ArticleGenes & development2005
The Rad50S allele promotes ATM-dependent DNA damage responses and suppresses ATM deficiency: implications for the Mre11 complex as a DNA damage sensor.
Article in Genes & development, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 89 citations in OpenAlex.
- Mutual, spatially limited control of meiotic DNA break formation by Mre11-Rad50-Nbs1 DNA repair complex and Tel1 (ATM) protein kinase.Nucleic acids research · 2025Article
- Structural basis for DNA break sensing by human MRE11-RAD50-NBS1 and its regulation by telomeric factor TRF2.Nature communications · 2025Article
- Mouse MRE11-RAD50-NBS1 is needed to start and extend meiotic DNA end resection.Nature communications · 2025Article
- Unusual clinical manifestations and predominant stopgain ATM gene variants in a single centre cohort of ataxia telangiectasia from North India.Scientific reports · 2022Article
- Loss of CENP-I Impairs Homologous Recombination and Sensitizes Cells to PARP1 Inhibition.Cancers · 2021Article
- Nbs1-mediated DNA damage repair pathway regulates haematopoietic stem cell development and embryonic haematopoiesis.Cell proliferation · 2021Article
- ATM Paradoxically Promotes Oncogenic Transformation via Transcriptional Reprogramming.Cancer research · 2020Article
- IKKα Kinase Regulates the DNA Damage Response and Drives Chemo-resistance in Cancer.Molecular cell · 2019Article
- UFL1 promotes histone H4 ufmylation and ATM activation.Nature communications · 2019Article
- Xrs2 and Tel1 Independently Contribute to MR-Mediated DNA Tethering and Replisome Stability.Cell reports · 2018Article
- Vicenin-2: a potential radiosensitizer of non-small cell lung cancer cells.Molecular biology reports · 2018Article
- Ataxia-telangiectasia: A new remitting form with a peculiar transcriptome signature.Neurology. Genetics · 2018Article
- Generation of a novel, multi-stage, progressive, and transplantable model of plasma cell neoplasms.Scientific reports · 2016Article
- Defining ATM-Independent Functions of the Mre11 Complex with a Novel Mouse Model.Molecular cancer research : MCR · 2016Article
- The Rad50 hook domain regulates DNA damage signaling and tumorigenesis.Genes & development · 2014Article
- Exonuclease 1 is a critical mediator of survival during DNA double strand break repair in nonquiescent hematopoietic stem and progenitor cells.Stem cells (Dayton, Ohio) · 2014Article
- Cdc42 and aging of hematopoietic stem cells.Current opinion in hematology · 2013Review
- Mre11 regulates CtIP-dependent double-strand break repair by interaction with CDK2.Nature structural & molecular biology · 2012Article
- The p53 tumor suppressor protein regulates hematopoietic stem cell fate.Journal of cellular physiology · 2011Review
- The mef/elf4 transcription factor fine tunes the DNA damage response.Cancer research · 2011Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Genetic and cytologic data from Saccharomyces cerevisiae and mammals implicate the Mre11 complex, consisting of Mre11, Rad50, and Nbs1, as a sensor of DNA damage, and indicate that the complex influences the activity of ataxia-telangiectasia mutated (ATM) in the DNA damage response. Rad50(S/S) mice exhibit precipitous apoptotic attrition of hematopoietic cells. We generated ATM- and Chk2-deficient Rad50(S/S) mice and found that Rad50(S/S) cellular attrition was strongly ATM and Chk2 dependent. The hypomorphic Mre11(ATLD1) and Nbs1(Delta)(B) alleles conferred similar rescue of Rad50(S/S)-dependent hematopoietic failure. These data indicate that the Mre11 complex activates an ATM-Chk2-dependent apoptotic pathway. We find that apoptosis and cell cycle checkpoint activation are parallel outcomes of the Mre11 complex-ATM pathway. Conversely, the Rad50(S) mutation mitigated several phenotypic features of ATM deficiency. We propose that the Rad50(S) allele is hypermorphic for DNA damage signaling, and that the resulting constitutive low-level activation of the DNA damage response accounts for the partial suppression of ATM deficiency in Rad50(S/S) Atm(-/-) mice.
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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.