Homologous recombination is a highly conserved determinant of the synergistic cytotoxicity between cisplatin and DNA topoisomerase I poisons.

Phase I and II clinical trails are currently investigating the antitumor activity of cisplatin and camptothecins (CPTs; DNA topoisomerase I poisons), based on the dramatic synergistic cytotoxicity of these agents in some preclinical models. However, the mechanistic basis for this synergism is poorly understood. By exploiting the evolutionary conservation of DNA repair pathways from genetically tractable organisms such as budding and fission yeasts to mammalian cells, we demonstrate that the synergism of CPT and cisplatin requires homologous recombination.