The BRCA1 ubiquitin ligase and homologous recombination repair

Impairment of homologous recombination (HR), a vital process employed during repair of DNA double strand breaks and stalled DNA replication, provides a valuable opportunity for the cell to become transformed. Once transformed, the impairment turns to be a target for therapy as exemplified by the synthetic lethal strategy such as poly (ADP-ribose) polymerase (PARP) inhibitor for BRCA1/2-defective breast and ovarian cancer. Hence, improving mechanistic understanding of HR has emerged as an urgent issue to address due to the high clinical demand. Ubiquitin modification plays a central role in HR and more than a few E3 ubiquitin ligases have been implicated in the process. However, the significance of the activity of one such key E3 ligase, BRCA1, has not yet been clarified and remains as a major obstacle in the field. Here, we review recent advances in our understanding of BRCA1 function in HR and discuss possible roles of the activity. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.