{"gene":"ATMIN","run_date":"2026-06-09T22:02:44","timeline":{"discoveries":[{"year":2007,"finding":"ATMIN interacts with ATM through a C-terminal motif (also present in NBS1), is required for ATM signaling induced by chloroquine and hypotonic stress (but not ionizing radiation-induced DSBs), and ATMIN and ATM mutually stabilize each other's protein levels.","method":"Co-localization, co-immunoprecipitation, genetic deletion in primary murine fibroblasts, ATM substrate phosphorylation assays","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal protein stabilization, co-localization, substrate phosphorylation assays, multiple orthogonal methods in a single focused study, replicated in subsequent papers","pmids":["17525732"],"is_preprint":false},{"year":2007,"finding":"NBS1 and ATMIN compete for binding to ATM: IR-induced complex disruption between ATMIN and ATM was attenuated in cells with impaired NBS1 function, suggesting NBS1 displaces ATMIN from ATM after DSBs.","method":"Co-immunoprecipitation in NBS1-impaired and wild-type cells after ionizing radiation","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP with genetic perturbation, independently confirmed in subsequent studies (PMID:23219553, 25092319)","pmids":["17525732","23219553"],"is_preprint":false},{"year":2012,"finding":"NBS1 and ATMIN directly compete for ATM binding to control ATM signaling pathway choice: absence of ATMIN increases flux through the NBS1/IR pathway, and absence of NBS1 increases ATMIN-dependent ATM signaling; double deficiency completely abrogates ATM signaling and causes profound radiosensitivity.","method":"Genetic epistasis using atmin and nbs1 mutant mouse cells, ATM substrate phosphorylation assays, radiosensitivity assays","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic epistasis with double mutants, multiple cellular readouts, replicates and extends earlier Co-IP findings","pmids":["23219553"],"is_preprint":false},{"year":2014,"finding":"UBR5 (E3 ubiquitin ligase) interacts with ATMIN and ubiquitinates ATMIN at lysine 238 in an IR-stimulated manner; this ubiquitination decreases ATMIN's interaction with ATM and promotes MRN-mediated (NBS1-dependent) ATM signaling after DNA damage. Mutation of ATMIN K238 prevents ATMIN dissociation from ATM and inhibits NBS1 foci formation, checkpoint activation, and increases radiosensitivity.","method":"Co-immunoprecipitation, in vitro ubiquitination assay, site-directed mutagenesis (K238), focus formation assays, checkpoint activation assays","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro ubiquitination assay combined with mutagenesis and cellular functional assays, single lab but multiple orthogonal methods","pmids":["25092319"],"is_preprint":false},{"year":2015,"finding":"Monoubiquitinated PCNA (a marker of stalled replication forks) interacts with ATMIN via WRNIP1, and RAD18 (E3 ligase for PCNA monoubiquitination), WRNIP1, and ATMIN are specifically required for ATM signaling and 53BP1 focus formation induced by replication stress but not by ionizing radiation.","method":"Co-immunoprecipitation, siRNA/genetic knockdown, focus formation assays, ATM substrate phosphorylation assays","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP and genetic knockdown with defined cellular phenotype, single lab; contradicted by PMID:28648892","pmids":["26549024"],"is_preprint":false},{"year":2017,"finding":"NEGATIVE RESULT: ASCIZ/ATMIN is dispensable for ATM activation and phosphorylation of KAP1, p53, and H2AX in response to the replication-blocking agent aphidicolin, in both immortalized and primary ASCIZ/ATMIN-deficient MEFs and human ASCIZ/ATMIN-deleted lymphoma cells.","method":"ATM substrate phosphorylation assays in ASCIZ/ATMIN knockout MEFs and human deleted lymphoma cells treated with aphidicolin","journal":"DNA repair","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct genetic loss-of-function in multiple cell types with biochemical readouts; contradicts PMID:26549024 and PMID:25262557","pmids":["28648892"],"is_preprint":false},{"year":2005,"finding":"ASCIZ (ATMIN) forms nuclear foci in response to DNA methylating agents (but not DSB-inducing agents), acts as a lesion-specific scaffold that recruits Rad51 and promotes Rad51 focus formation in response to base methylation damage in an MLH1-dependent manner; ASCIZ depletion dramatically increases apoptosis after methylating DNA damage.","method":"siRNA knockdown, immunofluorescence focus formation assays, epistasis with MLH1, apoptosis assays","journal":"The EMBO journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined cellular phenotypes and epistasis, single lab","pmids":["15933716"],"is_preprint":false},{"year":2010,"finding":"ATMIN is required for ATM signaling in response to oxidative stress: atmin-null MEFs show reduced ATM phosphorylation and substrate phosphorylation after acute oxidative stress, accumulate DNA damage and prematurely senesce at atmospheric oxygen, and this defect is rescued by antioxidant or physiological oxygen. Conditional neural ATMIN deletion impairs aging-induced ATM signaling and causes accumulation of DNA damage in the aging cortex.","method":"Conditional and constitutive genetic knockout, ATM/substrate phosphorylation assays, senescence assays, antioxidant rescue, immunohistochemistry in aged brain","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple genetic models (constitutive and conditional KO), multiple readouts, antioxidant rescue experiment, in vivo and in vitro data","pmids":["20889973"],"is_preprint":false},{"year":2011,"finding":"ASCIZ (ATMIN) directly binds the Dynll1 promoter via its Zn2+ finger domain and transcriptionally activates DYNLL1 expression; DYNLL1 protein in turn binds to ten sites in the ASCIZ transcriptional activation domain and inhibits ASCIZ transcriptional activity, forming a negative feedback loop that auto-regulates DYNLL1 levels. DYNLL1 levels are reduced ~10-fold in ASCIZ-deficient human, mouse, and chicken cells.","method":"Chromatin immunoprecipitation (ChIP), luciferase reporter assays with zinc-finger domain mutants, co-immunoprecipitation, in vitro binding assays, genetic deletion across three species","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — ChIP, reporter assays with domain mutants, multi-species validation, multiple orthogonal methods","pmids":["22167198"],"is_preprint":false},{"year":2011,"finding":"DYNLL1 (LC8) binds to multiple SQ/TQ motifs in the C-terminal domain of ATMIN; co-expression of DYNLL1 and ATMIN mutually affects their intracellular localization, and DYNLL1 co-expression partly impedes DNA damage-induced ATMIN nuclear focus formation.","method":"Yeast two-hybrid, pepscan, gel filtration, NMR structure-based docking, live-cell fluorescence imaging of co-expressed fluorescent-tagged proteins","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — NMR structural modeling with in vitro binding and cellular imaging, single lab","pmids":["21971545"],"is_preprint":false},{"year":2011,"finding":"ATMIN deficiency in B cells impairs ATM signaling and results in defective peripheral V(D)J rearrangement and class switch recombination, leading to chromosomal translocations involving the Igh and Igl loci and B cell lymphoma development.","method":"B cell-conditional Atmin knockout mice, ATM substrate phosphorylation assays, chromosomal translocation analysis, lymphoma monitoring","journal":"Cancer cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo conditional genetic knockout with mechanistic pathway readouts and tumor phenotype, multiple orthogonal analyses","pmids":["21575860"],"is_preprint":false},{"year":2012,"finding":"ASCIZ regulates B cell development by activating DYNLL1 expression; ASCIZ-deficient B cell precursors have highly reduced DYNLL1 levels, the B cell lymphopenia in ASCIZ-deficient mice can be fully suppressed by deletion of the pro-apoptotic DYNLL1 target Bim, or rescued by ectopic DYNLL1 expression, placing ASCIZ upstream of DYNLL1 and Bim in B cell survival.","method":"Conditional