ArticleMolecular and cellular biology2005
ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 246 papers.
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Who cites it
246 citing papers in PubMed, 421 citations in OpenAlex.
- Germ line genetic NBN variation and predisposition to B-cell acute lymphoblastic leukemia in children.Blood · 2024Trial
- Viral rewiring of DDR signaling activates a pro-survival network that drives chemotherapy resistance.bioRxiv : the preprint server for biology · 2026Article
- The Landscape of BRCA1-Associated Post-Translational Modifications.Cell biology international · 2026Review
- 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
- Tel1 is recruited at chromosomal loop/axis contact sites to modulate meiotic DNA double-strand breaks interference.PLoS genetics · 2025Article
- Structural basis for DNA break sensing by human MRE11-RAD50-NBS1 and its regulation by telomeric factor TRF2.Nature communications · 2025Article
- DNA Damage and Replication Stress Checkpoints.Annual review of biochemistry · 2025Review
- Targeting DNA damage sensors for cancer therapy.DNA repair · 2025Review
- Review
- The histone acetyltransferase CBP participates in regulating the DNA damage response through ATM after double-strand breaks.Genome biology · 2025Article
- The Development of ATM Inhibitors in Cancer Therapy.Targeted oncology · 2025Review
- Targeting the DNA damage response in cancer.MedComm · 2024Review
- DNA cytosine methyltransferases differentially regulate genome-wide hypermutation and interhomolog recombination in Trichoderma reesei meiosis.Nucleic acids research · 2024Article
- Distinct regulation of ATM signaling by DNA single-strand breaks and APE1.Nature communications · 2024Article
- Rif2 interaction with Rad50 counteracts Tel1 functions in checkpoint signalling and DNA tethering by releasing Tel1 from MRX binding.Nucleic acids research · 2024Article
- CellTool: An Open-Source Software Combining Bio-Image Analysis and Mathematical Modeling for the Study of DNA Repair Dynamics.International journal of molecular sciences · 2023Article
- Dynamic Properties of the DNA Damage Response Mre11/Rad50 Complex.International journal of molecular sciences · 2023Review
- Ubiquitination Links DNA Damage and Repair Signaling to Cancer Metabolism.International journal of molecular sciences · 2023Review
- The Ku complex promotes DNA end-bridging and this function is antagonized by Tel1/ATM kinase.Nucleic acids research · 2023Article
- Virulence Factors of the Periodontal Pathogens: Tools to Evade the Host Immune Response and Promote Carcinogenesis.Microorganisms · 2023Review
186 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
ATM has a central role in controlling the cellular responses to DNA damage. It and other phosphoinositide 3-kinase-related kinases (PIKKs) have giant helical HEAT repeat domains in their amino-terminal regions. The functions of these domains in PIKKs are not well understood. ATM activation in response to DNA damage appears to be regulated by the Mre11-Rad50-Nbs1 (MRN) complex, although the exact functional relationship between the MRN complex and ATM is uncertain. Here we show that two pairs of HEAT repeats in fission yeast ATM (Tel1) interact with an FXF/Y motif at the C terminus of Nbs1. This interaction resembles nucleoporin FXFG motif binding to HEAT repeats in importin-beta. Budding yeast Nbs1 (Xrs2) appears to have two FXF/Y motifs that interact with Tel1 (ATM). In Xenopus egg extracts, the C terminus of Nbs1 recruits ATM to damaged DNA, where it is subsequently autophosphorylated. This interaction is essential for ATM activation. A C-terminal 147-amino-acid fragment of Nbs1 that has the Mre11- and ATM-binding domains can restore ATM activation in an Nbs1-depleted extract. We conclude that an interaction between specific HEAT repeats in ATM and the C-terminal FXF/Y domain of Nbs1 is essential for ATM activation. We propose that conformational changes in the MRN complex that occur upon binding to damaged DNA are transmitted through the FXF/Y-HEAT interface to activate ATM. This interaction also retains active ATM at sites of DNA damage.
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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.