6s85
From Proteopedia
Cutting state of the E. coli Mre11-Rad50 (SbcCD) head complex bound to ADP and dsDNA.
Structural highlights
FunctionSBCC_ECOLI SbcCD cleaves DNA hairpin structures. These structures can inhibit DNA replication and are intermediates in certain DNA recombination reactions. The complex acts as a 3'->5' double strand exonuclease that can open hairpins. It also has a 5' single-strand endonuclease activity. Publication Abstract from PubMedDNA 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. Mechanism of DNA End Sensing and Processing by the Mre11-Rad50 Complex.,Kashammer L, Saathoff JH, Lammens K, Gut F, Bartho J, Alt A, Kessler B, Hopfner KP Mol Cell. 2019 Nov 7;76(3):382-394.e6. doi: 10.1016/j.molcel.2019.07.035. Epub, 2019 Sep 3. PMID:31492634[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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