Affinage

ATRX

Transcriptional regulator ATRX · UniProt P46100

Length
2492 aa
Mass
282.6 kDa
Annotated
2026-04-28
100 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATRX is an SNF2-family ATP-dependent chromatin remodeler that, together with its chaperone partner DAXX, deposits histone variant H3.3 at heterochromatic repeats—including pericentromeric regions, telomeres, and rDNA loci—to establish and maintain repressive chromatin states essential for genome stability (PMID:29669917, PMID:34162889, PMID:22976303). ATRX directly binds RNA (Xist/RepA, TERRA) and G-quadruplex DNA structures: it serves as a specificity factor for PRC2 loading onto Xist RNA during X-chromosome inactivation, antagonizes TERRA at telomeres to regulate telomeric heterochromatin, and suppresses R-loops and G4-induced replicative stress at tandem repeats by acting upstream of the histone methyltransferase ESET (PMID:25417162, PMID:28666128, PMID:28487353, PMID:34162889). ATRX participates in multiple DNA damage response pathways: it protects stalled replication forks from MRE11-dependent degradation, promotes DNA repair synthesis and sister chromatid exchange during homologous recombination downstream of Rad51 by interacting with PCNA and RFC-1, and is required for proper sister chromatid cohesion and chromosome congression during mitosis (PMID:27171262, PMID:29937341, PMID:18227278). Loss of ATRX also impairs CTCF-mediated chromatin looping, disrupts imprinted gene silencing through its interaction with MeCP2 and cohesin, downregulates the cGAS/STING innate immune pathway, and sensitizes cells to DNA-damaging agents and innate immune agonists (PMID:34763709, PMID:20159591, PMID:37200088, PMID:38272925).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2004 Medium

    Establishing that the ATRX ortholog functions redundantly with Rb-family and HP1/NuRD chromatin regulators in cell fate specification revealed ATRX as a conserved chromatin remodeler integrated into core developmental transcriptional silencing networks.

    Evidence Genetic epistasis in C. elegans xnp-1;lin-35 double mutants with gonadal and larval developmental phenotypes

    PMID:15328017

    Open questions at the time
    • Biochemical activity of xnp-1 not characterized
    • Whether the redundancy with Rb reflects shared targets or parallel pathways was not resolved
    • Mammalian relevance not directly tested
  2. 2008 High

    Demonstrating that ATRX localizes to H3K9me3-marked pericentromeric heterochromatin and is required for sister chromatid cohesion and chromosome congression established its dual role in heterochromatin maintenance and mitotic fidelity.

    Evidence ChIP and FISH at pericentromeric/Y-chromosome regions in spermatogonia; live-cell imaging and siRNA in human cells and mouse neuroprogenitors showing mitotic defects

    PMID:18227278 PMID:18366812

    Open questions at the time
    • Molecular mechanism linking ATRX to cohesion establishment not identified
    • Whether ATPase activity is required for the mitotic role was untested
  3. 2010 High

    Showing that ATRX interacts with MeCP2 and cohesin at the H19 imprinting control region and is required for postnatal imprinted gene silencing connected ATRX chromatin remodeling to epigenetic regulation of imprinted loci.

    Evidence Reciprocal Co-IP of ATRX–MeCP2–cohesin, ChIP at H19 ICR, and conditional ATRX knockout mouse brain with imprinted gene derepression

    PMID:20159591

    Open questions at the time
    • Whether ATRX deposits H3.3 at imprinting control regions was not tested
    • Generality beyond H19 locus unclear
  4. 2012 Medium

    Revealing that ATRX/DAXX maintain transcriptional silencing and H3.3 incorporation at a defined chromatin locus—and that viral ICP0 degrades them to activate transcription—established the ATRX/DAXX complex as a repressive H3.3 chaperone exploited by herpesviruses.