knockout mice, ectopic DYNLL1 expression rescue, Bim genetic deletion epistasis, flow cytometry of B cell populations","journal":"The Journal of experimental medicine","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic epistasis with rescue experiments, ectopic expression rescue, multiple orthogonal genetic approaches","pmids":["22891272"],"is_preprint":false},{"year":2014,"finding":"ATMIN functions as a transcriptional regulator required for ciliogenesis primarily by controlling Dynll1 expression; depletion of ATMIN or DYNLL1 in cultured cells causes ciliary shortening and bulging similar to retrograde IFT mutants, and this is rescued by ectopic DYNLL1 or DYNLL2 expression. DYNLL1 and DYNLL2 localize to cilia in puncta consistent with IFT particles and physically interact with WDR34.","method":"Conditional mouse knockouts, siRNA depletion rescue with ectopic expression, immunofluorescence/confocal localization, co-immunoprecipitation (DYNLL1 with WDR34)","journal":"Development (Cambridge, England)","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic rescue experiment, Co-IP for protein interaction, in vivo and in vitro convergent evidence","pmids":["25294941"],"is_preprint":false},{"year":2014,"finding":"Atmin is required for normal kidney morphogenesis; Atmin mutant kidneys exhibit altered cytoskeletal organization and modulation of Wnt signaling pathway molecules including β-catenin, Daam2, and Vangl2, and genetic interaction between Atmin and Vangl2 was demonstrated by intercross experiments, placing ATMIN in the non-canonical Wnt/PCP pathway.","method":"Atmin mutant mouse model, genetic intercross epistasis (Atmin × Vangl2), immunostaining, transcriptional analysis","journal":"Human molecular genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis in vivo with pathway readouts, single lab","pmids":["24852369"],"is_preprint":false},{"year":2016,"finding":"ASCIZ (ATMIN) synergizes with MYC to transcriptionally activate DYNLL1 expression; deletion of Asciz or Dynll1 prevents abnormal pre-B cell expansion in pre-cancerous Eμ-Myc mice, potentiates MYC-induced apoptosis, and delays lymphoma development, establishing the ASCIZ-DYNLL1 axis as essential for survival of MYC-driven pre-neoplastic and malignant B cells.","method":"Conditional and constitutive genetic deletion in Eμ-Myc mouse lymphoma model, flow cytometry, apoptosis assays, survival analysis of tumor-bearing mice","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo genetic deletion in oncogene-driven model with multiple cellular phenotype readouts, inducible deletion in established lymphomas","pmids":["26832406"],"is_preprint":false},{"year":2018,"finding":"DYNLL1 promotes 53BP1 oligomerization and recruitment to DSB-associated chromatin, stimulated by its interaction with 53BP1. Deletion of Dynll1 or its transcriptional regulator Asciz, or mutation of DYNLL1 binding motifs in 53BP1, compromises class switch recombination and renders BRCA1-mutant cells and tumors resistant to PARP inhibitor treatment.","method":"Genetic deletion (Dynll1, Asciz), site-directed mutagenesis of DYNLL1 binding motifs in 53BP1, Co-IP/oligomerization assays, class switch recombination assays, in vivo PARP inhibitor treatment of BRCA1-mutant tumors","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple genetic deletions, mutagenesis of interaction motifs, in vivo tumor model, multiple orthogonal readouts","pmids":["30559443"],"is_preprint":false},{"year":2019,"finding":"PPARγ promotes UBR5 E3 ligase activity targeting ATMIN: PPARγ depletion increases ATMIN protein levels independent of transcription and suppresses DDR-induced ATM signaling; blocking ATMIN in this context restores ATM activation and DNA repair. In PAH patient PAECs, disrupted PPARγ-UBR5 interaction leads to heightened ATMIN expression and unresolved DNA damage.","method":"Proteomic/Co-IP interaction studies, siRNA knockdown, quantitative proteomics, ATM substrate phosphorylation assays, patient-derived cells","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP, knockdown rescue, patient cells, single lab with multiple approaches","pmids":["30699358"],"is_preprint":false},{"year":2021,"finding":"ASCIZ (ATMIN) and DYNLL1 are required for TLR4-, IL-1-, and CD40-mediated NF-κB pathway activation in B cells and fibroblasts (but not for antigen receptor or TNF-α signaling); DYNLL1 acts upstream of IκBα phosphorylation and degradation in this signal-specific pathway.","method":"B-cell-specific conditional knockout of Dynll1 and Asciz, NF-κB reporter assays, IκBα phosphorylation/degradation assays, in vivo antibody response assays","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic knockouts with defined pathway readouts, multiple stimuli tested, single lab","pmids":["34543116"],"is_preprint":false},{"year":2008,"finding":"ASCIZ deficiency in chicken DT40 B lymphocytes markedly increases Ig gene conversion rates, while ASCIZ overexpression reduces it below wild-type levels; ASCIZ loss suppresses the MMS hypersensitivity of polβ-deficient cells, indicating ASCIZ influences base repair pathway choice by reducing substrate availability for Ig gene conversion without directly controlling homologous recombination or abasic site formation.","method":"Gene targeting (knockout/overexpression) in chicken DT40 cells, Ig gene conversion assays, MMS sensitivity assays, epistasis with polβ deletion","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic manipulation in multiple backgrounds with epistasis, defined molecular readout, single lab","pmids":["18433721"],"is_preprint":false},{"year":2023,"finding":"Inter-motif linker length and specific motif sequences in the ASCIZ transcriptional activation domain control binding affinity and compositional heterogeneity of multivalent ASCIZ:DYNLL1 (LC8) complexes; short linkers between strong and weak motifs yield stable but potentially off-register duplexes, while long linkers produce heterogeneous complexes, and negative-stain EM shows two-mers dominate rather than expected three-mers.","method":"Isothermal titration calorimetry, analytical ultracentrifugation, native mass spectrometry, negative-stain electron microscopy, systematic motif deactivation mutagenesis","journal":"Biomolecules","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution with multiple biophysical methods and mutagenesis, single lab, Drosophila ASCIZ ortholog used","pmids":["36979339"],"is_preprint":false},{"year":2024,"finding":"USP10 deubiquitinase interacts with and stabilizes ATMIN protein; ATMIN transcriptionally activates LCK expression (confirmed by ChIP-seq), and the USP10-ATMIN-LCK axis promotes cell proliferation and docetaxel resistance in nasopharyngeal carcinoma.","method":"Mass spectrometry, Co-IP, ChIP-seq combined with RNA-seq, siRNA knockdown, overexpression, in vitro and in vivo proliferation/sensitivity assays","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP, ChIP-seq, functional rescue, single lab with multiple orthogonal methods","pmids":["38321024"],"is_preprint":false},{"year":2021,"finding":"ATMIN interacts with PARP1 (shown by co-immunoprecipitation) and acts on the Wnt signaling pathway via PARP1, influencing β-catenin/TCF4 binding affinity in MSI-high colorectal cancer; PARP1 inhibition decreases metastasis from ATMIN-knockdown cells.","method":"Co-immunoprecipitation, microarray/GSEA, PARP1 inhibitor treatment, in vivo metastasis model","journal":"Annals of surgical oncology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP plus pharmacological inhibitor, limited mechanistic depth, single lab","pmids":["34148137"],"is_preprint":false}],"current_model":"ATMIN (ASCIZ/ZNF822) is a dual-function protein that acts as an ATM cofactor by binding ATM through a C-terminal motif (competing with NBS1) to mediate non-DSB ATM signaling (oxidative stress, hypotonic stress, replication stress), and as a Zn2+-finger transcription factor that directly activates DYNLL1 expression; DYNLL1 in turn binds multiple sites in ATMIN's activation domain to form a negative feedback loop, and the ASCIZ-DYNLL1 axis organizes 53BP1 oligomeric complexes at DSBs to promote NHEJ/class switch recombination, regulates B cell survival via Bim, and modulates TLR4/IL-1-dependent NF-κB signaling; pathway selection between ATMIN- and NBS1-mediated ATM signaling is controlled by UBR5-mediated ubiquitination of ATMIN at K238, which dissociates ATMIN from ATM after ionizing radiation to allow MRN-dependent signaling."