Affinage

ATRIP

ATR-interacting protein · UniProt Q8WXE1

Length
791 aa
Mass
85.8 kDa
Annotated
2026-06-09
50 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATRIP is the obligate regulatory partner of the ATR kinase, and the two proteins are mutually dependent for stable expression and for mounting DNA damage checkpoint responses (PMID:11721054). ATRIP localizes the complex to sites of genotoxic stress: its N-terminal checkpoint recruitment domain (CRD) directly binds RPA-coated ssDNA, the structure that recruits ATR-ATRIP to DNA damage and stimulates downstream checkpoint kinase activity (PMID:12791985, PMID:17339343). RPA-ssDNA engagement is mediated by multiple, redundant interactions flanking the conserved coiled-coil, which itself drives ATRIP homo-oligomerization required for stable ATR binding and accumulation at lesions; oligomerization per se, rather than the specific coiled-coil sequence, is the essential feature (PMID:16027118, PMID:16407120). Structurally, ATR-ATRIP assembles as a heart-shaped dimer of heterodimers in which an extended HEAT-repeat ATRIP locks the N-termini of two ATR monomers (PMID:29271416). Once recruited, the complex is allosterically activated by TopBP1, which engages a dedicated TopBP1-interacting region in ATRIP that cooperates with the ATR PIKK regulatory domain (PRD) to switch on kinase activity, enabling phosphorylation of Chk1 and other substrates (PMID:16530042, PMID:18519640). Distinct ATRIP domains route the complex to distinct outputs: the RPA-binding region supports FANCD2 monoubiquitination and FANCI phosphorylation in the Fanconi anemia pathway, whereas full Chk1 activation requires both the RPA- and TopBP1-binding regions (PMID:22258451). ATRIP activity is further tuned by post-translational modifications, including CDK2-cyclin A phosphorylation at S224 controlling G2/M checkpoint maintenance, SIRT2-dependent K32 deacetylation promoting RPA-ssDNA binding, and SUMO2/3 modification at K234/K289 enabling coordinated assembly with ATR, RPA, TopBP1, and MRN (PMID:17638878, PMID:26854234, PMID:24990965), and by interacting partners that act as positive regulators (Nek1, ZFP161) or as a negative regulator (REV7, which directly binds ATRIP to inhibit ATR kinase activity) (PMID:23345434, PMID:31757956, PMID:41562258).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2001 High

    Established that ATR does not function alone but requires a dedicated partner, defining ATRIP as the obligate co-factor of ATR.

    Evidence Co-immunoprecipitation, siRNA knockdown, and checkpoint assays in human cells

    PMID:11721054

    Open questions at the time
    • Did not define how the complex is recruited to DNA
    • Did not map interaction surfaces or domains
  2. 2003 High

    Identified the physical signal that recruits ATR-ATRIP, showing RPA-coated ssDNA as the structure bound by ATRIP to localize the kinase to damage.

    Evidence In vitro RPA-ssDNA binding, in vivo recruitment assays, and yeast rfa1-t11 genetics

    PMID:12791985

    Open questions at the time
    • Did not localize the RPA-binding region within ATRIP
    • Did not establish whether RPA binding is sufficient for kinase activation
  3. 2004 High

    Dissected the biochemistry of ATR-ATRIP DNA binding and activation, showing ATRIP stimulates ssDNA-dependent substrate phosphorylation and that ssDNA/dsDNA junctions plus Claspin promote Chk1 activation.

    Evidence In vitro kinase and DNA-binding assays, Xenopus egg extract reconstitution, ATRIP phosphosite mapping (S68/S72)

    PMID:14724280 PMID:14729973 PMID:15371427 PMID:15451423

    Open questions at the time
    • RPA-independent low-affinity binding required an unidentified factor
    • Function of S68/S72 phosphorylation beyond foci accumulation unclear
  4. 2005 High

    Resolved the modular architecture of ATRIP, separating an N-terminal RPA-ssDNA-binding/foci-recruitment function from a coiled-coil oligomerization function required for stable ATR binding.

