Break-induced replication (BIR) is an important DNA repair pathway proposed to recover collapsed replication forks at DNA fragile sites. My research revealed that BIR has trouble traversing DNA fragile sites, and often results in chromosomal rearrangement and exacerbated mutagenesis, which can contribute to cancer development. Through a whole genome screen, I also identified 160 genes that represent BIR regulators (e.g. cell trafficking and stress response pathway genes) that were never before characterized as such.