    Evidence Live imaging and ChIP at a CMV-promoter transgene array in ATRX-positive vs. ATRX-negative cells; EBV BNRF1–DAXX Co-IP and ATRX/DAXX knockdown with viral reactivation readouts

    PMID:22102817 PMID:22976303

    Open questions at the time
    • Mechanism by which ICP0-mediated ATRX depletion alters chromatin was not structurally resolved
    • Whether all herpesvirus families exploit ATRX/DAXX was not addressed
  5. 2014 High

    Identifying ATRX as a high-affinity RNA-binding protein that loads PRC2 onto Xist RNA and directs PRC2 genome-wide revealed an unexpected RNA-mediated specificity function for a chromatin remodeler in Polycomb targeting.

    Evidence Unbiased proteomics, RNA immunoprecipitation, ChIP-seq, and ATRX knockout showing PRC2 redistribution and Polycomb target derepression

    PMID:25417162

    Open questions at the time
    • Structural basis for ATRX RNA binding not determined
    • Whether ATRX RNA binding is separable from its ATPase function was not tested
  6. 2016 High

    Showing that ATRX protects stalled replication forks from MRE11-dependent degradation and is required for BRCA1-RAD51 colocalization at forks placed ATRX in the replication stress response, and its loss in NHEJ explained increased DNA damage sensitivity in glioblastoma.

    Evidence DNA fiber assay with MRE11 inhibitor rescue in ATRX-null HeLa cells; NHEJ reporter assays and irradiation sensitivity in ATRX-deficient mouse GBM models

    PMID:26936505 PMID:27171262

    Open questions at the time
    • Direct NHEJ molecular mechanism for ATRX not characterized
    • Relative contribution of fork protection vs. NHEJ to genome instability not separated
  7. 2017 High

    Demonstrating that TERRA RNA competes with telomeric DNA for ATRX binding and that ATRX is recruited to R-loop-forming telomeric repeats established a model in which RNA–ATRX antagonism controls telomeric chromatin and R-loop suppression.

    Evidence TERRA ChIRP-seq and ATRX ChIP-seq showing reciprocal occupancy; R-loop detection by DRIP and S9.6 staining in ATRX-null cells

    PMID:28487353 PMID:28666128

    Open questions at the time
    • Whether ATRX resolves R-loops enzymatically or by remodeling was not determined
    • In vivo telomere phenotype of TERRA–ATRX antagonism not established
  8. 2018 High

    Placing ATRX downstream of Rad51 removal during HR repair synthesis and showing it deposits H3.3 with DAXX via interaction with PCNA/RFC-1 defined a chromatin assembly step essential for completing homologous recombination, while ATRX binding to G4 at imprinted loci linked G4 recognition to DNA methylation and synaptic function.

    Evidence Co-IP of ATRX–PCNA/RFC-1, siRNA with HR and SCE reporters; ATRX ChIP at G4 in Xlr3b, mutant mouse brain with dendritic transport defects rescued by G4-targeting compound; rDNA copy number loss in ATRX-depleted ES cells

    PMID:29669917 PMID:29785027 PMID:29937341

    Open questions at the time
    • Whether ATRX ATPase activity is required for HR repair synthesis not tested
    • Whether G4 binding and H3.3 deposition are mechanistically linked at rDNA not resolved
  9. 2019 Medium

    Characterizing ATRX in-frame fusion proteins that relocate from heterochromatin to active promoters and aberrantly activate REST showed how partial loss-of-function ATRX mutants can gain neomorphic transcriptional regulatory properties in cancer.

    Evidence ChIP-seq comparing ATRX IFF vs. wild-type localization, REST pathway and EZH2 inhibitor sensitivity analysis

    PMID:31631027

    Open questions at the time
    • Whether IFF-mediated REST activation occurs in primary tumors not confirmed
    • Structural basis for domain-loss-driven relocalization not determined
  10. 2021 High

    Establishing that ATRX associates with MCM helicase subunits and acts upstream of ESET-mediated heterochromatin to protect against G4-induced replication stress unified the G4-binding and heterochromatin functions into a single replication protection pathway, while ATRX binding at cell-cycle gene regulatory elements explained checkpoint defects upon ATRX loss.

