Mechanism of DNA End Sensing and Processing by the Mre11-Rad50 Complex
| Autor: | Joseph Bartho, Karl-Peter Hopfner, Jan-Hinnerk Saathoff, Brigitte Kessler, Aaron Alt, Fabian Gut, Katja Lammens, Lisa Käshammer |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
DNA Replication
DNA Bacterial Exonucleases DNA repair Biology DNA-binding protein Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Escherichia coli DNA Breaks Double-Stranded A-DNA Molecular Biology 030304 developmental biology Coiled coil MRE11 Homologue Protein 0303 health sciences Nuclease Deoxyribonucleases Escherichia coli Proteins Cryoelectron Microscopy Cell Biology Acid Anhydride Hydrolases Cell biology enzymes and coenzymes (carbohydrates) chemistry Rad50 biology.protein Nucleic Acid Conformation biological phenomena cell phenomena and immunity Homologous recombination 030217 neurology & neurosurgery DNA |
| Zdroj: | Molecular Cell. 76:382-394.e6 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2019.07.035 |
| Popis: | Summary DNA double-strand breaks (DSBs) threaten genome stability throughout life and are linked to tumorigenesis in humans. To initiate DSB repair by end joining or homologous recombination, the Mre11-nuclease Rad50-ATPase complex detects and processes diverse and obstructed DNA ends, but a structural mechanism is still lacking. Here we report cryo-EM structures of the E. coli Mre11-Rad50 homolog SbcCD in resting and DNA-bound cutting states. In the resting state, Mre11’s nuclease is blocked by ATP-Rad50, and the Rad50 coiled coils appear flexible. Upon DNA binding, the two coiled coils zip up into a rod and, together with the Rad50 nucleotide-binding domains, form a clamp around dsDNA. Mre11 moves to the side of Rad50, binds the DNA end, and assembles a DNA cutting channel for the nuclease reactions. The structures reveal how Mre11-Rad50 can detect and process diverse DNA ends and uncover a clamping and gating function for the coiled coils. |
| Databáze: | OpenAIRE |
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