| Autor: |
Fabian, Gut, Lisa, Käshammer, Katja, Lammens, Joseph D, Bartho, Anna-Maria, Boggusch, Erik, van de Logt, Brigitte, Kessler, Karl-Peter, Hopfner |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Molecular Cell. 82:3513-3522.e6 |
| ISSN: |
1097-2765 |
| DOI: |
10.1016/j.molcel.2022.07.019 |
| Popis: |
DNA double-strand breaks (DSBs) threaten genome stability and are linked to tumorigenesis in humans. Repair of DSBs requires the removal of attached proteins and hairpins through a poorly understood but physiologically critical endonuclease activity by the Mre11-Rad50 complex. Here, we report cryoelectron microscopy (cryo-EM) structures of the bacterial Mre11-Rad50 homolog SbcCD bound to a protein-blocked DNA end and a DNA hairpin. The structures reveal that Mre11-Rad50 bends internal DNA for endonucleolytic cleavage and show how internal DNA, DNA ends, and hairpins are processed through a similar ATP-regulated conformational state. Furthermore, Mre11-Rad50 is loaded onto blocked DNA ends with Mre11 pointing away from the block, explaining the distinct biochemistries of 3' → 5' exonucleolytic and endonucleolytic incision through the way Mre11-Rad50 interacts with diverse DNA ends. In summary, our results unify Mre11-Rad50's enigmatic nuclease diversity within a single structural framework and reveal how blocked DNA ends and hairpins are processed. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