    Evidence Co-IP of ATRX–MCM, domain mutant rescue, G4 ChIP-seq, epistasis with ESET; ChIP-seq at CHEK1 regulatory elements with ATM inhibitor rescue in GBM mouse models

    PMID:34162889 PMID:35021084

    Open questions at the time
    • Whether ATRX directly unwinds G4 or recruits dedicated G4 helicases is unknown
    • Mechanism connecting ATRX to CHEK1 transcriptional regulation not molecularly defined
  11. 2022 Medium

    Multi-omic studies expanded ATRX's chromatin role to euchromatic regulatory elements, CTCF loop organization, p53 chromatin binding, and TERRA-dependent modulation of G4 abundance, revealing that ATRX loss produces stochastic, cell-variable chromatin perturbation genome-wide.

    Evidence ATRX ChIP, ATAC-seq, H3.3 ChIP-seq in erythroid cells; CUT&TAG for CTCF in ATRX-KO glioma; p53 ChIP-seq/ATAC-seq in DAXX/ATRX-KO glioma; G4 ChIP-seq after TERRA knockdown with ATRX epistasis

    PMID:34763709 PMID:35710802 PMID:36028493 PMID:36440760

    Open questions at the time
    • Whether stochastic chromatin effects arise from H3.3 deposition failure or ATPase-dependent remodeling loss is unresolved
    • Direct ATRX–CTCF physical interaction not demonstrated
    • Causal link between ATRX loss and p53 chromatin binding defect not fully separated from H3.3 loss
  12. 2022 Medium

    Demonstrating that ATRX loss downregulates the cGAS/STING innate immune pathway and sensitizes tumors to irradiation and innate immune agonists connected ATRX chromatin remodeling to innate immune competence, with therapeutic implications.

    Evidence Primary Atrx-deleted mouse sarcoma model with cGAS/STING protein analysis, irradiation, and oncolytic virus treatment; ATRX-KO glioma cells treated with dsRNA agonists showing enhanced T-cell infiltration in vivo

    PMID:37200088 PMID:38272925

    Open questions at the time
    • Mechanism by which ATRX loss suppresses cGAS/STING not molecularly defined
    • Whether the immune phenotype is tumor-type specific is unclear
    • Contribution of co-occurring IDH1 mutation confounds interpretation in glioma

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for ATRX's RNA and G-quadruplex binding specificity, whether ATRX directly resolves G4/R-loop structures via its ATPase or acts indirectly through chromatin remodeling, and the mechanism linking ATRX loss to cGAS/STING pathway suppression.
  • No structural model of ATRX bound to RNA or G4 DNA
  • ATPase-dependent vs. ATPase-independent functions not fully separated in vivo
  • Mechanism of ATRX regulation of cGAS/STING signaling unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 3 GO:0003677 DNA binding 2 GO:0003723 RNA binding 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0140657 ATP-dependent activity 2
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-4839726 Chromatin organization 4 R-HSA-73894 DNA Repair 3 R-HSA-1640170 Cell Cycle 2 R-HSA-168256 Immune System 2 R-HSA-69306 DNA Replication 2
Partners
CTCFDAXXEZH2H3F3AMECP2PCNARFC1
Complex memberships
ATRX-DAXX

