Yeast Bromodomain Factor 1 and Its Human Homolog TAF1 Play Conserved Roles in Promoting Homologous Recombination

• Published in: Advanced science 2021-08, Vol.8 (15), p.e2100753-n/a
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Bromodomain Factor 1 (Bdf1); Cancer; Cell cycle; DNA damage; Genomes; Genomic Instability - genetics; histone acetylation; Histone Acetyltransferases - genetics; homologous recombination; Homologous Recombination - genetics; Humans; Phosphorylation; Proteins; Recombinational DNA Repair - genetics; Replication Protein A (RPA); Roles; Saccharomyces cerevisiae Proteins - genetics; TAF1; TATA-Binding Protein Associated Factors - genetics; Transcription Factor TFIID - genetics; Transcription Factors - genetics; Yeast
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202100753

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. How the bromodomain (BRD) proteins, readers of acetyl‐lysines, regulate DNA repair and genome stability remains partially understood. Here, a conserved function of the yeast Bromodomain Factor 1 (Bdf1) and its human counterpart TAF1 is shown in promoting DNA double‐stranded break repair by the homologous recombination pathway via physically facilitating Replication Protein A (RPA) loading on ssDNA with dispersed histones at break ends.