Affinage

ATR

Serine/threonine-protein kinase ATR · UniProt Q13535

Round 2 corrected
Length
2644 aa
Mass
301.4 kDa
Annotated
2026-04-28
130 papers in source corpus 37 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Insufficient on-target evidence to synthesize a narrative — discovery timeline does not match the canonical ATR protein.

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
No controlled-vocabulary terms were assigned to this entry.

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 ATRIP (ATR-interacting protein) directly binds RPA-coated ssDNA, and this interaction is required for recruitment of the ATR-ATRIP complex to sites of DNA damage and for ATR-mediated Chk1 activation. RPA stimulates ATRIP binding to ssDNA in vitro, and a checkpoint-deficient RPA mutant (rfa1-t11) is defective for recruiting the yeast homolog Ddc2 to ssDNA. In vitro binding assays, Co-IP, RNAi knockdown, yeast genetics with rfa1-t11 mutant Science High 12791985
2001 ATR and ATRIP are mutually dependent partners: ATRIP is phosphorylated by ATR, regulates ATR expression, and is essential for the DNA damage checkpoint pathway. Deletion of ATR causes loss of ATRIP expression, loss of checkpoint responses, and cell death, demonstrating ATR is essential for viability of human somatic cells. Cre-mediated conditional deletion, siRNA, Co-IP, immunofluorescence Science High 11721054
2001 ATR directly phosphorylates human Chk1 on serines 317 and 345 in vitro, and this phosphorylation is ATR-dependent in vivo in response to replication blocks and genotoxic stress. Chk1 S317A/S345A mutants show impaired activation and reduced ATR-mediated phosphorylation. In vitro kinase assay, site-directed mutagenesis, immunoprecipitation, gel filtration Molecular and cellular biology High 11390642
1999 ATR (and ATM) catalytic activity is directly inhibited by caffeine at concentrations that induce radiosensitization. ATR phosphorylates p53 on Ser15 in vivo, and caffeine inhibits this phosphorylation, implicating ATR as a direct upstream kinase for p53 Ser15 in response to UV and replication stress. In vitro kinase assay with immunoprecipitated ATR, cell-based checkpoint assays Cancer research High 10485486
1999 ATR phosphorylates p53 at Ser-15 and Ser-37 in vitro. Overexpression of kinase-inactive ATR (ATRki) in human fibroblasts inhibits Ser-15 phosphorylation in response to gamma-irradiation and UV, establishing ATR as a direct upstream regulator of p53 phosphorylation in DNA-damaged cells. In vitro kinase assay, dominant-negative overexpression, immunoblotting Genes & development High 9925639
1998 Overexpression of kinase-inactive ATR (ATRkd) causes sensitivity to ionizing radiation, cis-platinum, and hydroxyurea, and abrogates the G2/M checkpoint after IR, demonstrating that ATR kinase activity is required for multiple DNA damage checkpoint responses including the G2/M checkpoint. Dominant-negative overexpression, clonogenic survival, cell-cycle analysis The EMBO journal High 9427750
2006 TopBP1 directly activates the ATR-ATRIP kinase complex through a conserved ATR-activating domain (AAD) distinct from its BRCT repeats. Recombinant TopBP1 induces a large increase in ATR kinase activity in vitro; point mutation of the AAD in Xenopus egg extracts abolishes checkpoint regulation. Recombinant protein reconstitution, in vitro kinase assay, Xenopus egg extract, human cell expression Cell High 16530042
2008 ATRIP contains a TopBP1-interacting region necessary for TopBP1-ATR association and TopBP1-mediated ATR activation. ATR also contains a PIKK Regulatory Domain (PRD) adjacent to its kinase domain that is critical for activation by TopBP1 but not for basal kinase activity. This mechanism is conserved in yeast (Ddc2/Dpb11). Co-IP, in vitro kinase assay, site-directed mutagenesis, cellular complementation, yeast genetics Genes & development High 18519640
