Mechanism of DNA End Sensing and Processing by the Mre11-Rad50 Complex.
Acid Anhydride Hydrolases
/ genetics
Cryoelectron Microscopy
DNA Breaks, Double-Stranded
DNA Replication
DNA, Bacterial
/ genetics
Deoxyribonucleases
/ genetics
Escherichia coli
/ enzymology
Escherichia coli Proteins
/ genetics
Exonucleases
/ genetics
MRE11 Homologue Protein
/ genetics
Nucleic Acid Conformation
Structure-Activity Relationship
ABC ATPase
DNA double-strand breaks
DNA repair
Mre11-Rad50 complex
SMC-like proteins
SbcC-SbcD complex
coiled-coil
cryoelectron microscopy
homologous recombination
nuclease
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
07 11 2019
07 11 2019
Historique:
received:
22
03
2019
revised:
17
06
2019
accepted:
25
07
2019
pubmed:
8
9
2019
medline:
26
2
2020
entrez:
8
9
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31492634
pii: S1097-2765(19)30590-8
doi: 10.1016/j.molcel.2019.07.035
pii:
doi:
Substances chimiques
DNA, Bacterial
0
Escherichia coli Proteins
0
SbcC protein, E coli
0
Deoxyribonucleases
EC 3.1.-
Exonucleases
EC 3.1.-
MRE11 Homologue Protein
EC 3.1.-
sbcD protein, E coli
EC 3.1.-
Acid Anhydride Hydrolases
EC 3.6.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Video-Audio Media
Langues
eng
Sous-ensembles de citation
IM
Pagination
382-394.e6Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.