Breast cancer and genetic instability: the molecules behind the scenes

Germline mutations in either the BRCA1 or the BRCA2 gene are responsible for the majority of hereditary breast cancers. The proposition that BRCA1 might play a role as a caretaker of the genome was first put forward by the demonstration that, in mitotic and meiotic cells, BRCA1 can interact with Rad51, which plays a major role in repair and/or recombination processes. From there, a fair body of observations have converged to support the concept that BRCA1 and BRCA2 play a role in monitoring and/or repairing DNA lesions. The relaxation of this monitoring caused by mutations of either of these two genes leaves unrepaired events, leading to the accumulation of mutations and ultimately to cancer. Understanding the precise biochemical function of BRCA1 and BRCA2 should provide a basis for early diagnosis and prevention in women carrying a predisposition to breast cancer.