},"narrative":{"mechanistic_narrative":"ATMIN (ASCIZ/ZNF822) is a dual-function protein that operates both as an ATM cofactor for non-DSB damage signaling and as a zinc-finger transcription factor controlling DYNLL1 expression [PMID:17525732, PMID:22167198]. As an ATM partner, ATMIN binds ATM through a C-terminal motif and is required for ATM substrate phosphorylation in response to chloroquine, hypotonic stress, and oxidative stress, but not ionizing-radiation-induced DSBs; ATMIN and ATM reciprocally stabilize one another [PMID:17525732, PMID:20889973]. Pathway choice between ATMIN- and NBS1-mediated ATM signaling is governed by direct competition for ATM binding: loss of one partner increases flux through the other, and double deficiency abrogates ATM signaling and causes profound radiosensitivity [PMID:17525732, PMID:23219553]. After ionizing radiation, UBR5-mediated ubiquitination of ATMIN at K238 dissociates ATMIN from ATM to license MRN/NBS1-dependent signaling, and this is modulated upstream by PPARγ-promoted UBR5 activity [PMID:25092319, PMID:30699358]. Independently, ATMIN binds the Dynll1 promoter via its zinc-finger domain and transcriptionally activates DYNLL1, while DYNLL1 protein binds multiple SQ/TQ motifs in ATMIN's activation domain to inhibit its activity, forming an autoregulatory negative feedback loop [PMID:22167198, PMID:21971545]. Through this ASCIZ–DYNLL1 axis ATMIN drives DYNLL1-dependent 53BP1 oligomerization at DSBs to promote class switch recombination and PARP-inhibitor sensitivity of BRCA1-mutant tumors [PMID:30559443], supports B cell survival and development by suppressing the pro-apoptotic factor Bim and cooperating with MYC [PMID:22891272, PMID:26832406], sustains ciliogenesis [PMID:25294941], and enables TLR4/IL-1/CD40-dependent NF-κB activation [PMID:34543116].","teleology":[{"year":2005,"claim":"Before ATMIN was linked to ATM, this work established it as a lesion-specific nuclear scaffold, showing it responds to a defined subset of DNA damage rather than DSBs.","evidence":"siRNA knockdown, focus-formation immunofluorescence, MLH1 epistasis and apoptosis assays after methylating damage","pmids":["15933716"],"confidence":"Medium","gaps":["Molecular basis of methylation-lesion recognition undefined","Relationship to ATM signaling not yet established","Single lab, single readout class"]},{"year":2007,"claim":"Identified ATMIN as an ATM cofactor required for non-DSB ATM signaling and revealed NBS1 as a competing ATM partner, framing ATM activation as input-specific.","evidence":"Co-localization, reciprocal Co-IP, genetic deletion in murine fibroblasts and ATM substrate phosphorylation assays, including NBS1-impaired cells","pmids":["17525732","23219553"],"confidence":"High","gaps":["Mechanism by which different stresses route to ATMIN vs NBS1 unresolved","Structural basis of the shared C-terminal ATM-binding motif not defined"]},{"year":2008,"claim":"Demonstrated that ASCIZ influences base-repair pathway choice in B cells, separating its role from direct homologous recombination control.","evidence":"Gene targeting in chicken DT40 cells, Ig gene conversion and MMS-sensitivity assays, polβ epistasis","pmids":["18433721"],"confidence":"Medium","gaps":["Molecular mechanism linking ASCIZ to substrate availability unclear","Whether effect is transcriptional or scaffold-based not resolved"]},{"year":2010,"claim":"Established ATMIN as the conduit for ATM activation by oxidative stress, connecting it to DNA damage accumulation and senescence during aging.","evidence":"Constitutive and conditional KO mice, ATM/substrate phosphorylation, senescence and antioxidant-rescue assays, aged-brain immunohistochemistry","pmids":["20889973"],"confidence":"High","gaps":["How oxidative stress is sensed upstream of ATMIN unknown","Physiological aging phenotype mechanism beyond DNA damage accumulation incomplete"]},{"year":2011,"claim":"Defined ATMIN's second identity as a zinc-finger transcription factor and revealed the autoregulatory ASCIZ–DYNLL1 feedback loop linking it to its product.","evidence":"ChIP, luciferase reporters with zinc-finger mutants, Co-IP, in vitro binding and multi-species deletion; plus Y2H/pepscan/NMR docking and live-cell imaging","pmids":["22167198","21971545"],"confidence":"High","gaps":["Genome-wide target repertoire beyond DYNLL1 not mapped","How DYNLL1 binding mechanistically inhibits transcriptional activity not fully resolved"]},{"year":2011,"claim":"Connected ATMIN-dependent ATM signaling to adaptive immunity, showing it is required for V(D)J/class switch recombination and prevents lymphomagenic translocations.","evidence":"B cell-conditional Atmin knockout mice, ATM substrate phosphorylation, translocation analysis, lymphoma monitoring","pmids":["21575860"],"confidence":"High","gaps":["Whether immune defect is via ATM cofactor or DYNLL1 transcriptional arm not separated here","Translocation mechanism details incomplete"]},{"year":2012,"claim":"Resolved ATM pathway selection genetically and placed ATMIN upstream of DYNLL1/Bim in B cell survival.","evidence":"atmin/nbs1 double-mutant epistasis with radiosensitivity assays; conditional KO with DYNLL1 ectopic rescue and Bim deletion epistasis","pmids":["23219553","22891272"],"confidence":"High","gaps":["Switch determinant controlling ATMIN-vs-NBS1 flux still unknown","Direct DYNLL1 target genes beyond Bim regulation unmapped"]},{"year":2014,"claim":"Identified UBR5-mediated K238 ubiquitination as the molecular switch dissociating ATMIN from ATM after IR, and extended ATMIN's transcriptional function to ciliogenesis and Wnt/PCP signaling.","evidence":"Co-IP, in vitro ubiquitination, K238 mutagenesis, checkpoint/focus assays; conditional KO and rescue for cilia and Vangl2 genetic interaction for kidney/Wnt","pmids":["25092319","25294941","24852369"],"confidence":"High","gaps":["Signal triggering UBR5 recruitment to ATMIN after IR not defined","Whether ciliary and Wnt phenotypes are entirely DYNLL1-dependent unresolved"]},{"year":2016,"claim":"Showed the ASCIZ–DYNLL1 axis is co-opted by MYC and is essential for survival of MYC-driven pre-neoplastic and malignant B cells, establishing therapeutic relevance.","evidence":"Conditional/constitutive deletion in Eμ-Myc lymphoma model, flow cytometry, apoptosis and survival analysis","pmids":["26832406"],"confidence":"High","gaps":["Mechanism of ASCIZ-MYC synergy at the DYNLL1 promoter not detailed","Downstream effectors beyond DYNLL1 in this context not identified"]},{"year":2017,"claim":"Challenged the replication-stress ATM model by showing ASCIZ is dispensable for aphidicolin-induced ATM activation, leaving the role of ATMIN in replication-stress signaling unsettled.","evidence":"ATM substrate phosphorylation in ASCIZ-KO MEFs and human deleted lymphoma cells treated with aphidicolin","pmids":["28648892"],"confidence":"Medium","gaps":["Directly contradicts the WRNIP1/PCNA replication-stress findings","Different damaging agents and cell systems may explain discrepancy"]},{"year":2018,"claim":"Provided the mechanistic link from ASCIZ-driven DYNLL1 to DSB repair, showing DYNLL1 promotes 53BP1 oligomerization governing class switch recombination and PARP-inhibitor response.","evidence":"Dynll1/Asciz deletion, 53BP1 binding-motif mutagenesis, oligomerization/Co-IP and CSR assays, in vivo PARPi treatment of BRCA1-mutant tumors","pmids":["30559443"],"confidence":"High","gaps":["Whether ATMIN ATM-cofactor function contributes independently of DYNLL1 here unaddressed","Structural basis of 53BP1 oligomer assembly incomplete"]},{"year":2021,"claim":"Extended