2016 ETAA1, containing dual RPA-binding motifs, provides an independent ATR activation pathway in vertebrates. ETAA1 accumulates at DNA damage sites via RPA interaction and contains a conserved domain that directly and potently stimulates ATR kinase activity independently of TopBP1. Simultaneous loss of ETAA1 and TopBP1 causes synthetic lethality with massive genome instability. Co-IP, in vitro kinase assay, RNAi/siRNA, immunofluorescence, mass spectrometry Nature cell biology High 27723717
2017 Cryo-EM structure of the human ATR-ATRIP complex at 4.7 Å resolution reveals a hollow 'heart' shape with two ATR monomers in distinct conformations and 14 HEAT repeats in ATRIP. The complex adopts pseudo 2-fold symmetry and the catalytic pockets face outward without inhibitory elements blocking substrate access. Cryo-electron microscopy, atomic model building Cell research High 29271416
2002 ATR, but not ATM, is critical for maintenance of common fragile site stability. ATR deficiency results in fragile site expression at metaphase chromosomes even without exogenous replication inhibitors, establishing that ATR monitors stalled replication forks at fragile sites. Dominant-negative ATR expression, cytogenetic analysis of metaphase chromosomes Cell High 12526805
2002 ATR preferentially binds UV-damaged DNA over undamaged DNA, and damaged DNA stimulates ATR kinase activity significantly more than undamaged DNA, suggesting ATR can function as an initial damage sensor. Purified ATR protein, in vitro DNA binding assays, electron microscopy, in vitro kinase assay Proceedings of the National Academy of Sciences Medium 12011431
2000 ATR regulates Chk1: overexpression of wild-type ATR enhances Chk1 Ser345 phosphorylation induced by UV, while kinase-defective ATR inhibits it. CHK1 knockout in mouse ES cells causes defective G2/M DNA damage checkpoint and peri-implantation embryonic lethality, placing Chk1 as an essential downstream effector of ATR. Gene disruption (knockout), conditional cell line, phospho-specific antibodies, overexpression Genes & development High 10859164
2001 ATR phosphorylates histone H2AX in an ATR-dependent but ATM-independent manner in response to replication inhibition by hydroxyurea or UV irradiation. Phospho-H2AX foci colocalize with PCNA, BRCA1, and 53BP1 at arrested replication forks in S phase cells. ATM-deficient cells, Hus1 mutant cells, ATR dominant-negative expression, immunofluorescence co-localization The Journal of biological chemistry High 11673449
2013 ATR prevents 'replication catastrophe' by two mechanistically coupled functions: locally protecting stalled forks and globally suppressing dormant origin firing. In ATR-deficient cells, unscheduled origin firing generates excess ssDNA that exhausts the nuclear RPA pool, causing nucleus-wide fork breakage. Forced elevation of RPA delayed replication catastrophe even without ATR activity. ATR inhibition, RPA manipulation (depletion and overexpression), single-molecule DNA fiber assay, live-cell imaging Cell High 24267891
2000 ATR phosphorylates BRCA1 on six Ser/Thr residues including Ser1423 in vitro, and phosphorylation on Ser1423 in vivo is ATR-dependent in response to HU or UV. ATR forms distinct nuclear foci at stalled replication forks that overlap with BRCA1 foci, placing ATR and BRCA1 in the same genotoxic stress-responsive pathway. In vitro kinase assay, doxycycline-inducible dominant-negative ATR, immunofluorescence co-localization, phospho-specific antibodies Genes & development High 11114888
2005 Conserved carboxy-terminal motifs in ATRIP (and Nbs1, Ku80) are required for interaction with ATR (and ATM, DNA-PKcs respectively), and are essential for efficient recruitment of ATR to sites of damage and for ATR-mediated checkpoint signaling. Co-IP, mutagenesis, laser-induced DNA damage with live imaging, checkpoint signaling assays Nature High 15758953
