Abstract

Although instability in the number and structure of chromosomes is a hallmark of cancer cells, neither its genesis nor its role in carcinogenesis is understood. We have previously shown that the inactivation of BRCA2 (a suppressor of breast, ovarian, pancreatic and other cancers in humans) leads to spontaneous chromosome instability in dividing cells, providing a powerful model to explore the connections between chromosomal instability and cancer. I will discuss our recent studies concerning the functions of BRCA2 in the repair of chromosome breaks by homologous DNA recombination, and the completion of chromosome segregation during mitosis, in the context of a new murine model that recapitulates tissue-specific carcinogenesis in BRCA2 mutation carriers. The near-universal occurrence of chromosome instability in human cancers suggests avenues for its exploitation in cancer therapy; I will discuss early results with new approaches to this end.