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-Structure paper
Title | Mechanism of DNA End Sensing and Processing by the Mre11-Rad50 Complex. |
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Journal, issue, pages | Mol Cell, Vol. 76, Issue 3, Page 382-394.e6, Year 2019 |
Publish date | Nov 7, 2019 |
Authors | Lisa Käshammer / Jan-Hinnerk Saathoff / Katja Lammens / Fabian Gut / Joseph Bartho / Aaron Alt / Brigitte Kessler / Karl-Peter Hopfner / |
PubMed Abstract | 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- ...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. |
External links | Mol Cell / PubMed:31492634 |
Methods | EM (single particle) |
Resolution | 3.5 - 15.6 Å |
Structure data | EMDB-10107, PDB-6s6v: EMDB-10114: EMDB-10115: EMDB-10116, PDB-6s85: |
Chemicals | ChemComp-MN: ChemComp-AGS: ChemComp-MG: ChemComp-ADP: |
Source |
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Keywords | DNA BINDING PROTEIN / Nuclease / DNA repair / ABC-type ATPase / DNA double-strand breaks |