Eukaryotic Rad50 Functions as A Rod-shaped Dimer

The Rad50 hook interface is crucial for assembly and functions of the Mre11 complex. Previous analyses suggest that Rad50 molecules interact within (intra-complex) or between (inter-complex) dimeric complexes. In this study, we determined the structure of the human Rad50 hook and coiled-coil domain. The data suggest that the predominant structure is the intra-complex, in which the two parallel coiled-coils proximal to the hook form a rod-shape, and that a novel interface within the coiled-coil domains of Rad50 stabilizes the interaction of Rad50 protomers within the dimeric assembly. In yeast, removal of the coiled-coil interface compromised Tel1 activation without affecting DNA repair, while simultaneous disruption of that interface and the hook phenocopied a null mutation. The results demonstrate that the hook and coiled-coil interfaces coordinately promote intra-complex assembly and define it as the functional form of the Mre11 complex.