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 ATRX functions as a high-affinity RNA-binding protein that directly interacts with RepA/Xist RNA to promote loading of PRC2 onto Xist RNA and its spread in cis along the X chromosome; loss of ATRX leads to failure of PRC2 loading onto Xist RNA and genome-wide redistribution of PRC2 with derepression of Polycomb responsive genes. Unbiased proteomics (mass spectrometry), RNA immunoprecipitation, ChIP-seq, loss-of-function (ATRX knockdown/knockout) with functional readouts (PRC2 distribution, gene expression) Cell High 25417162
2017 TERRA RNA competes with telomeric DNA for ATRX binding, suppresses ATRX localization to telomeres, and ensures telomeric stability; TERRA and ATRX are functionally antagonistic at shared target genes (TERRA activates, ATRX represses); depleting TERRA increases telomerase activity and induces telomeric pathologies. Genomic (ChIRP-seq for TERRA targets), proteomic (mass spectrometry interactome), ATRX ChIP-seq, TERRA knockdown with telomere phenotype readouts (TIFs, telomere length) Cell High 28666128
2018 ATRX operates downstream of Rad51 removal during homologous recombination and interacts with PCNA and RFC-1 to promote DNA repair synthesis; ATRX and DAXX deposit histone H3.3 during DNA repair synthesis; depletion of ATRX abolishes DNA repair synthesis and sister chromatid exchange at exogenously induced DSBs. Co-immunoprecipitation (ATRX–PCNA, ATRX–RFC-1 interactions), siRNA knockdown of ATRX/DAXX/H3.3 with HR reporter assays, sister chromatid exchange assays, proximity ligation assay Molecular cell High 29937341
2008 Loss of ATRX causes defective sister chromatid cohesion and chromosome congression at the metaphase plate, prolonging prometaphase-to-metaphase transition; ATRX is required for normal mitotic progression in human cultured cells and in neuroprogenitors in vivo. Live cell imaging of ATRX-depleted cells, siRNA knockdown, analysis of embryonic mouse brain neuroprogenitors in vivo (mitotic defects by immunostaining) The Journal of cell biology High 18227278
2010 ATRX interacts with MeCP2 and cohesin in the brain and colocalizes at the H19 imprinting control region (ICR); loss of ATRX alters enrichment of cohesin, CTCF, and histone modifications at the H19 ICR and interferes with postnatal silencing of maternal H19 and a network of imprinted genes. Co-immunoprecipitation (ATRX–MeCP2–cohesin), chromatin immunoprecipitation (ChIP), ATRX conditional knockout mouse brain, gene expression analysis Developmental cell High 20159591
2017 ATRX recruitment to telomeric repeats depends on repeat number, transcription orientation, and the formation of RNA-DNA hybrids (R-loops) at transcribed telomeric repeats; loss of ATRX is associated with increased R-loop formation, suggesting ATRX suppresses deleterious DNA secondary structures at telomeres. ChIP (ATRX at telomeric repeats), R-loop detection (S9.6 antibody immunostaining/DRIP), ATRX loss-of-function with quantification of R-loops EMBO reports High 28487353
2021 ATRX associates with MCM replication complex subunits; both the helicase domain of ATRX and its H3.3 chaperone function are required to protect cells from G-quadruplex (G4)-induced replicative stress; ATRX acts upstream of heterochromatin formation mediated by the histone methyltransferase ESET, which is the critical molecular event protecting cells from G4-mediated stress. Co-immunoprecipitation (ATRX–MCM subunits), domain mutant rescue experiments, G4 ChIP-seq, proximity ligation assay, ESET epistasis experiments, ATRX knockout cell lines Nature communications High 34162889
2016 Loss of ATRX impairs nonhomologous end joining (NHEJ) DNA repair, increases sensitivity to DNA double-strand break-inducing agents, and results in increased genetic instability in glioblastoma models. ATRX-deficient mouse GBM model (in vivo), NHEJ reporter assays, DNA damage sensitivity assays (γH2AX, comet assay), genome-wide mutation analysis Science translational medicine Medium 26936505
