BRCA1 Protein, Human

BRCA1 is an E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The BRCA1-BARD1 heterodimer coordinates diverse cellular pathways such as DNA damage repair, ubiquitination, and transcriptional regulation to maintain genomic stability. Additionally, it regulates centrosomal microtubule nucleation and is required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and G2 phase. BRCA1 is also involved in targeting FANCD2 to sites of DNA damage, inhibits lipid synthesis by binding to inactive phosphorylated ACACA, and contributes to homologous recombination repair (HRR) through its interaction with PALB2. As part of the BRCA1-RBBP8 complex, it regulates CHEK1 activation and controls the G2/M checkpoint following DNA damage via BRCA1-mediated ubiquitination of RBBP8. BRCA1 also functions as a transcriptional activator.