    Evidence Domain deletion and domain-swap mutants, Chk1 phosphorylation, foci and DNA fiber assays in human cells and egg extracts

    PMID:15527801 PMID:15743907 PMID:16027118 PMID:16176973 PMID:16186122

    Open questions at the time
    • Showed RPA binding is not strictly essential for Chk1 activation, leaving the activation trigger unresolved
    • Separable replication-fork vs. G2/M functions not mechanistically explained
  5. 2006 High

    Defined the allosteric activation mechanism, identifying TopBP1 as the direct kinase activator of ATR-ATRIP and mapping multiple redundant RPA-ssDNA contacts in ATRIP.

    Evidence In vitro kinase assays with recombinant TopBP1, point mutagenesis, domain mapping of RPA-ssDNA contacts

    PMID:16407120 PMID:16530042

    Open questions at the time
    • Did not identify the ATRIP region contacting TopBP1
    • Did not define the structural basis of activation
  6. 2007 High

    Pinpointed the conserved checkpoint recruitment domain (CRD) mediating RPA binding and a CDK2 phosphosite (S224) regulating the checkpoint, linking ATRIP function to cell-cycle control.

    Evidence NMR and mutagenesis of yeast Ddc2 CRD, CDK2-cyclin A kinase assays and S224A checkpoint assays

    PMID:17339343 PMID:17638878

    Open questions at the time
    • CRD/RPA disruption only partially compromised checkpoint signaling
    • TopBP1-mediated activation can bypass RPA binding
  7. 2008 High

    Mapped the ATRIP TopBP1-interacting region and showed it cooperates with the ATR PRD, providing the molecular basis for TopBP1-dependent kinase activation.

    Evidence Domain mapping, site-directed mutagenesis of ATR and ATRIP, in vitro kinase and cellular rescue, yeast epistasis

    PMID:18519640

    Open questions at the time
    • Structural mechanism of PRD-TopBP1 cooperation not yet resolved
  8. 2012 High

    Showed ATRIP domains route signaling to distinct outputs, with the RPA-binding region required for FANCD2/FANCI activation in the Fanconi anemia pathway.

    Evidence Conditional ATRIP-deficient DT40 cells, in vitro kinase assays on recombinant FANCI, domain deletion mutants

    PMID:22258451

    Open questions at the time
    • How FANCD2 facilitates FANCI phosphorylation mechanistically unclear
    • Did not address structural basis of domain-specific output
  9. 2013 High

    Expanded the regulatory network of ATRIP, identifying Nek1 and the FA core complex as positive regulators of ATRIP stability and chromatin loading, and BRCA1 BRCT binding to a phospho-ATRIP motif.

    Evidence Co-IP, siRNA knockdown, kinase assays, chromatin fractionation in DT40 cells, BRCA1-ATRIP phosphopeptide crystal structure with ITC

    PMID:23345434 PMID:23723247 PMID:24073851

    Open questions at the time
    • Functional role of BRCA1-ATRIP pS238 binding in vivo not established
    • FA core complex mechanism distinct from canonical RAD17/TOPBP1 not fully defined
  10. 2014 High

    Established SUMO2/3 modification of ATRIP as a coordinating switch that promotes simultaneous assembly with multiple partners at damage sites.

    Evidence SUMO site mapping (K234/K289), mutants, in vitro SUMO-binding, and SUMO2-fusion rescue

    PMID:24990965

    Open questions at the time
    • SUMO ligase responsible for ATRIP modification not identified
    • Quantitative contribution to checkpoint signaling unresolved
  11. 2016 High

    Added acetylation control, showing SIRT2-dependent K32 deacetylation promotes ATRIP recruitment, RPA-ssDNA binding, and replication fork recovery.

    Evidence In vitro deacetylation, K32R/K32Q mutants, foci, ATR autophosphorylation, and DNA fiber assays

    PMID:26854234

    Open questions at the time
    • Acetyltransferase opposing SIRT2 not identified
    • How K32 status alters RPA-ssDNA affinity structurally unknown
  12. 2017 High

    Provided the first structural views of ATR-ATRIP and the orthologous Mec1-Ddc2 as dimers of heterodimers, revealing how ATRIP organizes the complex and how the PRD imposes allosteric kinase regulation.