2018 ATR enforces an intrinsic S/G2 checkpoint by being activated by ETAA1 during normal DNA replication to block CDK1-directed FOXM1 phosphorylation until S phase ends. ATR inhibition prematurely activates FOXM1, leading to early mitosis, underreplicated DNA, and DNA damage. Live-cell imaging (CDK1-FOXM1 fluorescent reporters), ATR inhibition, ETAA1 depletion, cell cycle analysis Science High 30139873
2017 ATR promotes homologous recombination (HR) post-resection by stimulating the BRCA1-PALB2 interaction and promoting PALB2 localization to DNA damage sites. ATR phosphorylates PALB2 at S59 (promoting HR) while inhibiting CDK-mediated S64 phosphorylation (inhibitory to HR), orchestrating a 'CDK-to-ATR switch' that couples checkpoint signaling to HR. Co-IP, phospho-mutant analysis (S59A/S64E and S59E/S64A), HR reporter assay, immunofluorescence Molecular cell High 28089683
2004 Nbs1 (defective in Nijmegen breakage syndrome) facilitates ATR-dependent phosphorylation of Chk1, c-jun and p53 in response to UV and hydroxyurea-induced replication stalling. NBS cells also show impaired ubiquitination of FANCD2 (ATR-dependent) and fail to retain ATR in the nucleus after HU treatment. NBS patient cell lines, phospho-specific antibodies, nuclear fractionation, G2/M checkpoint assay The EMBO journal Medium 15616588
2002 Under severe hypoxia, ATR is activated by replication arrest (not DNA lesions) and phosphorylates p53 on Ser15, promoting p53 accumulation only in S-phase cells. Inhibition of ATR kinase activity substantially reduces hypoxia-induced p53 phosphorylation and p53 accumulation. Dominant-negative ATR expression, hypoxia treatment, phospho-specific immunoblotting, cell cycle synchronization Molecular and cellular biology Medium 11865061
2021 TopBP1 self-assembles into micrometer-sized condensates (liquid-liquid phase separation) that function as a molecular switch to amplify ATR kinase activity and phosphorylate Chk1. Single amino acid substitutions in the intrinsically disordered ATR activation domain disrupt TopBP1 condensation and abolish ATR/Chk1 signaling. Optogenetics, live-cell imaging, in vitro LLPS assay with purified TopBP1, mutagenesis, Chk1 phosphorylation assays Molecular cell High 33503405
2019 ETAA1 and TOPBP1 activate ATR through similar mechanisms involving a conserved predicted coiled-coil motif within their ATR activation domains (AADs). Mutation of the predicted coiled coils impairs AAD binding to ATR without affecting AAD oligomerization, suggesting a shared binding mechanism for ATR activation. Bioinformatics, in vitro kinase assay, co-immunoprecipitation, immunofluorescence signaling assays The Journal of biological chemistry Medium 30940728
2019 Quantitative phosphoproteomics reveals that TOPBP1 is the primary ATR activator during replication stress, while ETAA1-mediated ATR activation predominantly regulates mitotic ATR signaling. ATR activation by ETAA1 is required for Aurora B kinase activity during mitosis and for proper chromosome alignment and spindle assembly checkpoint response. Quantitative mass spectrometry phosphoproteomics, kinase activity assays, live-cell imaging, mitotic chromosome alignment assays The Journal of cell biology High 30755469
2020 ATR-mediated FANCI phosphorylation on Ser556, Ser559, and Ser565 stabilizes FANCI association with DNA and FANCD2, stimulating mono-ubiquitination of both FANCI and FANCD2 while also protecting the ubiquitinated complex from deubiquitination by USP1:UAF1. S559 and S565 are particularly important for protection from deubiquitination. Biochemical reconstitution with recombinant proteins, in vitro ATR kinase assay, phosphomimetic/phosphodead mutants, deubiquitination assays Frontiers in cell and developmental biology High 32117957
2003 ATR phosphorylates both p53 and Chk1 in response to extreme hypoxia, while ATM is not required for this response. In contrast, ATM (not ATR) mediates phosphorylation of these targets during reoxygenation-induced DNA damage. DNA structure-specific activities of ATR vs ATM are thus dictated by the type of stress (replication arrest vs. oxidative DNA damage). ATM-deficient cells, ATR inhibition with caffeine/wortmannin, comet assay, phospho-specific antibodies, NAC antioxidant rescue The Journal of biological chemistry Medium 12519769
