The BARD1 gene (BRCA1-associated RING domain 1) is a tumour suppressor coding for the protein BARD1, an important protein binding and stabilising the BRCA1 protein. BARD1 and BRCA1 form a stable heterodimer via their RING finger domains, while the respective monomers are unstable. BRCA1 (breast cancer type 1 susceptibility protein) is normally responsible for repairing DNA, whereas BRCA1 mutations have been shown to increase the risk for breast cancer. The BARD1-BRCA1 structural association, and the fact that cancer-associated mutations of BRCA1 and 2 have been found in up to 40-50% of inherited cancers, compared to only a few cancer-associated mutations being found for BARD1, led to the currently accepted hypothesis that BARD1 acts as an accessory protein for BRCA1 functions.
However, BARD1, independently of BRCA1, plays a role in mitosis, as recent results showed that BARD1 is specifically required for completion of cytokinesis. BARD1 depletion by siRNA leads to a phenotype reminiscent of upregulation of the mitotic kinase Aurora B, depletion of TACC1, or depletion of BRCA2. BARD1, like BRCA2, localizes to the midbody at cytokinesis and depletion of BARD1, like BRCA2, leads to cell cycle arrest at cytokinesis. Specifically, the BARD1β isoform, but not “normal” BARD1, forms complexes with Aurora B and BRCA2, suggesting that these proteins act in a common pathway.
However, cancer cells express a number of aberrant BARD1 molecules generated by alternative splicing that antagonize the functions of “normal” BARD1 and BRCA1 functions and act as drivers of oncogenesis,. A combination of aberrant BARD1 molecules is specific for different cancers,. BARD1 mutations promoting alternative splicing have now been identified in non-coding and coding regions that predispose to cancer,. Therefore, it is now suggested that BARD1 epitopes are novel and specific biomarkers for multiple cancers.
3-dimentional structure of BARD1