ArticleThe Journal of biological chemistry2011
ATM protein-dependent phosphorylation of Rad50 protein regulates DNA repair and cell cycle control.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 91 citations in OpenAlex.
- Induced pluripotent stem cells from ataxia-telangiectasia recapitulate the cellular phenotype.Stem cells translational medicine · 2012Trial
- Insight into meiotic DNA end resection: Mechanisms and regulation.DNA repair · 2025Review
- L-arginine synergistic with 5-fluorouracil intervenes in DNA damage repair via the DNA-PKcs/ATM/ATR pathway in hepatocellular carcinoma cells.Acta biochimica et biophysica Sinica · 2025Article
- ATM inhibition exploits checkpoint defects and ATM-dependent double strand break repair in TP53-mutant glioblastoma.Nature communications · 2024Article
- Trypanosoma cruzi infection induces DNA double-strand breaks and activates DNA damage response pathway in host epithelial cells.Scientific reports · 2024Article
- Key molecular DNA damage responses of human cells to radiation.Frontiers in cell and developmental biology · 2024Review
- Deciphering the phospho-signature induced by hepatitis B virus in primary human hepatocytes.Frontiers in microbiology · 2024Article
- Effects of HSV-G47Δ Oncolytic Virus on Telomerase and Telomere Length Alterations in Glioblastoma Multiforme Cancer Stem Cells Under Hypoxia and Normoxia Conditions.Current cancer drug targets · 2024Article
- SETD2 Loss and ATR Inhibition Synergize to Promote cGAS Signaling and Immunotherapy Response in Renal Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Review
- Alternative telomere maintenance mechanism iniScience · 2023Article
- Cancer and Radiosensitivity Syndromes: Is Impaired Nuclear ATM Kinase Activity the Primum Movens?Cancers · 2022Review
- Relations between Structure and Zn(II) Binding Affinity Shed Light on the Mechanisms of Rad50 Hook Domain Functioning and Its Phosphorylation.International journal of molecular sciences · 2022Article
- LINE-1 expression in cancer correlates with p53 mutation, copy number alteration, and S phase checkpoint.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Local non-pituitary growth hormone is induced with aging and facilitates epithelial damage.Cell reports · 2021Article
- COMMD4 functions with the histone H2A-H2B dimer for the timely repair of DNA double-strand breaks.Communications biology · 2021Article
- Excision of mutagenic replication-blocking lesions suppresses cancer but promotes cytotoxicity and lethality in nitrosamine-exposed mice.Cell reports · 2021Article
- RAD50 deficiency is a predictor of platinum sensitivity in sporadic epithelial ovarian cancers.Molecular biomedicine · 2020Article
- A Disease-Causing Single Amino Acid Deletion in the Coiled-Coil Domain of RAD50 Impairs MRE11 Complex Functions in Yeast and Humans.Cell reports · 2020Article
- Stress-sensing in the human greying hair follicle: Ataxia Telangiectasia Mutated (ATM) depletion in hair bulb melanocytes in canities-prone scalp.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 4 countries.
Funding
Abstract
The Mre11/Rad50/NBN complex plays a central role in coordinating the cellular response to DNA double-strand breaks. The importance of Rad50 in that response is evident from the recent description of a patient with Rad50 deficiency characterized by chromosomal instability and defective ATM-dependent signaling. We report here that ATM (defective in ataxia-telangiectasia) phosphorylates Rad50 at a single site (Ser-635) that plays an important adaptor role in signaling for cell cycle control and DNA repair. Although a Rad50 phosphosite-specific mutant (S635G) supported normal activation of ATM in Rad50-deficient cells, it was defective in correcting DNA damage-induced signaling through the ATM-dependent substrate SMC1. This mutant also failed to correct radiosensitivity, DNA double-strand break repair, and an S-phase checkpoint defect in Rad50-deficient cells. This was not due to disruption of the Mre11/Rad50/NBN complex revealing for the first time that phosphorylation of Rad50 plays a key regulatory role as an adaptor for specific ATM-dependent downstream signaling through SMC1 for DNA repair and cell cycle checkpoint control in the maintenance of genome integrity.
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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.