the ASCIZ–DYNLL1 axis to innate-type signaling, showing it is selectively required for TLR4/IL-1/CD40-dependent NF-κB activation.","evidence":"B-cell conditional Dynll1/Asciz KO, NF-κB reporters, IκBα phosphorylation/degradation assays, in vivo antibody responses","pmids":["34543116"],"confidence":"Medium","gaps":["Molecular target of DYNLL1 upstream of IκBα unidentified","Why signaling is receptor-selective unexplained"]},{"year":2024,"claim":"Identified USP10 as a deubiquitinase stabilizing ATMIN and uncovered LCK as a transcriptional target in cancer, broadening ATMIN's transcriptional output and oncogenic roles.","evidence":"Mass spectrometry, Co-IP, ChIP-seq/RNA-seq, knockdown/overexpression, in vitro and in vivo proliferation/drug-sensitivity assays","pmids":["38321024"],"confidence":"Medium","gaps":["Generality of LCK regulation beyond nasopharyngeal carcinoma unknown","Interplay between USP10 stabilization and UBR5 degradation not integrated"]},{"year":null,"claim":"How specific stress inputs are decoded to partition ATM signaling between ATMIN and NBS1, and the full genome-wide ATMIN transcriptional program beyond DYNLL1 and LCK, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of the ATM–ATMIN interface","Conflicting data on replication-stress role unreconciled","Determinants linking upstream lesion type to UBR5-dependent dissociation unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[8,12,20]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[8,20]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,2,7]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[6,8,9]}],"pathway":[{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[0,2,3]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[8,20]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[10,11,17]},{"term_id":"R-HSA-8953897","term_label":"Cellular responses to stimuli","supporting_discovery_ids":[7]}],"complexes":[],"partners":["ATM","NBS1","DYNLL1","UBR5","USP10","WRNIP1","PARP1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O43313","full_name":"ATM interactor","aliases":["ATM/ATR-substrate CHK2-interacting zinc finger protein","ASCIZ","Zinc finger protein 822"],"length_aa":823,"mass_kda":88.3,"function":"Transcription factor. Plays a crucial role in cell survival and RAD51 foci formation in response to methylating DNA damage. Involved in regulating the activity of ATM in the absence of DNA damage. May play a role in stabilizing ATM. Binds to the DYNLL1 promoter and activates its transcription","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/O43313/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ATMIN","classification":"Not Classified","n_dependent_lines":229,"n_total_lines":1208,"dependency_fraction":0.18956953642384106},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"DYNLL1","stoichiometry":0.2},{"gene":"DYNLL2","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/ATMIN","total_profiled":1310},"omim":[{"mim_id":"614693","title":"ATM INTERACTOR; ATMIN","url":"https://www.omim.org/entry/614693"},{"mim_id":"601562","title":"DYNEIN, LIGHT CHAIN, LC8 TYPE, 1; DYNLL1","url":"https://www.omim.org/entry/601562"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nuclear bodies","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/ATMIN"},"hgnc":{"alias_symbol":["ASCIZ","KIAA0431","ZNF822"],"prev_symbol":[]},"alphafold":{"accession":"O43313","domains":[{"cath_id":"-","chopping":"66-116_127-162","consensus_level":"medium","plddt":76.9555,"start":66,"end":162},{"cath_id":"-","chopping":"166-223","consensus_level":"medium","plddt":83.8269,"start":166,"end":223}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O43313","model_url":"https://alphafold.ebi.ac.uk/files/AF-O43313-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O43313-F1-predicted_aligned_error_v6.png","plddt_mean":47.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ATMIN","jax_strain_url":"https://www.jax.org/strain/search?query=ATMIN"},"sequence":{"accession":"O43313","fasta_url":"https://rest.uniprot.org/uniprotkb/O43313.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O43313/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O43313"}},"corpus_meta":[{"pmid":"30559443","id":"PMC_30559443","title":"The ASCIZ-DYNLL1 axis promotes 53BP1-dependent non-homologous end joining and PARP inhibitor sensitivity.","date":"2018","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/30559443","citation_count":87,"is_preprint":false},{"pmid":"17525732","id":"PMC_17525732","title":"ATMIN defines an NBS1-independent pathway of ATM signalling.","date":"2007","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/17525732","citation_count":72,"is_preprint":false},{"pmid":"30699358","id":"PMC_30699358","title":"PPARγ Interaction with UBR5/ATMIN Promotes DNA Repair to Maintain Endothelial Homeostasis.","date":"2019","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/30699358","citation_count":70,"is_preprint":false},{"pmid":"25092319","id":"PMC_25092319","title":"UBR5-mediated ubiquitination of ATMIN is required for ionizing radiation-induced ATM signaling and function.","date":"2014","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/25092319","citation_count":58,"is_preprint":false},{"pmid":"22167198","id":"PMC_22167198","title":"ATM substrate Chk2-interacting Zn2+ finger (ASCIZ) Is a bi-functional transcriptional activator and feedback sensor in the regulation of dynein light chain (DYNLL1) expression.","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22167198","citation_count":55,"is_preprint":false},{"pmid":"20889973","id":"PMC_20889973","title":"The ATM cofactor ATMIN protects against oxidative stress and accumulation of DNA damage in the aging brain.","date":"2010","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20889973","citation_count":52,"is_preprint":false},{"pmid":"15933716","id":"PMC_15933716","title":"ASCIZ regulates lesion-specific Rad51 focus formation and apoptosis after methylating DNA damage.","date":"2005","source":"The EMBO 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DYNLL1 and Bim.","date":"2012","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/22891272","citation_count":35,"is_preprint":false},{"pmid":"20975950","id":"PMC_20975950","title":"Dual functions of ASCIZ in the DNA base damage response and pulmonary organogenesis.","date":"2010","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/20975950","citation_count":33,"is_preprint":false},{"pmid":"21575860","id":"PMC_21575860","title":"ATMIN is required for maintenance of genomic stability and suppression of B cell lymphoma.","date":"2011","source":"Cancer cell","url":"https://pubmed.ncbi.nlm.nih.gov/21575860","citation_count":33,"is_preprint":false},{"pmid":"21971545","id":"PMC_21971545","title":"LC8 dynein light chain (DYNLL1) binds to the C-terminal domain of ATM-interacting protein (ATMIN/ASCIZ) and regulates its subcellular localization.","date":"2011","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/21971545","citation_count":31,"is_preprint":false},{"pmid":"27149854","id":"PMC_27149854","title":"A Comprehensive Analysis of the Dynamic Response to Aphidicolin-Mediated Replication Stress Uncovers Targets for ATM and ATMIN.","date":"2016","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/27149854","citation_count":29,"is_preprint":false},{"pmid":"26832406","id":"PMC_26832406","title":"The Transcription Factor ASCIZ and Its Target DYNLL1 Are Essential for the Development and Expansion of MYC-Driven B Cell Lymphoma.","date":"2016","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/26832406","citation_count":28,"is_preprint":false},{"pmid":"25262557","id":"PMC_25262557","title":"ATMIN is required for the ATM-mediated signaling and recruitment of 53BP1 to DNA damage sites upon replication stress.","date":"2014","source":"DNA repair","url":"https://pubmed.ncbi.nlm.nih.gov/25262557","citation_count":28,"is_preprint":false},{"pmid":"19001856","id":"PMC_19001856","title":"ATMINistrating ATM signalling: regulation of ATM by ATMIN.","date":"2008","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/19001856","citation_count":27,"is_preprint":false},{"pmid":"30414501","id":"PMC_30414501","title":"Atmin modulates Pkhd1 expression and may mediate Autosomal Recessive Polycystic Kidney Disease (ARPKD) through altered non-canonical Wnt/Planar Cell Polarity (PCP) signalling.","date":"2018","source":"Biochimica et biophysica acta. Molecular basis of disease","url":"https://pubmed.ncbi.nlm.nih.gov/30414501","citation_count":20,"is_preprint":false},{"pmid":"26984279","id":"PMC_26984279","title":"Inactivation of the ATMIN/ATM pathway protects against glioblastoma formation.","date":"2016","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/26984279","citation_count":18,"is_preprint":false},{"pmid":"26875667","id":"PMC_26875667","title":"Mechanisms and consequences of ATMIN repression in hypoxic conditions: roles for p53 and HIF-1.