One goal in the laboratory is to identify new proteins and pathways that promote genome integrity. To accomplish this aim, we have initiated several large-scale, high-throughput genetic screens using libraries of RNAi molecules. Two screens have been completed identifying approximately 250 candidate DNA damage-response proteins. Efforts are underway to validate these candidates, sort them into functional categories, and define their genome maintenance activities. One of the genes we identified is SMARCAL1/HARP. SMARCAL1 functions at replication forks to maintain genome integrity. Finally, many of the genes we identified have been linked to cancer. Therefore, we are investigating whether disruption of their activities promotes tumorigenesis.