Links between genome integrity and BRCA1 tumor suppression

BRCA1 and BRCA2 are two major breast and ovarian cancer susceptibility genes. BRCA1 was the first discovered and has been a focus of research for these cancers. BRCA1 mediates tumor suppression in part through pleiotropic interactions with a network of DNA repair proteins on chromatin. BRCA1 mutations cause homologous recombination (HR)-mediated DNA repair deficiency, genomic instability, and DNA-damaging agent hypersensitivity. Although BRCA1 and BRCA2 have some shared functions in cancer predisposition and therapy response, there are also key differences indicating divergent roles for each protein. This review summarizes and highlights recent insights into the molecular events responsible for BRCA1 tumor suppression, emphasizing the DNA repair function of BRCA1 as a nexus between its roles in cancer development and therapy.