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Mechanism of DNA End Sensing and Processing by the Mre11-Rad50 Complex.
- Source :
-
Molecular Cell . Nov2019, Vol. 76 Issue 3, p382-382. 1p. - Publication Year :
- 2019
-
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. • cryo-EM structure of Ec Mre11-Rad50 bound to a DNA break • Mre11 dimer binds the DNA end at the side of Rad50 • Mre11 and Rad50 assemble a transient DNA cutting channel • The coiled coils form a rod-shaped DNA gate and clamp Käshammer et al. use cryoelectron microscopy and biochemical studies to reveal, at near-atomic resolution, how the ATP-dependent nuclease Mre11-Rad50 can sense and process a wide range of DNA termini to enable repair and recombination of breaks and hairpins in chromosomal DNA. [ABSTRACT FROM AUTHOR]
- Subjects :
- *DOUBLE-strand DNA breaks
*DNA
Subjects
Details
- Language :
- English
- ISSN :
- 10972765
- Volume :
- 76
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Molecular Cell
- Publication Type :
- Academic Journal
- Accession number :
- 139504656
- Full Text :
- https://doi.org/10.1016/j.molcel.2019.07.035