Our research focusses on the molecular mechanisms of DNA double-strand break repair and the treatment of breast cancer. The biologically significant DNA damage caused by ionizing radiation and a number of cytotoxic drugs requires double-strand break repair for survival. The major research focus is the DNA repair pathway of homologous recombination, which is often dysregulated in human tumor cells by a variety of mechanisms. Homologous recombination involves many nuclear proteins, including the breast cancer genes, BRCA1 and BRCA2, whose function is inactivated in familial breast or ovarian cancers. Subsets of human breast cancers may be particularly susceptible to treatment strategies designed to exploit a deficiency in homologous recombination. Most DNA repair pathways involve sensing and signaling as well as direct repair proteins, and the upstream signaling to activate homologous recombination may be determined by both double-strand break processing as well as chromatin remodeling. Furthermore, the primary function of homologous recombination may be to restart stalled replication forks, blocked by particular types of DNA damage. The laboratory focus is to understand the roles of the proteins involved in homologous recombination, with particular attention to the different types of DNA damage that a cell may encounter. In addition, why BRCA1 and BRCA2 deficiencies predispose to breast and ovarian cancer rather than other tumor types is under investigation.
