Figure 1.

Mdm2/Mdmx inhibit MRN-mediated DNA break repair and p53-mediated transcription. DNA damage activates the MRN complex to induce DNA break repair and p53-mediated transcription that facilitates DNA repair through multiple mechanisms. Both the MRN complex and p53 are inhibited by Mdm2/Mdmx. Failure to repair DNA breaks can result in genome instability and apoptosis. Compounds that inhibit Mdm2/Mdmx:p53 interactions and/or increase Mdm2 levels, resulting in increased inhibition of the MRN complex, impact DNA break repair and genome instability. These compounds combined with DNA damaging agents can lead to increased cancer cell apoptosis.