RAD51 recombinase: biology, regulation, and therapeutic targeting

Abstract

Accurate repair of DNA double-strand breaks (DSBs) is essential for maintaining genomic integrity. RAD51, the core recombinase in homologous recombination, plays central roles in repairing DNA damage and protecting stalled replication forks. In normal cells, RAD51 helps maintain genomic integrity; however, in cancer, its overexpression often supports replication-stress tolerance, as well as resistance to chemotherapy, radiotherapy, and PARP inhibitors. RAD51 is tightly controlled at multiple levels, including transcriptional, post-transcriptional, and post-translational regulation, which together shape its activity in different biological contexts. This review summarizes the structural features of RAD51, its regulatory networks, and its roles in human disease, with particular emphasis on cancer progression and treatment resistance. Currently available RAD51 inhibitors, their mechanisms of action, and the main challenges that still limit clinical translation are discussed. Together, current findings indicate that RAD51 is a key genome maintenance factor and a promising therapeutic target in precision oncology.

Keywords

RAD51 / Homologous recombination / DNA repair / RAD51 inhibitors / Synthetic lethality

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