The role of BRCA1 in DNA double-strand repair: Past and present

The breast cancer type 1 susceptibility protein (BRCA1) is involved in several important cellular pathways, including DNA damage repair, chromatin remodeling and checkpoint activation. The BRCA1 tumor suppression function has been attributed to its role in homologous recombination damage repair. In this review, historical facts concerning BRCA1, together with recent research advances regarding our understanding of the BRCA1 interacting proteins that are involved in, homologous recombination (HR) double strand break (DBS) repair and how these interacting proteins maintain chromosomal integrity, are discussed. In addition, this review poses the questions as to what extent HR repair cannot be properly fulfilled when breast cancer related mutations in the BRCA1 gene occur and how the recent and excessive studied poly-ADP ribose polymerase (PARP) inhibiting therapy approach links with the proposed tumor suppression function of the different BRCA1 domains.

► BRCA1 and its interacting proteins protect genome integrity.
► BRCA1 tumor suppression may be related to its homologous recombination function.
► The success of PARP inhibitors is not solely dependent on BRCA1 mutation itself.