2004 Regulation of Chk1 by ATR involves relief of autoinhibition: the C-terminal autoinhibitory region (AIR) of Xenopus Chk1 interacts intramolecularly with the kinase domain. ATR-mediated phosphorylation of the ATR phosphorylation domain linked to the AIR disrupts this autoinhibitory interaction, resulting in Chk1 activation. Domain mapping, co-expression in Xenopus oocytes/embryos, in vitro binding assays, phospho-mimic mutations Molecular biology of the cell Medium 14767054
2013 DNA-PKcs primes ATR/Chk1 activation at replication-born DSBs through structure-specific phosphorylation of RPA32 and TopBP1. The juxtaposition of a double-stranded DNA end and a short ssDNA gap robustly activates ATR and Chk1 in human cell-free extracts; this response depends on both DNA-PKcs and ATR congregating on gapped linear duplex DNA. Human cell-free extract, defined DNA substrates, immunodepletion, phospho-specific antibodies The Journal of cell biology Medium 23897887
2023 ATR is active in micronuclei (MN) during S phase and promotes MN rupture by phosphorylating Lamin A/C at Ser395, which primes subsequent CDK1-mediated phosphorylation at Ser392, thereby destabilizing the MN envelope. ATR inhibition reduces MN rupture, compromises cGAS activation, and impairs cGAS-dependent clearance of micronuclear DNA and immunosurveillance by NK cells. Live-cell imaging, phospho-specific antibodies, ATR and CDK1 inhibitors, cGAS reporter assays, NK cell killing assays, Lamin A/C mutagenesis Molecular cell High 37788673
2017 Nuclear phosphoinositide lipids (PPIs), particularly PIP3 in complex with the nuclear receptor SF1, are required for ATR recruitment to DNA damage sites. PPI accumulation at damage sites requires IPMK-mediated phosphorylation and promotes nuclear actin assembly that is necessary for ATR recruitment. Sequestration of PPIs blocks ATR but not ATM or DNA-PKcs recruitment/activation. Nuclear-targeted PH domain expression, live-cell imaging, ATR/Chk1 activation assays, latrunculin A and wortmannin treatment, IPMK/SF1 depletion Nature communications Medium 29242514
2003 ATR associates with mouse meiotic prophase chromosome cores and synaptonemal complexes, forming dense aggregates on chromosomes that are last to pair at the zygotene-pachytene transition. ATR distribution in meiosis is distinct from RAD51/DMC1 recombinase foci, suggesting a role in signaling pairing delays rather than at recombination sites directly. Immunofluorescence on spread spermatocytes, electron microscopy, co-localization analysis Chromosoma Medium 10382071
2023 ATR protects ongoing and newly assembled replication forks through distinct mechanisms: at ongoing forks, ATR prevents MRE11/EXO1-mediated degradation from PrimPol-generated ssDNA gaps and limits fork uncoupling; at new forks, ATR blocks MRE11/CtIP-initiated template DNA degradation by EXO1. ATR inhibition preferentially exacerbates gap-dependent nascent DNA degradation in BRCA1/2-deficient cells. DNA fiber assay, electron microscopy, PrimPol depletion, EXO1/MRE11/CtIP inhibition/depletion, ATR inhibitor Cell reports High 37454295
2003 A synonymous splicing mutation in ATR causes Seckel syndrome (intrauterine growth retardation, dwarfism, microcephaly). Patient fibroblasts display defective DNA damage response due to impaired ATR function, demonstrating that ATR hypomorphic mutations cause a human developmental disorder. Genetic mapping, sequencing, splicing analysis, functional cell-based DNA damage response assays in patient fibroblasts Nature genetics High 12640452
