EMD-10107
Resting state of the E. coli Mre11-Rad50 (SbcCD) head complex bound to ATPgS
EMD-10107
Single-particle3.5 Å
Deposition: 03/07/2019Map released: 04/09/2019
Last modified: 20/11/2019
Sample Organism:
Escherichia coli
Sample: Heterotetrameric complex of full-length Mre11-Rad50 in complex with ATPgS
Fitted models: 6s6v (Avg. Q-score: 0.486)
Deposition Authors: Kaeshammer L, Saathoff JH, Gut F, Bartho J, Alt A, Kessler B, Lammens K, Hopfner KP
Sample: Heterotetrameric complex of full-length Mre11-Rad50 in complex with ATPgS
Fitted models: 6s6v (Avg. Q-score: 0.486)
Deposition Authors: Kaeshammer L, Saathoff JH, Gut F, Bartho J, Alt A, Kessler B, Lammens K, Hopfner KP
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
(2019) Mol. Cell , 76 , 382
,
Alt A ,
Kessler B,
Hopfner KP
(2019) Mol. Cell , 76 , 382
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-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.
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.