Cryo-EM structure of the Mre11-Rad50-Nbs1 complex reveals the molecular mechanism of scaffolding functions
Molecular Cell article – more structural insights from collaborative project including Katja Lammens
19.01.2023
Matthias Rotheneder, Kristina Stakyte, Erik van de Logt, Joseph D. Bartho, Katja Lammens, Yilan Fan, Aaron Alt, Brigitte Kessler, Christophe Jung, Wynand P. Roos, Barbara Steigenberger, and Karl-Peter Hopfner (2023 Jan 19) Cryo-EM structure of the Mre11-Rad50-Nbs1 complex reveals the molecular mechanism of scaffolding functions, Molecular Cell Volume 83, ISSUE 2, P167-185.e9. https://doi.org/10.1016/j.molcel.2022.12.003 (Project B02)
Summary cited from the article:
The DNA double-strand break repair complex Mre11-Rad50-Nbs1 (MRN) detects and nucleolytically processes DNA ends, activates the ATM kinase, and tethers DNA at break sites. How MRN can act both as nuclease and scaffold protein is not well understood. The cryo-EM structure of MRN from Chaetomium thermophilum reveals a 2:2:1 complex with a single Nbs1 wrapping around the autoinhibited Mre11 nuclease dimer. MRN has two DNA-binding modes, one ATP-dependent mode for loading onto DNA ends and one ATP-independent mode through Mre11’s C terminus, suggesting how it may interact with DSBs and intact DNA. MRNs two 60-nm-long coiled-coil domains form a linear rod structure, the apex of which is assembled by the two joined zinc-hook motifs. Apices from two MRN complexes can further dimerize, forming 120-nm spanning MRN-MRN structures. Our results illustrate the architecture of MRN and suggest how it mechanistically integrates catalytic and tethering functions.