2007 RPA and ATR mediate p53 Ser15 phosphorylation in response to transcription blockade (independently of DNA replication). Inhibition of elongating RNA polymerase II leads to RPA- and ATR-dependent p53 phosphorylation, revealing an ATR-mediated transcriptional stress response that does not require DNA damage. Anti-RNA Pol II microinjection, replication inhibitors (aphidicolin), ATR inhibition, phospho-p53 immunoblotting Proceedings of the National Academy of Sciences Medium 17616578
1999 ATR kinase activity is inhibited by wortmannin at higher concentrations (IC50 ~1.8 µM) than required for ATM or DNA-PK inhibition, distinguishing ATR pharmacologically from other PIKK family members. In vitro kinase assay with immunoprecipitated ATR, dose-response analysis Cancer research Medium 9766667
2020 ATR mediates the cellular response to partial CDC7 inhibition primarily through ETAA1. Upon CDC7 inhibition, ATR restricts origin firing; subsequent ATR inhibition unleashes CDK- and CDC7-dependent origin firing driving cells into premature defective mitosis. This establishes the ETAA1-ATR axis as the origin firing checkpoint during CDC7 inhibition. CRISPR-Cas9 genome-wide screen, ETAA1/TOPBP1 co-depletion, ATR inhibitor, DNA fiber assay, cell cycle analysis Cell reports Medium 32877678
2023 ADAR1 (nuclear form) promotes ATR activation by interacting with TOPBP1 and facilitating its loading onto perturbed replication forks by enhancing TOPBP1 association with the 9-1-1 complex subunit RAD9. DNA-RNA hybrids (R-loops) compete with TOPBP1 for ADAR1 binding, causing ADAR1 translocation to R-loop regions where it recruits RNA helicases DHX9/DDX21 to resolve R-loops, simultaneously freeing TOPBP1 to stimulate ATR. Co-IP, proximity ligation assay, chromatin fractionation, R-loop immunoprecipitation, ATR/Chk1 signaling assays Nucleic acids research Medium 37831098

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science (New York, N.Y.) 2197 12791985
1998 Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science (New York, N.Y.) 1694 9733515
2000 Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. Genes & development 1375 10859164
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
2013 DNA damage sensing by the ATM and ATR kinases. Cold Spring Harbor perspectives in biology 1143 24003211
1998 The complexity of p53 modulation: emerging patterns from divergent signals. Genes & development 1121 9765199
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2010 The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer. Advances in cancer research 1019 21034966
2004 Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Molecular cell 1014 15149599
2005 Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature 996 15758953
2001 Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress. The Journal of biological chemistry 961 11673449
2005 Nucleolar proteome dynamics. Nature 934 15635413
1999 Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine. Cancer research 919 10485486
2001 ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1. Molecular and cellular biology 909 11390642
1999 A role for ATR in the DNA damage-induced phosphorylation of p53. Genes & development 852 9925639
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2005 Rheb binds and regulates the mTOR kinase. Current biology : CB 795 15854902
2001 ATR and ATRIP: partners in checkpoint signaling. Science (New York, N.Y.) 791 11721054
2002 Directed proteomic analysis of the human nucleolus. Current biology : CB 780 11790298
2013 ATR prohibits replication catastrophe by preventing global exhaustion of RPA. Cell 752 24267891
2000 The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Genes & development 725 10673501
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2000 Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro. Proceedings of the National Academy of Sciences of the United States of America 700 10973490
2012 A census of human soluble protein complexes. Cell 689 22939629
1999 Substrate specificities and identification of putative substrates of ATM kinase family members. The Journal of biological chemistry 679 10608806