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/26875667","citation_count":16,"is_preprint":false},{"pmid":"18433721","id":"PMC_18433721","title":"DNA damage response protein ASCIZ links base excision repair with immunoglobulin gene conversion.","date":"2008","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/18433721","citation_count":13,"is_preprint":false},{"pmid":"24852369","id":"PMC_24852369","title":"Atmin mediates kidney morphogenesis by modulating Wnt signaling.","date":"2014","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/24852369","citation_count":13,"is_preprint":false},{"pmid":"26544571","id":"PMC_26544571","title":"DNA Repair Cofactors ATMIN and NBS1 Are Required to Suppress T Cell Activation.","date":"2015","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/26544571","citation_count":12,"is_preprint":false},{"pmid":"31481498","id":"PMC_31481498","title":"ATMIN Is a Tumor Suppressor Gene in Lung Adenocarcinoma.","date":"2019","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/31481498","citation_count":12,"is_preprint":false},{"pmid":"34273621","id":"PMC_34273621","title":"Involvement of ATMIN-DYNLL1-MRN axis in the progression and aggressiveness of serous ovarian cancer.","date":"2021","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/34273621","citation_count":10,"is_preprint":false},{"pmid":"18728389","id":"PMC_18728389","title":"Mdt1/ASCIZ: a new DNA damage response protein family.","date":"2008","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/18728389","citation_count":9,"is_preprint":false},{"pmid":"36979339","id":"PMC_36979339","title":"Linker Length Drives Heterogeneity of Multivalent Complexes of Hub Protein LC8 and Transcription Factor ASCIZ.","date":"2023","source":"Biomolecules","url":"https://pubmed.ncbi.nlm.nih.gov/36979339","citation_count":9,"is_preprint":false},{"pmid":"28648892","id":"PMC_28648892","title":"ASCIZ/ATMIN is dispensable for ATM signaling in response to replication stress.","date":"2017","source":"DNA repair","url":"https://pubmed.ncbi.nlm.nih.gov/28648892","citation_count":9,"is_preprint":false},{"pmid":"21415597","id":"PMC_21415597","title":"A breathtaking phenotype: unexpected roles of the DNA base damage response protein ASCIZ as a key regulator of early lung development.","date":"2011","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/21415597","citation_count":9,"is_preprint":false},{"pmid":"36626032","id":"PMC_36626032","title":"CircMAN1A2 contributes to nasopharyngeal carcinoma progression via enhancing the ubiquitination of ATMIN through miR-135a-3p/UBR5 axis.","date":"2023","source":"Human cell","url":"https://pubmed.ncbi.nlm.nih.gov/36626032","citation_count":8,"is_preprint":false},{"pmid":"34148137","id":"PMC_34148137","title":"ATMIN Suppresses Metastasis by Altering the WNT-Signaling Pathway via PARP1 in MSI-High Colorectal Cancer.","date":"2021","source":"Annals of surgical 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ATMIN in polycystic kidney disease.","date":"2016","source":"Biochemical Society transactions","url":"https://pubmed.ncbi.nlm.nih.gov/27913685","citation_count":5,"is_preprint":false},{"pmid":"36119811","id":"PMC_36119811","title":"ATMIN enhances invasion by altering PARP1 in MSS colorectal cancer.","date":"2022","source":"American journal of cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/36119811","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":18443,"output_tokens":5569,"usd":0.069432,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":14399,"output_tokens":4514,"usd":0.092423,"stage2_stop_reason":"end_turn"},"total_usd":0.161855,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"ATMIN interacts with ATM through a C-terminal motif (also present in NBS1), is required for ATM signaling induced by chloroquine and hypotonic stress (but not ionizing radiation-induced DSBs), and ATMIN and ATM mutually stabilize each other's protein levels.\",\n      \"method\": \"Co-localization, co-immunoprecipitation, genetic deletion in primary murine fibroblasts, ATM substrate phosphorylation assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal protein stabilization, co-localization, substrate phosphorylation assays, multiple orthogonal methods in a single focused study, replicated in subsequent papers\",\n      \"pmids\": [\"17525732\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"NBS1 and ATMIN compete for binding to ATM: IR-induced complex disruption between ATMIN and ATM was attenuated in cells with impaired NBS1 function, suggesting NBS1 displaces ATMIN from ATM after DSBs.\",\n      \"method\": \"Co-immunoprecipitation in NBS1-impaired and wild-type cells after ionizing radiation\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP with genetic perturbation, independently confirmed in subsequent studies (PMID:23219553, 25092319)\",\n      \"pmids\": [\"17525732\", \"23219553\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"NBS1 and ATMIN directly compete for ATM binding to control ATM signaling pathway choice: absence of ATMIN increases flux through the NBS1/IR pathway, and absence of NBS1 increases ATMIN-dependent ATM signaling; double deficiency completely abrogates ATM signaling and causes profound radiosensitivity.\",\n      \"method\": \"Genetic epistasis using atmin and nbs1 mutant mouse cells, ATM substrate phosphorylation assays, radiosensitivity assays\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic epistasis with double mutants, multiple cellular readouts, replicates and extends earlier Co-IP findings\",\n      \"pmids\": [\"23219553\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"UBR5 (E3 ubiquitin ligase) interacts with ATMIN and ubiquitinates ATMIN at lysine 238 in an IR-stimulated manner; this ubiquitination decreases ATMIN's interaction with ATM and promotes MRN-mediated (NBS1-dependent) ATM signaling after DNA damage. Mutation of ATMIN K238 prevents ATMIN dissociation from ATM and inhibits NBS1 foci formation, checkpoint activation, and increases radiosensitivity.\",\n      \"method\": \"Co-immunoprecipitation, in vitro ubiquitination assay, site-directed mutagenesis (K238), focus formation assays, checkpoint activation assays\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro ubiquitination assay combined with mutagenesis and cellular functional assays, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"25092319\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Monoubiquitinated PCNA (a marker of stalled replication forks) interacts with ATMIN via WRNIP1, and RAD18 (E3 ligase for PCNA monoubiquitination), WRNIP1, and ATMIN are specifically required for ATM signaling and 53BP1 focus formation induced by replication stress but not by ionizing radiation.\",\n      \"method\": \"Co-immunoprecipitation, siRNA/genetic knockdown, focus formation assays, ATM substrate phosphorylation assays\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP and genetic knockdown with defined cellular phenotype, single lab; contradicted by PMID:28648892\",\n      \"pmids\": [\"26549024\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"NEGATIVE RESULT: ASCIZ/ATMIN is dispensable for ATM activation and phosphorylation of KAP1, p53, and H2AX in response to the replication-blocking agent aphidicolin, in both immortalized and primary ASCIZ/ATMIN-deficient MEFs and human ASCIZ/ATMIN-deleted lymphoma cells.