    Evidence Cryo-EM of human ATR-ATRIP (4.7 Å) and yeast Mec1-Ddc2 (3.9 Å); ATRIP-MCM interaction mapping by MS/pulldown

    PMID:29191911 PMID:29271416 PMID:29442041

    Open questions at the time
    • Limited resolution of human structure left ATRIP details incomplete
    • Functional significance of ATRIP-MCM interaction only partially defined
  13. 2019 Medium

    Identified ZFP161 as a scaffold that stabilizes the RPA-ATR-ATRIP assembly at stalled forks, extending the list of positive recruitment factors.

    Evidence Co-IP, domain mapping, ZFP161 knockout mice, ATR-Chk1 signaling assays

    PMID:31757956

    Open questions at the time
    • Single lab; structural basis of scaffolding undefined
    • Generality across damage types not established
  14. 2023 Medium

    Revealed an RPA-independent recruitment route, with APE1 directly recruiting ATRIP to ssDNA to activate the ATR-Chk1 pathway.

    Evidence In vitro pulldown, Xenopus egg extract reconstitution, APE1 N-terminal motif mutagenesis, Chk1 phosphorylation

    PMID:37216274

    Open questions at the time
    • Single lab; in vivo importance in human cells not established
    • Relationship to canonical RPA-dependent recruitment unclear
  15. 2025 High

    Identified REV7 as a direct negative regulator binding a defined ATRIP motif to inhibit ATR kinase activity, and produced near-atomic inhibitor-bound structures of the complex.

    Evidence In vitro binding and kinase assays, REV7-interaction motif mutagenesis, cellular CHK1 assays; cryo-EM at ~3 Å with VE-822 and RP-3500

    PMID:40379520 PMID:41562258

    Open questions at the time
    • Cellular conditions governing REV7-mediated inhibition not fully defined
    • How inhibitor binding relates to physiological activation states partially resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple ATRIP recruitment routes (RPA-dependent, APE1-dependent, FA-complex-dependent) and the layered PTMs and partner interactions are integrated to set ATR activity thresholds in vivo remains unresolved.
  • No unified quantitative model of recruitment vs. activation
  • Spatiotemporal hierarchy of PTMs and partner binding not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 3 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-73894 DNA Repair 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-1640170 Cell Cycle 2
Partners
ATRBRCA1MCM2NEK1REV7RPA70TOPBP1ZFP161
Complex memberships
ATR-ATRIP

