RPA is the major single-strand DNA binding protein required for DNA replication, DNA repair, and recombination. Phosphorylation and de-phosphorylation appear to be specifically required for its role in homologous recombination. We are investigating how phosphorylated RPA engages other proteins involved in homologous recombination. In addition, we are investigating how p53 regulates homologous recombination, through its interaction with RPA. A dissociation of function mutation of p53 has been discovered, which maintains normal checkpoint and cell death functions of p53, while failing to suppress homologous recombination. A knock-in mouse study is ongoing.