ArticleMolecular cell2011
ATR autophosphorylation as a molecular switch for checkpoint activation.
Article in Molecular cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers.
What it found
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Who cites it
168 citing papers in PubMed, 262 citations in OpenAlex.
- Molecular insights and therapeutic implications for the tumor suppressor role of LKB1 in non-small cell lung cancer.Cancer letters · 2026Review
- Mechanistic insights into phosphorylation-driven activation and therapeutic inhibition of human ATR-ATRIP.Nature structural & molecular biology · 2026Article
- Capturing ATR-ATRIP in the act of activation.Nature structural & molecular biology · 2026Article
- SPHINX31 acts as a SRPK1 inhibitor targeting the ATR/DNA-PKcs/CHK1 replicative checkpoint to inhibit cell growth in non-small cell lung cancer.Molecular oncology · 2026Article
- Lipid Conjugation of a Photoprotective Meadowfoam (Biomolecules · 2026Article
- Structural mechanism of TOPBP1 activating the ATR-ATRIP replication checkpoint kinase.Nature structural & molecular biology · 2026Article
- SYCP2 recruits HORMAD2 to chromosome axes for unsynapsed chromatin silencing and synapsis surveillance in meiosis.Nature communications · 2026Article
- Tilting the balance of life and death: navigating DNA replication stress in cancer therapy.Experimental & molecular medicine · 2026Review
- Article
- Overexpression of CDT1 inhibits cell cycle progression at S phase by interacting with the mini-chromosome maintenance complex and causes DNA damage.FEBS open bio · 2026Article
- Auranofin attenuates TOPBP1-mediated ATR replication stress response and improves chemotherapeutic response in breast tumor models.The Journal of clinical investigation · 2025Article
- Mechanistic insights into the monotherapy and combination potential of FEN1 inhibition in cancer therapy.Nucleic acids research · 2025Article
- Participants in Transcription-Replication Conflict and Their Role in Formation and Resolution of R-Loops.International journal of molecular sciences · 2025Review
- Article
- Targeting Topoisomerase I and DNA with LCS1269 Drives Glioblastoma Cell Death Despite ATM/Chk1/BRCA1/RAD51 Signaling Pathway Activation.International journal of molecular sciences · 2025Article
- DNA Damage and Replication Stress Checkpoints.Annual review of biochemistry · 2025Review
- Replication stress, microcephalic primordial dwarfism, and compromised immunity in ATRIP deficient patients.The Journal of experimental medicine · 2025Article
- Protein Phosphatase 2ACα Regulates ATR-Mediated Endogenous DNA Damage Response Against Microcephaly.Molecular neurobiology · 2025Article
- A TRilogy of ATR's Non-Canonical Roles Throughout the Cell Cycle and Its Relation to Cancer.Cancers · 2024Review
- The loss of DNA polymerase epsilon accessory subunits POLE3-POLE4 leads to BRCA1-independent PARP inhibitor sensitivity.Nucleic acids research · 2024Article
108 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 3 countries.
Funding
Abstract
The ataxia telangiectasia-mutated and Rad3-related (ATR) kinase is a master checkpoint regulator safeguarding the genome. Upon DNA damage, the ATR-ATRIP complex is recruited to sites of DNA damage by RPA-coated single-stranded DNA and activated by an elusive process. Here, we show that ATR is transformed into a hyperphosphorylated state after DNA damage, and that a single autophosphorylation event at Thr 1989 is crucial for ATR activation. Phosphorylation of Thr 1989 relies on RPA, ATRIP, and ATR kinase activity, but unexpectedly not on the ATR stimulator TopBP1. Recruitment of ATR-ATRIP to RPA-ssDNA leads to congregation of ATR-ATRIP complexes and promotes Thr 1989 phosphorylation in trans. Phosphorylated Thr 1989 is directly recognized by TopBP1 via the BRCT domains 7 and 8, enabling TopBP1 to engage ATR-ATRIP, to stimulate the ATR kinase, and to facilitate ATR substrate recognition. Thus, ATR autophosphorylation on RPA-ssDNA is a molecular switch to launch robust checkpoint response.
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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.