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 ATRIP is an ATR-interacting protein that is phosphorylated by ATR, regulates ATR expression, and is mutually dependent with ATR for stable expression; siRNA knockdown of ATRIP causes loss of both ATRIP and ATR protein and abolishes DNA damage checkpoint responses, establishing ATR and ATRIP as obligate partners. Co-immunoprecipitation, siRNA knockdown, Cre-mediated ATR deletion, checkpoint assays Science High 11721054
2003 RPA-coated ssDNA is the critical structure that recruits the ATR-ATRIP complex to sites of DNA damage; ATRIP directly binds RPA-ssDNA in vitro, enabling ATR-ATRIP to associate with DNA and stimulate phosphorylation of Rad17; the yeast ATRIP ortholog Ddc2 is recruited to DSBs in an RPA-dependent manner, and the checkpoint-deficient RPA mutant rfa1-t11 is defective for recruiting Ddc2 both in vivo and in vitro. In vitro RPA-ssDNA binding assays, in vivo chromatin recruitment assays, checkpoint kinase assays, yeast genetics with rfa1-t11 mutant Science High 12791985
2004 ATR exists as a monomer associated with ATRIP with moderate affinity; ATRIP stimulates ATR-mediated phosphorylation of RPA in a ssDNA-dependent manner, but both ATR alone and the ATR-ATRIP heterodimer bind naked or RPA-covered DNA with comparable affinities. In vitro kinase assays, DNA-binding assays, biochemical fractionation Molecular and cellular biology Medium 14729973
2004 ATR-ATRIP complex can bind ssDNA in two modes: a high-affinity RPA-dependent mode and a lower-affinity RPA-independent mode that requires an additional unidentified protein from HeLa nuclear extract; neither ATR nor ATRIP can bind DNA individually in this low-affinity mode. ssDNA-cellulose pulldown, chromatin association assays, nuclear extract complementation The Journal of biological chemistry Medium 14724280
2004 ATR-mediated phosphorylation of ATRIP at Ser-68 and Ser-72 occurs in response to genotoxic stimuli; phosphorylated ATRIP accumulates at DNA damage foci, but this phosphorylation is dispensable for ATRIP relocalization to foci and activation of downstream effectors. Mass spectrometry, phospho-specific antibodies, in vitro kinase assay, immunofluorescence Biochemical and biophysical research communications Medium 15451423
2004 ATR-ATRIP and Claspin collaborate in a multistep process for Chk1 activation: ATR-ATRIP bound to ssDNA/dsDNA junction templates shows higher kinase activity than on ssDNA alone, and Claspin strongly stimulates phosphorylation of Chk1 by activated ATR-ATRIP. Xenopus egg extract cell-free reconstitution, kinase assays with defined DNA templates, immunodepletion The Journal of biological chemistry High 15371427
2004 The N-terminal domain of ATRIP contributes to intranuclear relocalization to DNA damage-induced foci in an RPA-dependent manner even without ATR association, suggesting an ATR-independent localization function for this domain. Domain deletion/truncation constructs, immunofluorescence foci assays, co-immunoprecipitation FEBS letters Medium 15527801
2005 The N-terminal domain of ATRIP is necessary and sufficient for interaction with RPA-ssDNA and for ATRIP accumulation into damage-induced foci; however, the ATRIP-RPA-ssDNA interaction is not absolutely essential for ATR activation because Chk1 phosphorylation occurs in cells expressing an ATRIP mutant that cannot bind RPA-ssDNA; ATR association is also required for proper ATRIP localization. Domain deletion mutants, immunofluorescence foci assays, Chk1 phosphorylation assays, complementation in ATRIP-depleted cells Molecular biology of the cell High 15743907
2005 ATRIP binding to ATR is required for ATR to efficiently phosphorylate Chk1 in Xenopus egg extracts; stable DNA-binding domain and coiled-coil domain of ATRIP are dispensable for Chk1 phosphorylation on defined checkpoint-inducing templates; ATRIP adopts an oligomeric state in egg extracts dependent on binding to ATR. Xenopus egg extract reconstitution, ATRIP mutant constructs, Chk1 phosphorylation assays The Journal of biological chemistry High 16186122
2005 The coiled-coil domain of ATRIP mediates ATRIP homodimerization/homo-oligomerization; this domain is essential for oligomerization, stable ATR binding, and accumulation of ATRIP at DNA lesions; replacing the coiled-coil with a heterologous dimerization domain restores stable ATR binding and localization, demonstrating that oligomerization per se (not the specific coiled-coil sequence) is required for ATR-dependent checkpoint signaling to Chk1. Co-immunoprecipitation, domain deletion/swap mutants, immunofluorescence, Chk1 phosphorylation assays The Journal of biological chemistry High 16027118
