Dynamic conformations of the P. furiosus MR-DNA complex link Mre11 nuclease activity to DNA-stimulated Rad50 ATP hydrolysis.

ABSTRACT: The MRE11-RAD50-NBS1/Xrs2 (MRN/X) protein complex has essential roles in the repair of damaged DNA. The current understanding of the conformational landscape of the core MR complex comes from various structural studies. However, given the heterogeneous nature of these structures, we suspect that several conformational states may still be unaccounted for. Here, we use methyl-based NMR experiments on P. furiosus MR to determine an ensemble of distinct conformations of MR bound to DNA, consistent with the highly dynamic nature of the MR-DNA complex. Interrogation of these structures via in vitro activity assays on MR mutants reveal an unexpected, striking correlation between the nuclease activity of Mre11 and the magnitude of DNA-stimulated ATP hydrolysis by Rad50. Together, the structures an

SUBMITTER: Canny MD 

PROVIDER: S-EPMC11965522 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature