ATP-dependent DNA binding, unwinding, and resection by the Mre11/Rad50 complex

ATP-dependent DNA end recognition and nucleolytic processing are central functions of the Mre11/Rad50 (MR) complex in DNA double-strand break repair. However, it is still unclear how ATP binding and hydrolysis primes the MR function and regulates repair pathway choice in cells. Here, Methanococcus jannaschii MR-ATPS-DNA structure reveals that the partly deformed DNA runs symmetrically across central groove between two ATPS-bound Rad50 nucleotide-binding domains. Duplex DNA cannot access the Mre11 active site in the ATP-free full-length MR complex. ATP hydrolysis drives rotation of the nucleotide-binding domain and induces the DNA melting so that the substrate DNA can access Mre11. Our findings suggest that the ATP hydrolysis-driven conformational changes in both DNA and the MR complex coordinate the melting and endonuclease activity.

Source: EMBO Journal - March 30, 2016 Category: Molecular Biology Authors: Liu, Y., Sung, S., Kim, Y., Li, F., Gwon, G., Jo, A., Kim, A.-K., Kim, T., Song, O.-k., Lee, S. E., Cho, Y. Tags: DNA Replication, Repair & Recombination, Structural Biology Articles Source Type: research