2005 The coiled-coil domain of ATRIP mediates self-dimerization in vivo and is required for stable translocation of the ATR-ATRIP complex to nuclear foci after genotoxic stress; dimerization-defective ATRIP compromises maintenance of replication forks during replication inhibitor treatment but does not impair the G2/M checkpoint after IR, revealing separable ATR-ATRIP functions. In vivo dimerization assays, immunofluorescence foci, DNA fiber assays, checkpoint assays Molecular biology of the cell Medium 16176973
2006 TopBP1 activates the ATR-ATRIP kinase complex; recombinant TopBP1 induces a large increase in ATR kinase activity in both Xenopus and human systems; the ATR-activating domain of TopBP1 is a conserved segment distinct from BRCT repeats; a point mutation inactivating this domain renders egg extracts defective in checkpoint regulation. In vitro kinase assays with recombinant TopBP1, Xenopus egg extract checkpoint assays, domain mapping, point mutagenesis Cell High 16530042
2006 ATRIP associates with RPA-ssDNA through multiple interactions: two major RPA-ssDNA-interacting domains flank the conserved coiled-coil domain; one internal region of ATRIP exhibits direct affinity for ssDNA; the N-terminus associates with RPA-ssDNA in two distinct ways, indicating dynamic and redundant interactions. Domain mapping, biochemical pulldown assays with RPA-ssDNA, ssDNA binding assays Proceedings of the National Academy of Sciences of the United States of America Medium 16407120
2007 A conserved checkpoint recruitment domain (CRD) at the N-terminus of ATRIP mediates the RPA interaction; mutations in the CRD of Saccharomyces cerevisiae Ddc2 disrupt Ddc2-RPA interaction, prevent proper localization to DNA breaks, sensitize yeast to DNA-damaging agents, and partially compromise checkpoint signaling; TopBP1-mediated ATR activation can occur independently of ATRIP-RPA interaction. Biochemical mapping, NMR, mutagenesis, yeast genetics, checkpoint assays, DNA damage sensitivity assays Molecular and cellular biology High 17339343
2007 CDK2-cyclin A phosphorylates ATRIP at S224 in vitro and in cells in a cell cycle-dependent manner; mutation of S224 to alanine causes a defect in ATR-ATRIP-dependent G2/M checkpoint maintenance after IR and UV radiation. Mass spectrometry phosphosite identification, in vitro kinase assay with CDK2-cyclin A, phospho-specific antibodies, CDK2 inhibitor treatment, checkpoint assays with S224A mutant Cancer research High 17638878
2008 ATRIP contains a TopBP1-interacting region required for TopBP1-ATR association and TopBP1-mediated ATR activation; ATR contains a PIKK Regulatory Domain (PRD) that is critical for activation by TopBP1 (mutations abolish activation without affecting basal kinase activity); both are required for checkpoint signaling and cellular viability after replication stress; the ATRIP TopBP1-interacting region is functionally conserved in yeast Ddc2. Domain mapping, site-directed mutagenesis, in vitro kinase assays, cellular complementation assays, yeast genetic epistasis Genes & development High 18519640
2012 ATRIP is crucial for DNA damage-induced FANCD2 monoubiquitination and FANCI phosphorylation; ATR phosphorylates recombinant FANCI in vitro, facilitated by FANCD2; the RPA-binding region of ATRIP (but not the TopBP1-binding region) is required for FANCD2 monoubiquitination, whereas Chk1 phosphorylation requires both domains. Conditional ATRIP-deficient DT40 cells, in vitro kinase assay with recombinant FANCI, domain deletion mutants, immunoblotting Cancer research High 22258451
2013 Nek1 kinase associates with ATR-ATRIP, maintains ATRIP protein levels, and promotes ATR-ATRIP association and basal ATR kinase activity even in undamaged cells; upon DNA damage, Nek1 is required for efficient phosphorylation of ATR substrates and ATR autophosphorylation at T1989; Nek1's promotion of ATR activation requires Nek1 kinase activity and its interaction with ATR-ATRIP. Co-immunoprecipitation, Nek1 siRNA knockdown, ATR kinase activity assays, ATR autophosphorylation assays, kinase-dead Nek1 mutant Proceedings of the National Academy of Sciences of the United States of America High 23345434
2013 The FA core complex enhances ATRIP binding and localization within damaged chromatin; in FA core complex-deficient cells, ATR-mediated phosphorylation of both ATRIP and FANCI is defective; canonical ATR activation via RAD17 and TOPBP1 is largely dispensable for FA pathway activation. Chromatin fractionation, conditional ATRIP-deficient DT40 cells, double mutant epistasis (RAD17/FANCD2), immunoblotting Nucleic acids research Medium 23723247