\",\n      \"method\": \"ATM substrate phosphorylation assays in ASCIZ/ATMIN knockout MEFs and human deleted lymphoma cells treated with aphidicolin\",\n      \"journal\": \"DNA repair\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct genetic loss-of-function in multiple cell types with biochemical readouts; contradicts PMID:26549024 and PMID:25262557\",\n      \"pmids\": [\"28648892\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"ASCIZ (ATMIN) forms nuclear foci in response to DNA methylating agents (but not DSB-inducing agents), acts as a lesion-specific scaffold that recruits Rad51 and promotes Rad51 focus formation in response to base methylation damage in an MLH1-dependent manner; ASCIZ depletion dramatically increases apoptosis after methylating DNA damage.\",\n      \"method\": \"siRNA knockdown, immunofluorescence focus formation assays, epistasis with MLH1, apoptosis assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined cellular phenotypes and epistasis, single lab\",\n      \"pmids\": [\"15933716\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"ATMIN is required for ATM signaling in response to oxidative stress: atmin-null MEFs show reduced ATM phosphorylation and substrate phosphorylation after acute oxidative stress, accumulate DNA damage and prematurely senesce at atmospheric oxygen, and this defect is rescued by antioxidant or physiological oxygen. Conditional neural ATMIN deletion impairs aging-induced ATM signaling and causes accumulation of DNA damage in the aging cortex.\",\n      \"method\": \"Conditional and constitutive genetic knockout, ATM/substrate phosphorylation assays, senescence assays, antioxidant rescue, immunohistochemistry in aged brain\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple genetic models (constitutive and conditional KO), multiple readouts, antioxidant rescue experiment, in vivo and in vitro data\",\n      \"pmids\": [\"20889973\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"ASCIZ (ATMIN) directly binds the Dynll1 promoter via its Zn2+ finger domain and transcriptionally activates DYNLL1 expression; DYNLL1 protein in turn binds to ten sites in the ASCIZ transcriptional activation domain and inhibits ASCIZ transcriptional activity, forming a negative feedback loop that auto-regulates DYNLL1 levels. DYNLL1 levels are reduced ~10-fold in ASCIZ-deficient human, mouse, and chicken cells.\",\n      \"method\": \"Chromatin immunoprecipitation (ChIP), luciferase reporter assays with zinc-finger domain mutants, co-immunoprecipitation, in vitro binding assays, genetic deletion across three species\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — ChIP, reporter assays with domain mutants, multi-species validation, multiple orthogonal methods\",\n      \"pmids\": [\"22167198\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"DYNLL1 (LC8) binds to multiple SQ/TQ motifs in the C-terminal domain of ATMIN; co-expression of DYNLL1 and ATMIN mutually affects their intracellular localization, and DYNLL1 co-expression partly impedes DNA damage-induced ATMIN nuclear focus formation.\",\n      \"method\": \"Yeast two-hybrid, pepscan, gel filtration, NMR structure-based docking, live-cell fluorescence imaging of co-expressed fluorescent-tagged proteins\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — NMR structural modeling with in vitro binding and cellular imaging, single lab\",\n      \"pmids\": [\"21971545\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"ATMIN deficiency in B cells impairs ATM signaling and results in defective peripheral V(D)J rearrangement and class switch recombination, leading to chromosomal translocations involving the Igh and Igl loci and B cell lymphoma development.\",\n      \"method\": \"B cell-conditional Atmin knockout mice, ATM substrate phosphorylation assays, chromosomal translocation analysis, lymphoma monitoring\",\n      \"journal\": \"Cancer cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo conditional genetic knockout with mechanistic pathway readouts and tumor phenotype, multiple orthogonal analyses\",\n      \"pmids\": [\"21575860\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"ASCIZ regulates B cell development by activating DYNLL1 expression; ASCIZ-deficient B cell precursors have highly reduced DYNLL1 levels, the B cell lymphopenia in ASCIZ-deficient mice can be fully suppressed by deletion of the pro-apoptotic DYNLL1 target Bim, or rescued by ectopic DYNLL1 expression, placing ASCIZ upstream of DYNLL1 and Bim in B cell survival.\",\n      \"method\": \"Conditional knockout mice, ectopic DYNLL1 expression rescue, Bim genetic deletion epistasis, flow cytometry of B cell populations\",\n      \"journal\": \"The Journal of experimental medicine\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic epistasis with rescue experiments, ectopic expression rescue, multiple orthogonal genetic approaches\",\n      \"pmids\": [\"22891272\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"ATMIN functions as a transcriptional regulator required for ciliogenesis primarily by controlling Dynll1 expression; depletion of ATMIN or DYNLL1 in cultured cells causes ciliary shortening and bulging similar to retrograde IFT mutants, and this is rescued by ectopic DYNLL1 or DYNLL2 expression. DYNLL1 and DYNLL2 localize to cilia in puncta consistent with IFT particles and physically interact with WDR34.\",\n      \"method\": \"Conditional mouse knockouts, siRNA depletion rescue with ectopic expression, immunofluorescence/confocal localization, co-immunoprecipitation (DYNLL1 with WDR34)\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic rescue experiment, Co-IP for protein interaction, in vivo and in vitro convergent evidence\",\n      \"pmids\": [\"25294941\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Atmin is required for normal kidney morphogenesis; Atmin mutant kidneys exhibit altered cytoskeletal organization and modulation of Wnt signaling pathway molecules including β-catenin, Daam2, and Vangl2, and genetic interaction between Atmin and Vangl2 was demonstrated by intercross experiments, placing ATMIN in the non-canonical Wnt/PCP pathway.\",\n      \"method\": \"Atmin mutant mouse model, genetic intercross epistasis (Atmin × Vangl2), immunostaining, transcriptional analysis\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis in vivo with pathway readouts, single lab\",\n      \"pmids\": [\"24852369\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"ASCIZ (ATMIN) synergizes with MYC to transcriptionally activate DYNLL1 expression; deletion of Asciz or Dynll1 prevents abnormal pre-B cell expansion in pre-cancerous Eμ-Myc mice, potentiates MYC-induced apoptosis, and delays lymphoma development, establishing the ASCIZ-DYNLL1 axis as essential for survival of MYC-driven pre-neoplastic and malignant B cells.\",\n      \"method\": \"Conditional and constitutive genetic deletion in Eμ-Myc mouse lymphoma model, flow cytometry, apoptosis assays, survival analysis of tumor-bearing mice\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo genetic deletion in oncogene-driven model with multiple cellular phenotype readouts, inducible deletion in established lymphomas\",\n      \"pmids\": [\"26832406\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"DYNLL1 promotes 53BP1 oligomerization and recruitment to DSB-associated chromatin, stimulated by its interaction with 53BP1. Deletion of Dynll1 or its transcriptional regulator Asciz, or mutation of DYNLL1 binding motifs in 53BP1, compromises class switch recombination and renders BRCA1-mutant cells and tumors resistant to PARP inhibitor treatment.