2017 The essential kinase ATR: ensuring faithful duplication of a challenging genome. Nature reviews. Molecular cell biology 658 28811666
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2000 The many substrates and functions of ATM. Nature reviews. Molecular cell biology 631 11252893
2003 A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome. Nature genetics 621 12640452
2006 TopBP1 activates the ATR-ATRIP complex. Cell 616 16530042
1996 Regulation of RAD53 by the ATM-like kinases MEC1 and TEL1 in yeast cell cycle checkpoint pathways. Science (New York, N.Y.) 545 8553072
1998 A Mec1- and Rad53-dependent checkpoint controls late-firing origins of DNA replication. Nature 538 9783589
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
2001 ATM and ATR: networking cellular responses to DNA damage. Current opinion in genetics & development 509 11163154
2014 ATM and ATR as therapeutic targets in cancer. Pharmacology & therapeutics 504 25512053
1998 Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin. Cancer research 485 9766667
1998 Overexpression of a kinase-inactive ATR protein causes sensitivity to DNA-damaging agents and defects in cell cycle checkpoints. The EMBO journal 475 9427750
2002 ATR regulates fragile site stability. Cell 471 12526805
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2000 Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress. Genes & development 410 11114888
2008 TopBP1 activates ATR through ATRIP and a PIKK regulatory domain. Genes & development 291 18519640
2017 ATR/CHK1 inhibitors and cancer therapy. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 282 29054375
2003 DNA polymerase stabilization at stalled replication forks requires Mec1 and the RecQ helicase Sgs1. The EMBO journal 280 12912929
2018 Targeting ATR in cancer. Nature reviews. Cancer 267 29899559
2002 Hypoxia links ATR and p53 through replication arrest. Molecular and cellular biology 251 11865061
2018 An intrinsic S/G2 checkpoint enforced by ATR. Science (New York, N.Y.) 242 30139873
1999 MEC1 and MEC2: two new cell lines derived from B-chronic lymphocytic leukaemia in prolymphocytoid transformation. Leukemia research 237 10071128
2003 ATR/ATM targets are phosphorylated by ATR in response to hypoxia and ATM in response to reoxygenation. The Journal of biological chemistry 236 12519769
1999 Interactions of TLC1 (which encodes the RNA subunit of telomerase), TEL1, and MEC1 in regulating telomere length in the yeast Saccharomyces cerevisiae. Molecular and cellular biology 228 10454554
2010 ATR: a master conductor of cellular responses to DNA replication stress. Trends in biochemical sciences 226 20947357
2015 Molecular Pathways: Targeting ATR in Cancer Therapy. Clinical cancer research : an official journal of the American Association for Cancer Research 219 26362996
2018 SLFN11 Blocks Stressed Replication Forks Independently of ATR. Molecular cell 212 29395061
2007 The ATR pathway: fine-tuning the fork. DNA repair 202 17531546
2016 Activation of the ATR kinase by the RPA-binding protein ETAA1. Nature cell biology 200 27723717
2005 Saccharomyces cerevisiae Rad9 acts as a Mec1 adaptor to allow Rad53 activation. Current biology : CB 194 16085488
2015 ATM and ATR signaling at a glance. Journal of cell science 193 26567218
2017 Targeting the ATR-CHK1 Axis in Cancer Therapy. Cancers 184 28448462
2013 Targeting ATR in DNA damage response and cancer therapeutics. Cancer treatment reviews 157 23583268
2017 Coupling of Homologous Recombination and the Checkpoint by ATR. Molecular cell 153 28089683
2007 ATM and ATR: components of an integrated circuit. Cell cycle (Georgetown, Tex.) 151 17312392
2004 Nbs1 is required for ATR-dependent phosphorylation events. The EMBO journal 144 15616588
2002 Preferential binding of ATR protein to UV-damaged DNA. Proceedings of the National Academy of Sciences of the United States of America 132 12011431
