ArticleGenes & development2014
The Rad50 hook domain regulates DNA damage signaling and tumorigenesis.
Article in Genes & development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed.
- Crashing by design: Utilizing DNA damage for MCC differentiation.Trends in cell biology · 2026Article
- The DNA damage response pathway is required for multiciliated cell differentiation.Current biology : CB · 2026Article
- RAD50 missense variants differentially affect the DNA damage response and mitotic progression.FEBS letters · 2025Article
- Contribution of MRE11, RAD50, and NBS1 Genotypes to Bladder Cancer Susceptibility.Cancer genomics & proteomics · 2025Article
- Mouse MRE11-RAD50-NBS1 is needed to start and extend meiotic DNA end resection.Nature communications · 2025Article
- Binding of the TRF2 iDDR motif to RAD50 highlights a convergent evolutionary strategy to inactivate MRN at telomeres.Nucleic acids research · 2024Article
- Review
- Genes in loci genetically associated with polycystic ovary syndrome are dynamically expressed in human fetal gonadal, metabolic and brain tissues.Frontiers in endocrinology · 2023Article
- A rad50 germline mutation induces tumorigenesis and ataxia-telangiectasia phenotype in a transparent medaka model.PloS one · 2023Article
- Colocalization analysis of polycystic ovary syndrome to identify potential disease-mediating genes and proteins.European journal of human genetics : EJHG · 2021Article
- Meiotic Recombination Defects and Premature Ovarian Insufficiency.Frontiers in cell and developmental biology · 2021Review
- NBS1 is required for SPO11-linked DNA double-strand break repair in male meiosis.Cell death and differentiation · 2020Article
- 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
- Challenges and Perspectives in Homology-Directed Gene Targeting in Monocot Plants.Rice (New York, N.Y.) · 2019Review
- MRE11-RAD50-NBS1 complex alterations and DNA damage response: implications for cancer treatment.Molecular cancer · 2019Review
- DDX5 plays essential transcriptional and post-transcriptional roles in the maintenance and function of spermatogonia.Nature communications · 2019Article
- Histone demethylase UTX is a therapeutic target for diabetic kidney disease.The Journal of physiology · 2019Article
- Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
The Mre11 complex (Mre11, Rad50, and Nbs1) is a central component of the DNA damage response (DDR), governing both double-strand break repair and DDR signaling. Rad50 contains a highly conserved Zn(2+)-dependent homodimerization interface, the Rad50 hook domain. Mutations that inactivate the hook domain produce a null phenotype. In this study, we analyzed mutants with reduced hook domain function in an effort to stratify hook-dependent Mre11 complex functions. One of these alleles, Rad50(46), conferred reduced Zn(2+) affinity and dimerization efficiency. Homozygous Rad50(46/46) mutations were lethal in mice. However, in the presence of wild-type Rad50, Rad50(46) exerted a dominant gain-of-function phenotype associated with chronic DDR signaling. At the organismal level, Rad50(+/46) exhibited hydrocephalus, liver tumorigenesis, and defects in primitive hematopoietic and gametogenic cells. These outcomes were dependent on ATM, as all phenotypes were mitigated in Rad50(+/46) Atm(+/-) mice. These data reveal that the murine Rad50 hook domain strongly influences Mre11 complex-dependent DDR signaling, tissue homeostasis, and tumorigenesis.
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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.