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 a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability ( ). Regulates centrosomal microtubule nucleation . Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle ( , ). Required for FANCD2 targeting to sites of DNA damage . Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation . Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks . Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8 . Acts as a transcriptional activator .
Subcellular locations: Nucleus, Chromosome, Cytoplasm
Localizes at sites of DNA damage at double-strand breaks (DSBs); recruitment to DNA damage sites is mediated by ABRAXAS1 and the BRCA1-A complex . Translocated to the cytoplasm during UV-induced apoptosis .
Subcellular locations: Cytoplasm
Subcellular locations: Cytoplasm
Isoform 1 and isoform 3 are widely expressed. Isoform 3 is reduced or absent in several breast and ovarian cancer cell lines.