2010 The ATR barrier to replication-born DNA damage. DNA repair 120 21036674
2009 ATR/Mec1: coordinating fork stability and repair. Current opinion in cell biology 117 19230642
2017 APOBEC3A and APOBEC3B Activities Render Cancer Cells Susceptible to ATR Inhibition. Cancer research 113 28698210
2011 Dpb11 coordinates Mec1 kinase activation with cell cycle-regulated Rad9 recruitment. The EMBO journal 104 21946560
2007 RPA and ATR link transcriptional stress to p53. Proceedings of the National Academy of Sciences of the United States of America 104 17616578
2021 Progress towards a clinically-successful ATR inhibitor for cancer therapy. Current research in pharmacology and drug discovery 101 34909652
2008 Dpb11 activates the Mec1-Ddc2 complex. Proceedings of the National Academy of Sciences of the United States of America 101 19028869
2016 Radiosensitization by the ATR Inhibitor AZD6738 through Generation of Acentric Micronuclei. Molecular cancer therapeutics 97 28062704
2015 Phosphoproteomics reveals distinct modes of Mec1/ATR signaling during DNA replication. Molecular cell 93 25752575
2020 Advanced Prostate Cancer with ATM Loss: PARP and ATR Inhibitors. European urology 92 33176972
2021 TopBP1 assembles nuclear condensates to switch on ATR signaling. Molecular cell 90 33503405
2015 Cancer-Specific Synthetic Lethality between ATR and CHK1 Kinase Activities. Cell reports 90 26748709
2018 Synthetically Lethal Interactions of ATM, ATR, and DNA-PKcs. Trends in cancer 88 30352678
2004 ATM and ATR: sensing DNA damage. World journal of gastroenterology 87 14716813
2005 The DNA damage-inducible UbL-UbA protein Ddi1 participates in Mec1-mediated degradation of Ho endonuclease. Molecular and cellular biology 85 15964793
2019 A consensus set of genetic vulnerabilities to ATR inhibition. Open biology 84 31506018
2017 Cryo-EM structure of human ATR-ATRIP complex. Cell research 81 29271416
2017 DNA damage causes rapid accumulation of phosphoinositides for ATR signaling. Nature communications 79 29242514
1999 The association of ATR protein with mouse meiotic chromosome cores. Chromosoma 79 10382071
2005 The conserved Mec1/Rad53 nuclear checkpoint pathway regulates mitochondrial DNA copy number in Saccharomyces cerevisiae. Molecular biology of the cell 78 15829566
2024 Targeting ATR in patients with cancer. Nature reviews. Clinical oncology 72 38378898
2017 Formation of a Snf1-Mec1-Atg1 Module on Mitochondria Governs Energy Deprivation-Induced Autophagy by Regulating Mitochondrial Respiration. Developmental cell 72 28399401
2006 ATR homolog Mec1 controls association of DNA polymerase zeta-Rev1 complex with regions near a double-strand break. Current biology : CB 67 16546083
2005 Frp1 is a Fusarium oxysporum F-box protein required for pathogenicity on tomato. Molecular microbiology 67 16091043
2004 Regulation of Chk1 kinase by autoinhibition and ATR-mediated phosphorylation. Molecular biology of the cell 67 14767054
2016 Efficacy of ATR inhibitors as single agents in Ewing sarcoma. Oncotarget 66 27577084
2017 DNA-PKcs, ATM, and ATR Interplay Maintains Genome Integrity during Neurogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience 60 28123024
2017 Structural Basis of Mec1-Ddc2-RPA Assembly and Activation on Single-Stranded DNA at Sites of Damage. Molecular cell 60 29033322
2020 BRG1 Loss Predisposes Lung Cancers to Replicative Stress and ATR Dependency. Cancer research 57 32690724
2008 Activation of ATR and related PIKKs. Cell cycle (Georgetown, Tex.) 57 18769153
2023 Targeting ATM and ATR for cancer therapeutics: Inhibitors in clinic. Drug discovery today 56 37302542
2012 Germline mutation in ATR in autosomal- dominant oropharyngeal cancer syndrome. American journal of human genetics 55 22341969
2016 TPP1 Blocks an ATR-Mediated Resection Mechanism at Telomeres. Molecular cell 53 26778124
2022 Guiding ATR and PARP inhibitor combinationswith chemogenomic screens. Cell reports 52 35830811
