Structure-function relationships of the Mre11 protein in the control of DNA end bridging and processing.

The evolutionarily conserved Mre11-Rad50-Xrs2 (MRX) complex cooperates with the Sae2 protein in initiating resection of DNA double-strand breaks (DSBs) and in maintaining the DSB ends tethered to each other for their accurate repair. How these MRX-Sae2 functions contribute to DNA damage resistance is not understood. By taking advantage of mre11 alleles that suppress the hypersensitivity of sae2∆ cells to genotoxic agents, we have recently found that Mre11 can be divided in two structurally distinct domains that support resistance to genotoxic agents by mediating different processes. While the Mre11 N-terminal domain impacts on the resection activity of long-range resection nucleases by mediating MRX and Tel1/ATM association to DNA DSBs, the C-terminus influences the MRX-tethering activity by its virtue to interact with Rad50. Given the evolutionary conservation of the MRX complex, our results have implications for understanding the consequences of its dysfunctions in human diseases.