2016 ATRX is required to protect stalled replication forks within heterochromatin; in ATRX-null cells, stalled replication forks undergo MRE11-dependent degradation, and BRCA1-RAD51 colocalization at stalled forks is impaired; DAXX also contributes to fork protection. DNA fiber assay, MRE11 inhibitor rescue (mirin), PARP-1 activity measurements, BRCA1/RAD51 colocalization (immunofluorescence), ATRX/DAXX knockout HeLa cells and conditional mouse KO Cell death & disease High 27171262
2018 ATRX depletion in mouse ES cells leads to selective loss of ribosomal RNA gene (rDNA) copy number, caused by disruption of H3.3 deposition and failure of heterochromatin formation at rDNA repeats; ATRX-depleted cells show reduced rRNA transcription and increased sensitivity to RNA Pol I inhibitor CX5461. ATRX depletion (shRNA) in mouse ES cells, rDNA copy number analysis (qPCR/sequencing), H3.3 ChIP at rDNA repeats, Pol I transcription assays, CX5461 sensitivity assays Proceedings of the National Academy of Sciences of the United States of America High 29669917
2012 ATRX and DAXX are enriched at a CMV-promoter transgene array and are required to maintain transcriptional repression and chromatin assembly (histone H3.3 incorporation) at this locus; ICP0 (HSV-1 E3 ubiquitin ligase) depletes ATRX and DAXX from the array to activate transcription; ATRX-negative U2OS cells cannot maintain repression at the same array. Single-cell fluorescence live imaging, ChIP at transgene array, ATRX/DAXX depletion and ICP0 overexpression with transcriptional readouts, comparison of ATRX-positive (HeLa) vs ATRX-negative (U2OS) cells Journal of cell science Medium 22976303
2011 EBV tegument protein BNRF1 interacts with DAXX at PML nuclear bodies and disrupts the DAXX-ATRX chromatin remodeling complex; disruption of DAXX-ATRX promotes viral early gene expression; knockdown of DAXX and ATRX independently induces EBV reactivation from latency in lymphoblastoid cells, indicating DAXX-ATRX complex represses viral chromatin. Co-immunoprecipitation (BNRF1–DAXX interaction), domain mapping, shRNA knockdown of DAXX/ATRX with EBV reactivation assays, RT-PCR for viral gene expression PLoS pathogens Medium 22102817
2008 ATRX (as a SNF2-family ATPase) is localized at pericentromeric heterochromatin and associates with H3K9me3 marks and Y chromosome-specific sequences in neonatal spermatogonia, suggesting a role in heterochromatinization independent of DNA methylation. Chromatin immunoprecipitation (ChIP) with H3K9me3 and ATRX antibodies, fluorescence immunostaining, FISH, ChIP-seq at Y chromosome sequences BMC molecular biology Medium 18366812
2018 ATRX binds G-quadruplex (G4) structures in CpG islands of the imprinted Xlr3b gene and regulates its expression by recruiting DNA methyltransferases; Atrx mutation causes aberrant Xlr3b upregulation in mouse brain, leading to inhibition of dendritic mRNA transport and synaptic dysfunction. ChIP (ATRX at Xlr3b G4 structures), G4-binding assays, ATRX mutant mouse model, Xlr3b overexpression functional studies, rescue with G4-binding compound (5-ALA) Nature medicine High 29785027
2022 DAXX and ATRX knockout in glioma cells leads to defects in p53 chromatin binding and DNA damage response, with genome-wide reduction in p53 DNA-binding and loss of chromatin accessibility at p53 response elements; these changes are associated with depletion of histone H3.3 and accumulation of γH2AX at p53 sites including subtelomeres. ChIP-seq (p53 binding), ATAC-seq (chromatin accessibility), RNA-seq (p53 pathway), γH2AX immunostaining, DAXX/ATRX knockout cell lines Nature communications Medium 36028493
