The Mre11-Rad50 nuclease complex has important functions to initiate the repair of broken DNA. A collaborative study of the Cejka (IRB Bellinzona) and Peter laboratories (ETH Zurich) took a new approach to image the DNA repair proteins in action.
The researchers used a technique termed transmission electron microscopy, which allowed to visualize broken DNA, and the repair proteins, including Mre11-Rad50 and Sae2, that act on the DNA molecules. The key observation of the study was that the proteins form large assemblies that include multiple subunits. It is thought that these proteins load on DNA bound together. This allows them to initiate the repair process by acting on the broken DNA at many sites at the same time.
Although the study employed proteins from the yeast model organism S. cerevisiae, the proteins are though to function very similarly also in human cells. In fact, the region of the Rad50 protein that was found to be required for the multiprotein assembly is often mutated in human cancers, suggesting that the formation of the protein complex is a necessary for proper DNA repair and cancer avoidance.
Vera Kissling, jointly supervised by the Cejka and Peter laboratories, performed most of the experiments described in the publication, together with Giordano Reginato (IRB Bellinzona) and Eliana Bianco (ETH Zurich). The research was funded by a grant from the Helmut Horten Foundation.
Kissling, V. M., G. Reginato, E. Bianco, K. Kasaciunaite, J. Tilma, G. Cereghetti, N. Schindler, S. S. Lee, R. Guerois, B. Luke, R. Seidel, P. Cejka and M. Peter
Nat Commun. 2022; 13:2374.
Transmission electron microscopy of Mre11-Rad50 binding to plasmid DNA at 30 °C with co-factors.
MR dimers oligomerizing on DNA and some MR molecules forming “pearls-on-a-string”-like structures (zoom-insets of examples with cartoons),
irrespective of DNA ends.