\",\n      \"method\": \"Genetic deletion (Dynll1, Asciz), site-directed mutagenesis of DYNLL1 binding motifs in 53BP1, Co-IP/oligomerization assays, class switch recombination assays, in vivo PARP inhibitor treatment of BRCA1-mutant tumors\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple genetic deletions, mutagenesis of interaction motifs, in vivo tumor model, multiple orthogonal readouts\",\n      \"pmids\": [\"30559443\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"PPARγ promotes UBR5 E3 ligase activity targeting ATMIN: PPARγ depletion increases ATMIN protein levels independent of transcription and suppresses DDR-induced ATM signaling; blocking ATMIN in this context restores ATM activation and DNA repair. In PAH patient PAECs, disrupted PPARγ-UBR5 interaction leads to heightened ATMIN expression and unresolved DNA damage.\",\n      \"method\": \"Proteomic/Co-IP interaction studies, siRNA knockdown, quantitative proteomics, ATM substrate phosphorylation assays, patient-derived cells\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, knockdown rescue, patient cells, single lab with multiple approaches\",\n      \"pmids\": [\"30699358\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"ASCIZ (ATMIN) and DYNLL1 are required for TLR4-, IL-1-, and CD40-mediated NF-κB pathway activation in B cells and fibroblasts (but not for antigen receptor or TNF-α signaling); DYNLL1 acts upstream of IκBα phosphorylation and degradation in this signal-specific pathway.\",\n      \"method\": \"B-cell-specific conditional knockout of Dynll1 and Asciz, NF-κB reporter assays, IκBα phosphorylation/degradation assays, in vivo antibody response assays\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic knockouts with defined pathway readouts, multiple stimuli tested, single lab\",\n      \"pmids\": [\"34543116\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"ASCIZ deficiency in chicken DT40 B lymphocytes markedly increases Ig gene conversion rates, while ASCIZ overexpression reduces it below wild-type levels; ASCIZ loss suppresses the MMS hypersensitivity of polβ-deficient cells, indicating ASCIZ influences base repair pathway choice by reducing substrate availability for Ig gene conversion without directly controlling homologous recombination or abasic site formation.\",\n      \"method\": \"Gene targeting (knockout/overexpression) in chicken DT40 cells, Ig gene conversion assays, MMS sensitivity assays, epistasis with polβ deletion\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic manipulation in multiple backgrounds with epistasis, defined molecular readout, single lab\",\n      \"pmids\": [\"18433721\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Inter-motif linker length and specific motif sequences in the ASCIZ transcriptional activation domain control binding affinity and compositional heterogeneity of multivalent ASCIZ:DYNLL1 (LC8) complexes; short linkers between strong and weak motifs yield stable but potentially off-register duplexes, while long linkers produce heterogeneous complexes, and negative-stain EM shows two-mers dominate rather than expected three-mers.\",\n      \"method\": \"Isothermal titration calorimetry, analytical ultracentrifugation, native mass spectrometry, negative-stain electron microscopy, systematic motif deactivation mutagenesis\",\n      \"journal\": \"Biomolecules\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution with multiple biophysical methods and mutagenesis, single lab, Drosophila ASCIZ ortholog used\",\n      \"pmids\": [\"36979339\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"USP10 deubiquitinase interacts with and stabilizes ATMIN protein; ATMIN transcriptionally activates LCK expression (confirmed by ChIP-seq), and the USP10-ATMIN-LCK axis promotes cell proliferation and docetaxel resistance in nasopharyngeal carcinoma.\",\n      \"method\": \"Mass spectrometry, Co-IP, ChIP-seq combined with RNA-seq, siRNA knockdown, overexpression, in vitro and in vivo proliferation/sensitivity assays\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, ChIP-seq, functional rescue, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"38321024\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"ATMIN interacts with PARP1 (shown by co-immunoprecipitation) and acts on the Wnt signaling pathway via PARP1, influencing β-catenin/TCF4 binding affinity in MSI-high colorectal cancer; PARP1 inhibition decreases metastasis from ATMIN-knockdown cells.\",\n      \"method\": \"Co-immunoprecipitation, microarray/GSEA, PARP1 inhibitor treatment, in vivo metastasis model\",\n      \"journal\": \"Annals of surgical oncology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP plus pharmacological inhibitor, limited mechanistic depth, single lab\",\n      \"pmids\": [\"34148137\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ATMIN (ASCIZ/ZNF822) is a dual-function protein that acts as an ATM cofactor by binding ATM through a C-terminal motif (competing with NBS1) to mediate non-DSB ATM signaling (oxidative stress, hypotonic stress, replication stress), and as a Zn2+-finger transcription factor that directly activates DYNLL1 expression; DYNLL1 in turn binds multiple sites in ATMIN's activation domain to form a negative feedback loop, and the ASCIZ-DYNLL1 axis organizes 53BP1 oligomeric complexes at DSBs to promote NHEJ/class switch recombination, regulates B cell survival via Bim, and modulates TLR4/IL-1-dependent NF-κB signaling; pathway selection between ATMIN- and NBS1-mediated ATM signaling is controlled by UBR5-mediated ubiquitination of ATMIN at K238, which dissociates ATMIN from ATM after ionizing radiation to allow MRN-dependent signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ATMIN (ASCIZ/ZNF822) is a dual-function protein that operates both as an ATM cofactor for non-DSB damage signaling and as a zinc-finger transcription factor controlling DYNLL1 expression [#0, #8]. As an ATM partner, ATMIN binds ATM through a C-terminal motif and is required for ATM substrate phosphorylation in response to chloroquine, hypotonic stress, and oxidative stress, but not ionizing-radiation-induced DSBs; ATMIN and ATM reciprocally stabilize one another [#0, #7]. Pathway choice between ATMIN- and NBS1-mediated ATM signaling is governed by direct competition for ATM binding: loss of one partner increases flux through the other, and double deficiency abrogates ATM signaling and causes profound radiosensitivity [#1, #2]. After ionizing radiation, UBR5-mediated ubiquitination of ATMIN at K238 dissociates ATMIN from ATM to license MRN/NBS1-dependent signaling, and this is modulated upstream by PPARγ-promoted UBR5 activity [#3, #16]. Independently, ATMIN binds the Dynll1 promoter via its zinc-finger domain and transcriptionally activates DYNLL1, while DYNLL1 protein binds multiple SQ/TQ motifs in ATMIN's activation domain to inhibit its activity, forming an autoregulatory negative feedback loop [#8, #9]. Through this ASCIZ–DYNLL1 axis ATMIN drives DYNLL1-dependent 53BP1 oligomerization at DSBs to promote class switch recombination and PARP-inhibitor sensitivity of BRCA1-mutant tumors [#15], supports B cell survival and development by suppressing the pro-apoptotic factor Bim and cooperating with MYC [#11, #14], sustains ciliogenesis [#12], and enables TLR4/IL-1/CD40-dependent NF-κB activation [#17].\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Before ATMIN was linked to ATM, this work established it as a lesion-specific nuclear scaffold, showing it responds to a defined subset of DNA damage rather than DSBs.\",\n      \"evidence\": \"siRNA knockdown, focus-formation immunofluorescence, MLH1 epistasis and apoptosis assays after methylating damage\",\n      \"pmids\": [\"15933716\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular basis of methylation-lesion recognition undefined\", \"Relationship to ATM signaling not yet established\", \"Single lab, single readout class\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Identified ATMIN as an ATM cofactor required for non-DSB ATM signaling and revealed NBS1 as a competing ATM partner, framing ATM activation as input-specific.