2022 ATRX binds active regulatory elements in euchromatin in addition to heterochromatic repeats; ATRX mutations lead to reduced chromatin accessibility, altered histone modifications (H3.3 deposition), and perturbed transcription factor binding in a stochastic, cell-to-cell variable manner in erythroid cells. Improved ChIP protocol for ATRX at euchromatin, ATAC-seq, H3.3 ChIP-seq, RNA-seq in erythroid cells, ATRX mutant cells Nature communications Medium 35710802
2019 ATRX in-frame fusion (IFF) proteins lacking key chromatin interaction domains but retaining the SWI/SNF-like helicase region are redistributed from H3K9me3-enriched heterochromatin to promoters of active genes; ATRX IFF activates REST, which promotes silencing of neuronal differentiation genes. ChIP-seq (ATRX IFF localization vs. wild-type), H3K9me3 ChIP-seq, REST binding analysis, gene expression analysis, EZH2 inhibitor sensitivity assays Cancer cell Medium 31631027
2021 ATRX loss leads to a global depletion of CTCF association with DNA and gene dysregulation along associated chromatin loops, and protects glioma cells from therapy-induced senescence; ATRX-knockout murine gliomas are more heavily infiltrated by immunosuppressive monocytic-lineage cells. scRNA-seq, scATAC-seq, CUT&TAG for CTCF, ATRX knockout murine glioma model, single-cell analysis of human ATRX-mutant vs. wild-type tumors Genome biology Medium 34763709
2022 TERRA modulates ATRX occupancy on repetitive sequences and genes; TERRA prevents ATRX from binding to subtelomeric regions and represses H3K9me3 formation; loss of TERRA increases ATRX occupancy and reduces DNA G-quadruplex abundance at transcription start sites, leading to gene repression that is alleviated by ATRX loss. G4 ChIP-seq, ATRX ChIP-seq after TERRA knockdown, H3K9me3 ChIP, immunostaining for DNA G4, epistasis between TERRA knockdown and ATRX silencing Nucleic acids research Medium 36440760
2022 ATRX loss results in downregulation of the cGAS/STING innate immune signaling pathway at multiple levels (not via mutation or transcriptional downregulation of pathway components), and sensitizes sarcoma cells to irradiation and oncolytic herpesvirus (TVEC); Atrx-deleted irradiated tumors show increased persistent DNA damage, telomere dysfunction, and mitotic catastrophe. Primary mouse soft tissue sarcoma model with Atrx deletion, cGAS/STING pathway protein/RNA analysis, irradiation and TVEC treatment with survival/immune readouts, DNA damage markers The Journal of clinical investigation Medium 37200088
2004 In C. elegans, xnp-1 (ATRX ortholog) acts redundantly with lin-35/Rb and functions in combination with RB, HP1, and the NuRD complex to control somatic gonad development and larval development; xnp-1 and lin-35 double mutants show severe gonadal defects and loss of cell fate specification. C. elegans genetic epistasis (double mutants: xnp-1;lin-35, xnp-1;hpl-2), transgene expression control assays, developmental phenotype analysis Developmental biology Medium 15328017
2021 ATRX loss in glioblastoma cells results in reduced Checkpoint Kinase 1 (CHEK1) expression and early G2/M entry after irradiation; ATRX binds regulatory elements of cell-cycle phase transition genes; ATRX-deficient cells show enhanced ATM activation with irradiation, and ATM inhibition doubles median survival in mice bearing ATRX-deficient GBM. ChIP-seq (ATRX at cell-cycle gene regulatory elements), ATRX knockout GBM cell lines and mouse intracranial model, Chk1 expression analysis, ATM inhibitor (AZD0156) in vivo treatment Cell reports Medium 35021084
2024 ATRX-deficient glioma cells are sensitive to dsRNA-based innate immune agonism and exhibit impaired lethality and increased T-cell infiltration in vivo; ATRX loss primes cells for dsRNA recognition while co-expressed IDH1R132H mutation reversibly suppresses baseline innate immune gene expression and cytokine production. ATRX knockout glioma models with/without IDH1R132H, dsRNA agonist treatment, innate immune gene expression (RNA-seq), T-cell infiltration analysis (flow cytometry/IHC), IDH1 inhibitor rescue Nature communications Medium 38272925

