DNA double-strand breaks (DSBs) are most lethal chromosomal lesions that lead to replication fork collapsed and genome instability. Homologous recombination (HR) is a major error-free repair pathway to eliminate these pre-carcinogenic chromosomal DSBs. As such, dysregulation of HR drives the tumorigenesis and cancer evolution. The well-known example is the American actress, Angelina Jolie, who chose prophylactic surgery for cancer prevention after gene sequencing detected a mutation to a recombination repair gene like BRCA1. Interestingly, cancer cells harboring genetic mutations in recombination repair genes, namely BRCAness, will sensitize to PARP inhibitors such as olaparib. Thus, understanding the action mechanism of recombination-mediated DSB repair will provide great application value in cancer prevention and precision medicine for the treatment of various cancers that arise because of recombination repair deficiency. Here, I will present our recent work regarding the mechanism of recombination repair and its possible applications.