Mesoscale conformational changes in the DNA-repair complex Rad50/Mre11/Nbs1 upon binding DNA
Copyright policy )Mesoscale conformational changes in the DNA-repair complex Rad50/Mre11/Nbs1 upon binding DNA
The human Rad50/Mre11/Nbs1 complex (hR/M/N) functions as an essential guardian of genome integrity by directing the proper processing of DNA ends, including DNA breaks. This biological function results from its ability to tether broken DNA molecules. hR/M/N's dynamic molecular architecture consists of a globular DNA-binding domain from which two 50-nm-long coiled coils protrude. The coiled coils are flexible and their apices can self-associate. The flexibility of the coiled coils allows their apices to adopt an orientation favourable for interaction. However, this also allows interaction between the tips of two coiled coils within the same complex, which competes with and frustrates the intercomplex interaction required for DNA tethering. Here we show that the dynamic architecture of hR/M/N is markedly affected by DNA binding. DNA binding by the hR/M/N globular domain leads to parallel orientation of the coiled coils; this prevents intracomplex interactions and favours intercomplex associations needed for DNA tethering. The hR/M/N complex thus is an example of a biological nanomachine in which binding to its ligand, in this case DNA, affects the functional conformation of a domain located 50 nm distant.
- Delft University of Technology Netherlands
- Erasmus University Rotterdam Netherlands
MRE11 Homologue Protein, DNA Repair, Protein Conformation, Adenylyl Imidodiphosphate, Nuclear Proteins, Cell Cycle Proteins, DNA, Buffers, Ligands, Microscopy, Atomic Force, Acid Anhydride Hydrolases, EMC MM-03-32-04, DNA-Binding Proteins, DNA Repair Enzymes, Multiprotein Complexes, Humans, Nucleic Acid Conformation, EMC MGC-01-12-03, Pliability, Protein Binding
MRE11 Homologue Protein, DNA Repair, Protein Conformation, Adenylyl Imidodiphosphate, Nuclear Proteins, Cell Cycle Proteins, DNA, Buffers, Ligands, Microscopy, Atomic Force, Acid Anhydride Hydrolases, EMC MM-03-32-04, DNA-Binding Proteins, DNA Repair Enzymes, Multiprotein Complexes, Humans, Nucleic Acid Conformation, EMC MGC-01-12-03, Pliability, Protein Binding
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).236 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!