2013 The BRCA1 BRCT domains bind an ATRIP phosphopeptide (pS238-containing motif 235-PEACpSPQFG-243); crystal structures at 1.75 Å resolution reveal that pSer and Phe(+3) anchor the ATRIP peptide into the BRCT binding groove, with Gln(+2) accommodated through a conformational change of BRCA1 E1698. X-ray crystallography at 1.75 Å, isothermal titration calorimetry Biochemistry High 24073851
2014 ATRIP is SUMOylated by SUMO2/3 at K234 and K289; an ATRIP SUMOylation mutant fails to localize efficiently to DNA damage sites and support ATR activation; SUMOylation promotes simultaneous interaction with multiple ATRIP partners including ATR, RPA70, TopBP1, and the MRE11-RAD50-NBS1 complex, and these partners display affinity for SUMO2 chains in vitro; fusion of a SUMO2 chain to the ATRIP SUMOylation mutant partially rescues its defects. SUMO site identification, ATRIP SUMOylation mutants, co-immunoprecipitation, in vitro SUMO-binding assays, immunofluorescence, SUMO2-ATRIP fusion rescue Genes & development High 24990965
2016 SIRT2 deacetylates ATRIP at lysine K32 in response to replication stress; K32 deacetylation by SIRT2 promotes ATRIP accumulation at DNA damage sites, binding to RPA-ssDNA, ATR autophosphorylation, and ATR checkpoint signaling, as well as DNA replication fork progression and recovery. Co-immunoprecipitation, in vitro deacetylation assays, K32R/K32Q acetylation mutants, immunofluorescence foci, ATR autophosphorylation and Chk1 phosphorylation assays, DNA fiber assays Cell reports High 26854234
2017 Cryo-EM structure of the human ATR-ATRIP complex at 4.7 Å overall (3.9 Å for ATR C-terminal catalytic core) reveals a hollow 'heart'-shaped dimer of heterodimers; ATRIP contains 14 HEAT repeats in an extended 'S' shape; conformational flexibility of ATR allows ATRIP to lock the N-termini of two ATR monomers; catalytic pockets face outward without inhibitory occlusion. Cryo-electron microscopy, atomic model building Cell research High 29271416
2017 Cryo-EM structure of yeast Mec1-Ddc2 (ATR-ATRIP ortholog) at 3.9 Å reveals the complex forms a dimer of heterodimers through Mec1 PRD/FAT domains and the Ddc2 coiled-coil domain; the PRD inhibits the Mec1 activation loop, establishing an allosteric mechanism of kinase activation; PRD and Bridge domains constitute critical regulatory sites. Cryo-electron microscopy at 3.9 Å resolution Science High 29191911
2019 ZFP161 acts as a scaffolding protein that facilitates interaction between RPA and ATR/ATRIP; ZFP161 binds RPA and ATR/ATRIP through distinct regions and stabilizes the RPA-ATR-ATRIP complex at stalled replication forks, promoting ATR-Chk1 signaling. Co-immunoprecipitation, domain-specific binding assays, ZFP161 knockout mice, ATR/Chk1 signaling assays Nature communications Medium 31757956
2017 ATRIP directly interacts with MCM2, MCM3, MCM6, and MCM7; downregulation of MCM2 and MCM6 significantly reduces ATRIP chromatin loading; downregulation of MCM2 decreases ATRIP phosphorylation at S224 in a dose-dependent manner. Mass spectrometry, co-immunoprecipitation, GST pulldown, shRNA knockdown, chromatin fractionation Die Pharmazie Medium 29442041
2023 APE1 directly associates with ssDNA and recruits ATRIP onto ssDNA in an RPA-independent manner; the N-terminal motif of APE1 is required and sufficient for APE1-ATRIP interaction in vitro; this APE1-ATRIP interaction is required for ATRIP recruitment to ssDNA and ATR-Chk1 DDR pathway activation in Xenopus egg extracts; APE1 also directly associates with RPA70 and RPA32 via two distinct motifs. In vitro pulldown, Xenopus egg extract reconstitution, domain mapping with N-terminal APE1 motif mutants, Chk1 phosphorylation assays eLife Medium 37216274
2025 REV7 directly binds ATRIP through a defined REV7-interaction motif in ATRIP; mutation of this motif abrogates the REV7-ATRIP interaction in vitro and in cells; REV7 inhibits ATR-mediated phosphorylation of substrates including p53 in vitro; disruption of the REV7-ATRIP interaction enhances CHK1 phosphorylation at Ser317 in cells, establishing REV7 as a negative regulator of ATR signaling. In vitro binding assays, in vitro kinase assays, site-directed mutagenesis of REV7-interaction motif, cellular CHK1 phosphorylation assays Nucleic acids research High 41562258
2025 Cryo-EM structures of human ATR-ATRIP complex at ~3 Å overall resolution in the presence of ATR inhibitors VE-822 and RP-3500 reveal near-complete atomic model including subunit stoichiometry (dimer of heterodimers), intramolecular and intermolecular interactions, and PRD regulatory insertion; one ATR-ATRIP complex binds four VE-822 molecules (two in active site, two at ATR-ATR dimer interface); RP-3500 binding depends on two bound water molecules. Cryo-electron microscopy at ~3 Å resolution with two different inhibitor complexes Science bulletin High 40379520