2021 An extending ATR-CHK1 circuitry: the replication stress response and beyond. Current opinion in genetics & development 52 34329853
2019 Temozolomide Sensitizes MGMT-Deficient Tumor Cells to ATR Inhibitors. Cancer research 51 31273061
2014 Yeast PP4 interacts with ATR homolog Ddc2-Mec1 and regulates checkpoint signaling. Molecular cell 51 25533186
2019 Quantitative phosphoproteomics reveals mitotic function of the ATR activator ETAA1. The Journal of cell biology 50 30755469
2023 ATR promotes clearance of damaged DNA and damaged cells by rupturing micronuclei. Molecular cell 47 37788673
2003 Hyperoxia activates the ATR-Chk1 pathway and phosphorylates p53 at multiple sites. American journal of physiology. Lung cellular and molecular physiology 47 12959929
2023 Emerging strategies for cancer therapy by ATR inhibitors. Cancer science 46 37189251
2022 TOP1-DNA Trapping by Exatecan and Combination Therapy with ATR Inhibitor. Molecular cancer therapeutics 42 35439320
2019 Activation of ATR-related protein kinase upon DNA damage recognition. Current genetics 42 31624858
2014 Homeostatic regulation of meiotic DSB formation by ATM/ATR. Experimental cell research 42 25116420
2009 Mutation of CRE1 in Fusarium oxysporum reverts the pathogenicity defects of the FRP1 deletion mutant. Molecular microbiology 42 19912543
2010 Mechanisms of ATR-mediated checkpoint signalling. Frontiers in bioscience (Landmark edition) 40 20515729
2004 The ATR-p53 pathway is suppressed in noncycling normal and malignant lymphocytes. Oncogene 40 14755251
2016 ATR-mediated regulation of nuclear and cellular plasticity. DNA repair 38 27283761
2005 ARF and ATM/ATR cooperate in p53-mediated apoptosis upon oncogenic stress. Biochemical and biophysical research communications 38 16004968
1999 Drosophila dSmad2 and Atr-I transmit activin/TGFbeta signals. Genes to cells : devoted to molecular & cellular mechanisms 38 10320478
2015 Wee1 is required to sustain ATR/Chk1 signaling upon replicative stress. Oncotarget 37 25965828
2006 How cells activate ATR. Cell cycle (Georgetown, Tex.) 36 16760665
2020 ATR Restrains DNA Synthesis and Mitotic Catastrophe in Response to CDC7 Inhibition. Cell reports 35 32877678
2013 DNA structure-specific priming of ATR activation by DNA-PKcs. The Journal of cell biology 35 23897887
2007 Meiotic roles of Mec1, a budding yeast homolog of mammalian ATR/ATM. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 34 17674144
2019 Common motifs in ETAA1 and TOPBP1 required for ATR kinase activation. The Journal of biological chemistry 33 30940728
2008 ATR and Rad17 collaborate in modulating Rad9 localisation at sites of DNA damage. Journal of cell science 32 19020305
2014 RNA-processing proteins regulate Mec1/ATR activation by promoting generation of RPA-coated ssDNA. EMBO reports 31 25527408
2020 ATR-Mediated FANCI Phosphorylation Regulates Both Ubiquitination and Deubiquitination of FANCD2. Frontiers in cell and developmental biology 30 32117957
2023 ATR protects ongoing and newly assembled DNA replication forks through distinct mechanisms. Cell reports 29 37454295
2014 Identification of ATR-Chk1 pathway inhibitors that selectively target p53-deficient cells without directly suppressing ATR catalytic activity. Cancer research 29 25336189
2009 Mouse models for ATR deficiency. DNA repair 29 19782648
2016 IGF-1R inhibition sensitizes breast cancer cells to ATM-related kinase (ATR) inhibitor and cisplatin. Oncotarget 27 27472395
2015 Senataxin controls meiotic silencing through ATR activation and chromatin remodeling. Cell discovery 26 27462424
1999 Interaction between the MEC1-dependent DNA synthesis checkpoint and G1 cyclin function in Saccharomyces cerevisiae. Genetics 26 9927443
2023 ADAR1 links R-loop homeostasis to ATR activation in replication stress response. Nucleic acids research 25 37831098
2004 DNA stimulates Mec1-mediated phosphorylation of replication protein A. The Journal of biological chemistry 25 15078888