Department of Biochemistry, University of Washington School of Medicine, Seattle, WA, USA.
Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Trends Biochem Sci. 2022 Jul;47(7):582-595. doi: 10.1016/j.tibs.2022.03.001. Epub 2022 Mar 26.
Mutations in BRCA1 and BARD1 predispose carriers to breast and ovarian cancers. The BRCA1 and BARD1 proteins form a heterodimeric complex (BRCA1/BARD1) that regulates many biological processes, including transcription and DNA double-stranded break repair. These functions are mediated by the only known enzymatic activity of BRCA1/BARD1 in its capacity as an E3 ubiquitin ligase and its role as a central hub for many large protein complexes. But the mechanisms by which BRCA1/BARD1 interfaces with chromatin, where it exerts its major functions, have remained unknown. Here, we review recent advancements in structural and cellular biology that have provided critical insights into how BRCA1/BARD1 serves as both a nucleosome reader and writer to facilitate transcriptional regulation and DNA repair by homologous recombination.
BRCA1 和 BARD1 的突变使携带者易患乳腺癌和卵巢癌。BRCA1 和 BARD1 蛋白形成异二聚体复合物（BRCA1/BARD1），调节许多生物学过程，包括转录和 DNA 双链断裂修复。这些功能是由 BRCA1/BARD1 作为 E3 泛素连接酶的唯一已知酶活性以及作为许多大型蛋白质复合物的中心枢纽来介导的。但是，BRCA1/BARD1 与染色质相互作用的机制，在那里它发挥其主要功能，仍然未知。在这里，我们回顾了结构和细胞生物学的最新进展，这些进展为 BRCA1/BARD1 如何作为核小体阅读器和写入器提供了关键的见解，以促进转录调节和同源重组的 DNA 修复。
