The Landscape of BRCA1-Associated Post-Translational Modifications

Abstract

The BRCA1-BARD1 complex is a vital protein that promotes homologous recombination, acting through its E3 ubiquitin ligase activity. Although ubiquitination remains its only confirmed enzymatic function, emerging evidence suggests that the complex influences a broad range of post-translational modifications (PTMs), including methylation, phosphorylation, acetylation, and PARylation, involving other proteins. This review examines findings from various eukaryotic biological models to elucidate how BRCA1 regulates key PTMs. We explore how BRCA1 shapes chromatin architecture by modulating key PTMs such as ubiquitination, methylation, and acetylation. While BRCA1-driven changes in methylation appear to have widespread effects throughout the cell, its influence on ubiquitination and acetylation tends to be more region- or site-specific. Furthermore, this review discusses BRCA1's role in modifying specific target proteins, such as PLK-1, Aurora A, and p53, and explores its involvement in non-ubiquitin PTMs. Beyond its well-established role in DNA repair, BRCA1 also contributes to other cellular processes involving non-ubiquitin PTMs, such as in meiotic sex chromosome inactivation, which is also detailed in this review. Collectively, this review expands the functional landscape of BRCA1 beyond DNA repair, providing new insights into its regulatory impact across various post-translational pathways.