ArticleThe Journal of biological chemistry2012
Rad50 zinc hook is important for the Mre11 complex to bind chromosomal DNA double-stranded breaks and initiate various DNA damage responses.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- The bacteriophage T4 homologous recombination system: mechanism, applications, conservation, and environmental significance.EcoSal Plus · 2025Review
- Novel impact of metal ion-induced cell death on diabetic cardiomyopathy pathogenesis and therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- ATM priming and end resection-coupled phosphorylation of MRE11 is important for fork protection and replication restart.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- 53BP1 deficiency leads to hyperrecombination using break-induced replication (BIR).Nature communications · 2024Article
- 53BP1 deficiency leads to hyperrecombination using break-induced replication (BIR).bioRxiv : the preprint server for biology · 2024Article
- Effects of RAD50 SNP, sodium intake, and H. pylori infection on gastric cancer survival in Korea.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Review
- Diabetic cardiomyopathy - Zinc preventive and therapeutic potentials by its anti-oxidative stress and sensitizing insulin signaling pathways.Toxicology and applied pharmacology · 2023Review
- A rad50 germline mutation induces tumorigenesis and ataxia-telangiectasia phenotype in a transparent medaka model.PloS one · 2023Article
- Rad50 zinc hook functions as a constitutive dimerization module interchangeable with SMC hinge.Nature communications · 2020Article
- Article
- Functional and structural insights into the MRX/MRN complex, a key player in recognition and repair of DNA double-strand breaks.Computational and structural biotechnology journal · 2020Review
- Sublethal treatment with plasma-activated medium induces senescence-like growth arrest of A549 cells: involvement of intracellular mobile zinc.Journal of clinical biochemistry and nutrition · 2019Article
- The Role of Nucleic Acid Sensing in Controlling Microbial and Autoimmune Disorders.International review of cell and molecular biology · 2019Review
- Processing of DNA Double-Strand Breaks by the MRX Complex in a Chromatin Context.Frontiers in molecular biosciences · 2019Review
- The MRE11-RAD50-NBS1 Complex Conducts the Orchestration of Damage Signaling and Outcomes to Stress in DNA Replication and Repair.Annual review of biochemistry · 2018Review
- Functional Analysis of the Bacteriophage T4 Rad50 Homolog (gp46) Coiled-coil Domain.The Journal of biological chemistry · 2015Article
- Envisioning the dynamics and flexibility of Mre11-Rad50-Nbs1 complex to decipher its roles in DNA replication and repair.Progress in biophysics and molecular biology · 2015Review
- The actin depolymerizing factor (ADF)/cofilin signaling pathway and DNA damage responses in cancer.International journal of molecular sciences · 2015Review
- Gingival fibroblasts resist apoptosis in response to oxidative stress in a model of periodontal diseases.Cell death discovery · 2015Article
- The Mre11/Rad50/Nbs1 complex: recent insights into catalytic activities and ATP-driven conformational changes.Experimental cell research · 2014Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The Mre11-Rad50-Nbs1 (MRN) complex plays critical roles in checkpoint activation and double-stranded break (DSB) repair. The Rad50 zinc hook domain mediates zinc-dependent intercomplex associations of MRN, which is important for DNA tethering. Studies in yeast suggest that the Rad50 zinc hook domain is essential for MRN functions, but its role in mammalian cells is not clear. We demonstrated that the human Rad50 hook mutants are severely defective in various DNA damage responses including ATM (Ataxia telangiectasia mutated) activation, homologous recombination, sensitivity to IR, and activation of the ATR pathway. By using live cell imaging, we observed that the Rad50 hook mutants fail to be recruited to chromosomal DSBs, suggesting a novel mechanism underlying the severe defects observed for the Rad50 hook mutants. In vitro analysis showed that Zn(2+) promotes wild type but not the hook mutant of MR to bind double-stranded DNA. In vivo, the Rad50 hook mutants are defective in being recruited to chromosomal DSBs in both H2AX-proficient and -deficient cells, suggesting that the Rad50 hook mutants are impaired in direct binding to chromosomal DSB ends. We propose that the Rad50 zinc hook domain is important for the initial binding of MRN to DSBs, leading to ATM activation to phosphorylate H2AX, which recruits more MRN to the DSB-flanking chromosomal regions. Our studies reveal a critical role for the Rad50 zinc hook domain in establishing and maintaining MRN recruitment to chromosomal DSBs and suggest an important mechanism of how the Rad50 zinc hook domain contributes to DNA repair and checkpoint activation.
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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.