On the Way to Breast Cancer

Abstract

MOLECULAR MEDICINE The BRCA2 gene is mutated in a subset of families with an inherited susceptibility to breast and ovarian cancer. Intense efforts to understand how the BRCA2 protein prevents cancer development have focused attention on three critical processes in the cell nucleus: DNA repair, transcription, and chromatin remodeling. New support for the idea that BRCA2 participates in one or more of these processes is provided by Hughes-Davies et al. , who identify a nuclear protein (EMSY) that binds to a region of BRCA2 that is deleted in cancer. EMSY represses the trans-activation domain of BRCA2, is localized to sites of DNA damage, and binds to proteins with sequence motifs characteristic of chromatin regulators. The EMSY gene is amplified in sporadic breast and ovarian cancers, which typically do not have mutations in BRCA2. Thus, EMSY amplification and BRCA2 deletion may have similar effects on signaling pathway(s) critical to the pathogenesis of the rare inherited forms of these cancers as well as more common cancers. — PAK Cell 115 , 523 (2003).