\",\n      \"evidence\": \"Co-localization, reciprocal Co-IP, genetic deletion in murine fibroblasts and ATM substrate phosphorylation assays, including NBS1-impaired cells\",\n      \"pmids\": [\"17525732\", \"23219553\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which different stresses route to ATMIN vs NBS1 unresolved\", \"Structural basis of the shared C-terminal ATM-binding motif not defined\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Demonstrated that ASCIZ influences base-repair pathway choice in B cells, separating its role from direct homologous recombination control.\",\n      \"evidence\": \"Gene targeting in chicken DT40 cells, Ig gene conversion and MMS-sensitivity assays, polβ epistasis\",\n      \"pmids\": [\"18433721\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism linking ASCIZ to substrate availability unclear\", \"Whether effect is transcriptional or scaffold-based not resolved\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Established ATMIN as the conduit for ATM activation by oxidative stress, connecting it to DNA damage accumulation and senescence during aging.\",\n      \"evidence\": \"Constitutive and conditional KO mice, ATM/substrate phosphorylation, senescence and antioxidant-rescue assays, aged-brain immunohistochemistry\",\n      \"pmids\": [\"20889973\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How oxidative stress is sensed upstream of ATMIN unknown\", \"Physiological aging phenotype mechanism beyond DNA damage accumulation incomplete\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Defined ATMIN's second identity as a zinc-finger transcription factor and revealed the autoregulatory ASCIZ–DYNLL1 feedback loop linking it to its product.\",\n      \"evidence\": \"ChIP, luciferase reporters with zinc-finger mutants, Co-IP, in vitro binding and multi-species deletion; plus Y2H/pepscan/NMR docking and live-cell imaging\",\n      \"pmids\": [\"22167198\", \"21971545\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Genome-wide target repertoire beyond DYNLL1 not mapped\", \"How DYNLL1 binding mechanistically inhibits transcriptional activity not fully resolved\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Connected ATMIN-dependent ATM signaling to adaptive immunity, showing it is required for V(D)J/class switch recombination and prevents lymphomagenic translocations.\",\n      \"evidence\": \"B cell-conditional Atmin knockout mice, ATM substrate phosphorylation, translocation analysis, lymphoma monitoring\",\n      \"pmids\": [\"21575860\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether immune defect is via ATM cofactor or DYNLL1 transcriptional arm not separated here\", \"Translocation mechanism details incomplete\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Resolved ATM pathway selection genetically and placed ATMIN upstream of DYNLL1/Bim in B cell survival.\",\n      \"evidence\": \"atmin/nbs1 double-mutant epistasis with radiosensitivity assays; conditional KO with DYNLL1 ectopic rescue and Bim deletion epistasis\",\n      \"pmids\": [\"23219553\", \"22891272\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Switch determinant controlling ATMIN-vs-NBS1 flux still unknown\", \"Direct DYNLL1 target genes beyond Bim regulation unmapped\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identified UBR5-mediated K238 ubiquitination as the molecular switch dissociating ATMIN from ATM after IR, and extended ATMIN's transcriptional function to ciliogenesis and Wnt/PCP signaling.\",\n      \"evidence\": \"Co-IP, in vitro ubiquitination, K238 mutagenesis, checkpoint/focus assays; conditional KO and rescue for cilia and Vangl2 genetic interaction for kidney/Wnt\",\n      \"pmids\": [\"25092319\", \"25294941\", \"24852369\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Signal triggering UBR5 recruitment to ATMIN after IR not defined\", \"Whether ciliary and Wnt phenotypes are entirely DYNLL1-dependent unresolved\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Showed the ASCIZ–DYNLL1 axis is co-opted by MYC and is essential for survival of MYC-driven pre-neoplastic and malignant B cells, establishing therapeutic relevance.\",\n      \"evidence\": \"Conditional/constitutive deletion in Eμ-Myc lymphoma model, flow cytometry, apoptosis and survival analysis\",\n      \"pmids\": [\"26832406\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of ASCIZ-MYC synergy at the DYNLL1 promoter not detailed\", \"Downstream effectors beyond DYNLL1 in this context not identified\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Challenged the replication-stress ATM model by showing ASCIZ is dispensable for aphidicolin-induced ATM activation, leaving the role of ATMIN in replication-stress signaling unsettled.\",\n      \"evidence\": \"ATM substrate phosphorylation in ASCIZ-KO MEFs and human deleted lymphoma cells treated with aphidicolin\",\n      \"pmids\": [\"28648892\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Directly contradicts the WRNIP1/PCNA replication-stress findings\", \"Different damaging agents and cell systems may explain discrepancy\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Provided the mechanistic link from ASCIZ-driven DYNLL1 to DSB repair, showing DYNLL1 promotes 53BP1 oligomerization governing class switch recombination and PARP-inhibitor response.\",\n      \"evidence\": \"Dynll1/Asciz deletion, 53BP1 binding-motif mutagenesis, oligomerization/Co-IP and CSR assays, in vivo PARPi treatment of BRCA1-mutant tumors\",\n      \"pmids\": [\"30559443\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether ATMIN ATM-cofactor function contributes independently of DYNLL1 here unaddressed\", \"Structural basis of 53BP1 oligomer assembly incomplete\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Extended the ASCIZ–DYNLL1 axis to innate-type signaling, showing it is selectively required for TLR4/IL-1/CD40-dependent NF-κB activation.\",\n      \"evidence\": \"B-cell conditional Dynll1/Asciz KO, NF-κB reporters, IκBα phosphorylation/degradation assays, in vivo antibody responses\",\n      \"pmids\": [\"34543116\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular target of DYNLL1 upstream of IκBα unidentified\", \"Why signaling is receptor-selective unexplained\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identified USP10 as a deubiquitinase stabilizing ATMIN and uncovered LCK as a transcriptional target in cancer, broadening ATMIN's transcriptional output and oncogenic roles.\",\n      \"evidence\": \"Mass spectrometry, Co-IP, ChIP-seq/RNA-seq, knockdown/overexpression, in vitro and in vivo proliferation/drug-sensitivity assays\",\n      \"pmids\": [\"38321024\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Generality of LCK regulation beyond nasopharyngeal carcinoma unknown\", \"Interplay between USP10 stabilization and UBR5 degradation not integrated\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How specific stress inputs are decoded to partition ATM signaling between ATMIN and NBS1, and the full genome-wide ATMIN transcriptional program beyond DYNLL1 and LCK, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of the ATM–ATMIN interface\", \"Conflicting data on replication-stress role unreconciled\", \"Determinants linking upstream lesion type to UBR5-dependent dissociation unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [8, 12, 20]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [8, 20]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 2, 7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [6, 8, 9]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [0, 2, 3]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [8, 20]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [10, 11, 17]},\n      {\"term_id\": \"R-HSA-8953897\", \"supporting_discovery_ids\": [7]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"ATM\", \"NBS1\", \"DYNLL1\", \"UBR5\", \"USP10\", \"WRNIP1\", \"PARP1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}