The tumor suppressor, breast cancer susceptibility gene 1 (BRCA1), plays an integral role in the maintenance of genome stability and, in particular, the cellular response to DNA damage. Here, the emerging role of BRCA1 in nonhomologous end-joining-mediated DNA repair following DNA damage will be reviewed, as well as the activation of apoptotic pathways. The control of these functions via DNA damage-induced BRCA1 shuttling will also be discussed, in particular BRCA1 shuttling induced by erlotinib and irradiation. Finally, the potential targeting of BRCA1 shuttling as a novel strategy to sensitize cells to DNA damage will be entertained. © 2010 FEBS.