Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage

Abstract

BRCA1 (BReast-CAncer susceptibility gene 1) and BRCA2 are tumor suppressor genes, the mutant phenotypes of which predispose to breast and ovarian cancers. Intensive research has shown that BRCA proteins are involved in a multitude of pivotal cellular processes. In particular, both genes contribute to DNA repair and transcriptional regulation in response to DNA damage. Recent studies suggest that BRCA proteins are required for maintenance of chromosomal stability, thereby protecting the genome from damage. New data also show that BRCAs transcriptionally regulate some genes involved in DNA repair, the cell cycle, and apoptosis. Many of these functions are mediated by a large number of cellular proteins that interact with BRCAs. The functions of BRCA proteins are also linked to distinct and specific phosphorylation events; however, the extent to which phosphorylation-activated molecular pathways contribute to tumor suppressor activity remains unclear. Finally, the reasons why mutations in BRCA genes lead to the development of breast and ovarian cancers are not clearly understood. Elucidation of the precise molecular functions of BRCAs is expected to improve our understanding of hereditary as well as sporadic mammary carcinogenesis.