Inhibiting homologous recombination by targeting RAD51 protein

Homologous recombination (HR) is involved in repairing DNA double-strand breaks (DSB), the most harmful for the cell. Regulating HR is essential for maintaining genomic stability. In many forms of cancer, over-activation of HR increases tumor resistance to DNA-damaging treatments. RAD51, HR's core protein, is very often over-expressed in these cancers and plays a critical role in cancer cell development and survival. Targeting RAD51 directly to reduce its activity and its expression is therefore one strategy to sensitize and overcome resistance cancer cells to existing DNA-damaging therapies which remains the limiting factor for the success of targeted therapy. This review describes the structure and biological roles of RAD51, summarizes the different targeted sites of RAD51 and its inhibitory compounds discovered and described in the last decade.

Automated summary

Homologous recombination (HR) plays a crucial role in repairing DNA double-strand breaks and regulating HR is essential for maintaining genomic stability. Over-activation of HR in many forms of cancer leads to increased tumor resistance to DNA-damaging treatments. RAD51, the core protein of HR, is often over-expressed in cancers and targeting RAD51 directly can sensitize cancer cells to existing therapies.