The invention relates to a novel double hybrid system and to the uses thereof. This system provides, in particular, a tool that enables the detection of the interruption of a protein-protein interaction. The developed system uses transcription interference as a mechanism for detecting a breaking up of interacting protein pairs. The developed double hybrid system can be applied to the screening of molecules enabling the detection of molecules breaking up a protein-protein interaction as well as enabling the identification of alleles lacking in the interaction of proteins involved in the protein-protein interactions.