Source papers

Stage 0 corpus · 50 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.) 2202 12791985
2001 ATR and ATRIP: partners in checkpoint signaling. Science (New York, N.Y.) 793 11721054
2006 TopBP1 activates the ATR-ATRIP complex. Cell 620 16530042
2008 TopBP1 activates ATR through ATRIP and a PIKK regulatory domain. Genes & development 296 18519640
2005 ATRIP binding to replication protein A-single-stranded DNA promotes ATR-ATRIP localization but is dispensable for Chk1 phosphorylation. Molecular biology of the cell 196 15743907
2004 Claspin and the activated form of ATR-ATRIP collaborate in the activation of Chk1. The Journal of biological chemistry 118 15371427
2007 Function of a conserved checkpoint recruitment domain in ATRIP proteins. Molecular and cellular biology 112 17339343
2012 Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel Syndrome. PLoS genetics 90 23144622
2006 ATRIP associates with replication protein A-coated ssDNA through multiple interactions. Proceedings of the National Academy of Sciences of the United States of America 89 16407120
2004 Quaternary structure of ATR and effects of ATRIP and replication protein A on its DNA binding and kinase activities. Molecular and cellular biology 83 14729973
2017 Cryo-EM structure of human ATR-ATRIP complex. Cell research 82 29271416
2005 ATRIP oligomerization is required for ATR-dependent checkpoint signaling. The Journal of biological chemistry 66 16027118
2008 How ATR turns on: TopBP1 goes on ATRIP with ATR. Genes & development 64 18519633
2013 Nek1 kinase associates with ATR-ATRIP and primes ATR for efficient DNA damage signaling. Proceedings of the National Academy of Sciences of the United States of America 63 23345434
2016 ATRIP Deacetylation by SIRT2 Drives ATR Checkpoint Activation by Promoting Binding to RPA-ssDNA. Cell reports 56 26854234
2014 SUMOylation of ATRIP potentiates DNA damage signaling by boosting multiple protein interactions in the ATR pathway. Genes & development 55 24990965
2007 Cyclin-dependent kinase 2 dependent phosphorylation of ATRIP regulates the G2-M checkpoint response to DNA damage. Cancer research 55 17638878
2017 3.9 Å structure of the yeast Mec1-Ddc2 complex, a homolog of human ATR-ATRIP. Science (New York, N.Y.) 54 29191911
2012 ATR-ATRIP kinase complex triggers activation of the Fanconi anemia DNA repair pathway. Cancer research 53 22258451
2005 Phosphorylation of Chk1 by ATM- and Rad3-related (ATR) in Xenopus egg extracts requires binding of ATRIP to ATR but not the stable DNA-binding or coiled-coil domains of ATRIP. The Journal of biological chemistry 51 16186122
2010 ATR and ATRIP are recruited to herpes simplex virus type 1 replication compartments even though ATR signaling is disabled. Journal of virology 49 20861269
2013 A novel interplay between the Fanconi anemia core complex and ATR-ATRIP kinase during DNA cross-link repair. Nucleic acids research 45 23723247
2004 A novel protein activity mediates DNA binding of an ATR-ATRIP complex. The Journal of biological chemistry 43 14724280
2011 The Ddc2/ATRIP checkpoint protein monitors meiotic recombination intermediates. Journal of cell science 40 21693576
2005 Dimerization of the ATRIP protein through the coiled-coil motif and its implication to the maintenance of stalled replication forks. Molecular biology of the cell 34 16176973
2014 Interaction between Rad9-Hus1-Rad1 and TopBP1 activates ATR-ATRIP and promotes TopBP1 recruitment to sites of UV-damage. DNA repair 33 25091155
