ArticleNucleic acids research2019
The ATP-bound conformation of the Mre11-Rad50 complex is essential for Tel1/ATM activation.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- Article
- DNA Damage and Replication Stress Checkpoints.Annual review of biochemistry · 2025Review
- Dynamic conformations of the P. furiosus MR-DNA complex link Mre11 nuclease activity to DNA-stimulated Rad50 ATP hydrolysis.Communications biology · 2025Article
- Article
- Comprehensive structural and functional analyses of RAD50 nsSNPs: from prediction to impact assessment.Frontiers in bioinformatics · 2025Article
- 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
- Double heterozygous mutation in RAD50 and ATM genes in a Peruvian family with five cancer types: a case report.Revista de la Facultad de Ciencias Medicas (Cordoba, Argentina) · 2022Article
- Article
- The DNA damage checkpoint: A tale from budding yeast.Frontiers in genetics · 2022Review
- Mapping yeast mitotic 5' resection at base resolution reveals the sequence and positional dependence of nucleases in vivo.Nucleic acids research · 2021Article
- Rad50 promotes ovarian cancer progression through NF-κB activation.Journal of cellular and molecular medicine · 2021Article
- Novel insights into the mechanism of cell cycle kinases Mec1(ATR) and Tel1(ATM).Critical reviews in biochemistry and molecular biology · 2021Article
- The dynamic nature of the Mre11-Rad50 DNA break repair complex.Progress in biophysics and molecular biology · 2021Review
- Review
- Inhibition of MRN activity by a telomere protein motif.Nature communications · 2021Article
- Mechanism of MRX inhibition by Rif2 at telomeres.Nature communications · 2021Article
- Biochemical and structural characterization of analogs of MRE11 breast cancer-associated mutant F237C.Scientific reports · 2021Article
- The MRN complex promotes DNA repair by homologous recombination and restrains antigenic variation in African trypanosomes.Nucleic acids research · 2021Article
- Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the checkpoint protein Tel1 requires the Mre11-Rad50-Xrs2 (MRX) complex, which recruits Tel1 at DNA double-strand breaks (DSBs) through direct interaction between Tel1 and Xrs2. However, in vitro Tel1 activation by MRX requires ATP binding to Rad50, suggesting a role also for the MR subcomplex in Tel1 activation. Here we describe two separation-of-functions alleles, mre11-S499P and rad50-A78T, which we show to specifically affect Tel1 activation without impairing MRX functions in DSB repair. Both Mre11-S499P and Rad50-A78T reduce Tel1-MRX interaction leading to poor Tel1 association at DSBs and consequent loss of Tel1 activation. The Mre11-S499P variant reduces Mre11-Rad50 interaction, suggesting an important role for MR complex formation in Tel1 activation. Molecular dynamics simulations show that the wild type MR subcomplex bound to ATP lingers in a tightly 'closed' conformation, while ADP presence leads to the destabilization of Rad50 dimer and of Mre11-Rad50 association, both events being required for MR conformational transition to an open state. By contrast, MRA78T undertakes complex opening even if Rad50 is bound to ATP, indicating that defective Tel1 activation caused by MRA78T results from destabilization of the ATP-bound conformational state.
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