Chen Xuefeng
Publication year - 2021
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202100753
Subject(s) - bromodomain , chromatin , histone , microbiology and biotechnology , replication protein a , dna repair , homologous recombination , biology , histone code , nucleosome , genetics , genome instability , chemistry , dna damage , dna , dna binding protein , gene , transcription factor
Histone acetylation is a key histone post‐translational modification that shapes chromatin structure, dynamics, and function. Bromodomain (BRD) proteins, the readers of acetyl‐lysines, are located in the center of the histone acetylation‐signaling network. How they regulate DNA repair and genome stability remains poorly understood. Here, a conserved function of the yeast Bromodomain Factor 1 (Bdf1) and its human counterpart TAF1 is reported in promoting DNA double‐stranded break repair by homologous recombination (HR). Depletion of either yeast BDF1 or human TAF1, or disruption of their BRDs impairs DNA end resection, Replication Protein A (RPA) and Rad51 loading, and HR repair, causing genome instability and hypersensitivity to DNA damage. Mechanistically, it is shown that Bdf1 preferentially binds the DNA damage‐induced histone H4 acetylation (H4Ac) via the BRD motifs, leading to its chromatin recruitment. Meanwhile, Bdf1 physically interacts with RPA, and this interaction facilitates RPA loading in the chromatin context and the subsequent HR repair. Similarly, TAF1 also interacts with H4Ac or RPA. Thus, Bdf1 and TAF1 appear to share a conserved mechanism in linking the HR repair to chromatin acetylation in preserving genome integrity.