2006 Recruitment of ATR-ATRIP, Rad17, and 9-1-1 complexes to DNA damage. Methods in enzymology 29 16793398
2006 Different requirements for the association of ATR-ATRIP and 9-1-1 to the stalled replication forks. Gene 26 16753272
2019 ZFP161 regulates replication fork stability and maintenance of genomic stability by recruiting the ATR/ATRIP complex. Nature communications 25 31757956
2019 Mec1ATR Autophosphorylation and Ddc2ATRIP Phosphorylation Regulates DNA Damage Checkpoint Signaling. Cell reports 20 31340146
2004 ATR-dependent phosphorylation of ATRIP in response to genotoxic stress. Biochemical and biophysical research communications 19 15451423
2004 Amino-terminal domain of ATRIP contributes to intranuclear relocation of the ATR-ATRIP complex following DNA damage. FEBS letters 19 15527801
2023 APE1 recruits ATRIP to ssDNA in an RPA-dependent and -independent manner to promote the ATR DNA damage response. eLife 17 37216274
2013 Structural basis for the BRCA1 BRCT interaction with the proteins ATRIP and BAAT1. Biochemistry 13 24073851
2010 A kinase-independent role for the Rad3(ATR)-Rad26(ATRIP) complex in recruitment of Tel1(ATM) to telomeres in fission yeast. PLoS genetics 12 20140190
2013 HIF1-regulated ATRIP expression is required for hypoxia induced ATR activation. FEBS letters 11 23454212
2023 A DNA damage-induced phosphorylation circuit enhances Mec1ATR Ddc2ATRIP recruitment to Replication Protein A. Proceedings of the National Academy of Sciences of the United States of America 10 36996117
2020 ATRIP protects progenitor cells against DNA damage in vivo. Cell death & disease 10 33110058
2023 Variants in ATRIP are associated with breast cancer susceptibility in the Polish population and UK Biobank. American journal of human genetics 9 36977412
2007 The Neurospora crassa UVS-3 epistasis group encodes homologues of the ATR/ATRIP checkpoint control system. DNA repair 6 17983847
2020 Progenitor death drives retinal dysplasia and neuronal degeneration in a mouse model of ATRIP-Seckel syndrome. Disease models & mechanisms 5 32994318
2017 The interaction between ATRIP and MCM complex is essential for ATRIP chromatin loading and its phosphorylation in mantle cell lymphoma cells. Die Pharmazie 4 29442041
2025 Replication stress, microcephalic primordial dwarfism, and compromised immunity in ATRIP deficient patients. The Journal of experimental medicine 3 40029331
2025 Molecular architecture and inhibition mechanism of human ATR-ATRIP. Science bulletin 3 40379520
2026 REV7 associates with ATRIP and inhibits ATR kinase activity. Nucleic acids research 1 41562258
2019 Preparation of endogenous TopBP1/Dpb11 and effect on central checkpoint kinase Mec1- Ddc2 (human ATR-ATRIP homolog). Biochemical and biophysical research communications 1 31349966
2015 Regulation of ATRIP protein abundance by RAD9 in the DNA damage repair pathway. Cellular and molecular biology (Noisy-le-Grand, France) 1 26667770
2026 Germline ATRIP variants and the risk of ovarian cancer. Genetics in medicine : official journal of the American College of Medical Genetics 0 42118082
2025 REV7 associates with ATRIP and inhibits ATR kinase activity. bioRxiv : the preprint server for biology 0 39868202
2025 A Novel ATRIP Mutation Detected in an Iranian Family with Familial Clustering of Breast Cancer: A Case Report. Current oncology (Toronto, Ont.) 0 41440239

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