In spite of the push to identify modifiers of BRCAness, it still remains unclear how tumor suppressor BRCA1 is lost in breast cancers in the absence of genetic or epigenetic aberrations. Mounting evidence indicates Cthat the transforming acidic coiled-coil 3 (TACO) plays an important role in the centrosome-microtubule network during mitosis and gene expression, and that deregulation of TACO is associated with breast cancer. However, the molecular mechanisms by which TACO contributes to breast cancer development have yet to be elucidated. Herein, we found that high levels of TACO in human mammary epithelial cells can cause genomic instability possibly in part through destabilizing BRCA1. We also found that high levels of TACO inhibited the interaction between BRCA1 and BARD1, thus subsequently allowing the BARD1-uncoupled BRCA1 to be destabilized by ubiquitin-mediated proteosomal pathway. Moreover, there is an inverse correlation between TACO and BRCA1 expression in breast cancer tissues. Overall, our findings provide a new insight into the role of TACO in genomic instability and breast tumorigenesis. (C) 2018 Elsevier Inc. All rights reserved.