ArticleThe EMBO journal2014
ATP-driven Rad50 conformations regulate DNA tethering, end resection, and ATM checkpoint signaling.
Article in The EMBO journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 102 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
102 citing papers in PubMed, 142 citations in OpenAlex.
- Basic-patch mutations in bacteriophage T4 Rad50 uncouple ATPase activation from processive nuclease activity.Bioscience reports · 2026Article
- A phosphorylation switch at MRE11 links ATM-ATR and calcium signaling to safeguard stalled replication fork stability.Research square · 2026Article
- Sae2 integrates CDK and checkpoint phosphorylation to coordinate MRX cleavage with checkpoint attenuation.Communications biology · 2025Article
- Insight into meiotic DNA end resection: Mechanisms and regulation.DNA repair · 2025Review
- Structure guided functional analysis of the S. cerevisiae Mre11 complex.Nature communications · 2025Article
- Dynamic conformations of the P. furiosus MR-DNA complex link Mre11 nuclease activity to DNA-stimulated Rad50 ATP hydrolysis.Communications biology · 2025Article
- Comprehensive structural and functional analyses of RAD50 nsSNPs: from prediction to impact assessment.Frontiers in bioinformatics · 2025Article
- Functional and molecular insights into the role of Sae2 C-terminus in the activation of MRX endonuclease.Nucleic acids research · 2024Article
- Binding of the TRF2 iDDR motif to RAD50 highlights a convergent evolutionary strategy to inactivate MRN at telomeres.Nucleic acids research · 2024Article
- Rif2 interaction with Rad50 counteracts Tel1 functions in checkpoint signalling and DNA tethering by releasing Tel1 from MRX binding.Nucleic acids research · 2024Article
- Dynamic Properties of the DNA Damage Response Mre11/Rad50 Complex.International journal of molecular sciences · 2023Review
- Three segment ligation of a 104 kDa multi-domain protein by SrtA and OaAEP1.Journal of biomolecular NMR · 2023Article
- An Extremely Stable Interprotein Tetrahedral Hg(Cys)Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- To Fix or Not to Fix: Maintenance of Chromosome Ends Versus Repair of DNA Double-Strand Breaks.Cells · 2022Review
- Mechanism, cellular functions and cancer roles of polymerase-theta-mediated DNA end joining.Nature reviews. Molecular cell biology · 2022Review
- Article
- The DNA damage checkpoint: A tale from budding yeast.Frontiers in genetics · 2022Review
- Universally Accessible Structural Data on Macromolecular Conformation, Assembly, and Dynamics by Small Angle X-Ray Scattering for DNA Repair Insights.Methods in molecular biology (Clifton, N.J.) · 2022Article
- DNA end resection during homologous recombination.Current opinion in genetics & development · 2021Review
- DNA End Joining: G0-ing to the Core.Biomolecules · 2021Review
42 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
The Mre11-Rad50 complex is highly conserved, yet the mechanisms by which Rad50 ATP-driven states regulate the sensing, processing and signaling of DNA double-strand breaks are largely unknown. Here we design structure-based mutations in Pyrococcus furiosus Rad50 to alter protein core plasticity and residues undergoing ATP-driven movements within the catalytic domains. With this strategy we identify Rad50 separation-of-function mutants that either promote or destabilize the ATP-bound state. Crystal structures, X-ray scattering, biochemical assays, and functional analyses of mutant PfRad50 complexes show that the ATP-induced 'closed' conformation promotes DNA end binding and end tethering, while hydrolysis-induced opening is essential for DNA resection. Reducing the stability of the ATP-bound state impairs DNA repair and Tel1 (ATM) checkpoint signaling in Schizosaccharomyces pombe, double-strand break resection in Saccharomyces cerevisiae, and ATM activation by human Mre11-Rad50-Nbs1 in vitro, supporting the generality of the P. furiosus Rad50 structure-based mutational analyses. These collective results suggest that ATP-dependent Rad50 conformations switch the Mre11-Rad50 complex between DNA tethering, ATM signaling, and 5' strand resection, revealing molecular mechanisms regulating responses to DNA double-strand breaks.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.