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Catalysis of homologous DNA pairing by yeast Rad51 and Rad54 proteins. Nature 359 9590697
2003 In vivo roles of Rad52, Rad54, and Rad55 proteins in Rad51-mediated recombination. Molecular cell 307 12887906
2016 ATRX loss promotes tumor growth and impairs nonhomologous end joining DNA repair in glioma. Science translational medicine 223 26936505
2002 Rad54, a Swi2/Snf2-like recombinational repair protein, disassembles Rad51:dsDNA filaments. Molecular cell 219 12453424
2017 TERRA RNA Antagonizes ATRX and Protects Telomeres. Cell 216 28666128
2000 Superhelicity-driven homologous DNA pairing by yeast recombination factors Rad51 and Rad54. Molecular cell 189 11030336
2018 ATRX, DAXX or MEN1 mutant pancreatic neuroendocrine tumors are a distinct alpha-cell signature subgroup. Nature communications 172 30315258
2014 ATRX directs binding of PRC2 to Xist RNA and Polycomb targets. Cell 171 25417162
1997 RDH54, a RAD54 homologue in Saccharomyces cerevisiae, is required for mitotic diploid-specific recombination and repair and for meiosis. Genetics 169 9409819
1999 Yeast Rad54 promotes Rad51-dependent homologous DNA pairing via ATP hydrolysis-driven change in DNA double helix conformation. The Journal of biological chemistry 167 10506208
2008 Mutations in the chromatin-associated protein ATRX. Human mutation 138 18409179
2010 ATRX partners with cohesin and MeCP2 and contributes to developmental silencing of imprinted genes in the brain. Developmental cell 136 20159591
2000 Mouse RAD54 affects DNA double-strand break repair and sister chromatid exchange. Molecular and cellular biology 135 10757799
2008 Loss of ATRX leads to chromosome cohesion and congression defects. The Journal of cell biology 132 18227278
2006 Visualization of Rad54, a chromatin remodeling protein, translocating on single DNA molecules. Molecular cell 132 16818238
2018 ATRX Promotes DNA Repair Synthesis and Sister Chromatid Exchange during Homologous Recombination. Molecular cell 119 29937341
2011 Functions of the Snf2/Swi2 family Rad54 motor protein in homologous recombination. Biochimica et biophysica acta 119 21704205
2002 Homologous DNA pairing by human recombination factors Rad51 and Rad54. The Journal of biological chemistry 118 12205100
2011 EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription. PLoS pathogens 116 22102817
2017 The chromatin remodelling factor ATRX suppresses R-loops in transcribed telomeric repeats. EMBO reports 113 28487353
2002 RAD18 and RAD54 cooperatively contribute to maintenance of genomic stability in vertebrate cells. The EMBO journal 113 12374756
2015 IDH mutation, 1p19q codeletion and ATRX loss in WHO grade II gliomas. Oncotarget 107 26210286
2013 The chromatin remodeller ATRX: a repeat offender in human disease. Trends in biochemical sciences 98 23916100
2016 ATRX immunostaining predicts IDH and H3F3A status in gliomas. Acta neuropathologica communications 95 27311324
1996 Isolation of the Schizosaccharomyces pombe RAD54 homologue, rhp54+, a gene involved in the repair of radiation damage and replication fidelity. Journal of cell science 95 8834792
1991 Sequence of RAD54, a Saccharomyces cerevisiae gene involved in recombination and repair. Gene 94 1916269
2020 MYCN amplification and ATRX mutations are incompatible in neuroblastoma. Nature communications 90 32060267
2017 The Role of ATRX in Glioma Biology. Frontiers in oncology 84 29034211
2017 New Molecular Considerations for Glioma: IDH, ATRX, BRAF, TERT, H3 K27M. Current neurology and neuroscience reports 81 28271343
2016 Nek1 Regulates Rad54 to Orchestrate Homologous Recombination and Replication Fork Stability. Molecular cell 80 27264870
2021 ATRX promotes heterochromatin formation to protect cells from G-quadruplex DNA-mediated stress. Nature communications 78 34162889
2018 Ribosomal DNA copy loss and repeat instability in ATRX-mutated cancers. Proceedings of the National Academy of Sciences of the United States of America 78 29669917
2020 Rad54 Drives ATP Hydrolysis-Dependent DNA Sequence Alignment during Homologous Recombination. Cell 77 32502392
2011 ATP-dependent and independent functions of Rad54 in genome maintenance. The Journal of cell biology 77 21357745
2023 ATRX, a guardian of chromatin. Trends in genetics : TIG 75 36894374
2006 Isolation and characterization of the RAD54 gene from Arabidopsis thaliana. The Plant journal : for cell and molecular biology 75 17227544
1999 Mutations in the RAD54 recombination gene in primary cancers. Oncogene 73 10362365
2016 The Role of ATRX in the Alternative Lengthening of Telomeres (ALT) Phenotype. Genes 72 27657132
2006 Werner syndrome protein participates in a complex with RAD51, RAD54, RAD54B and ATR in response to ICL-induced replication arrest. Journal of cell science 72 17118963
2016 Stalled replication forks within heterochromatin require ATRX for protection. Cell death & disease 71 27171262
2021 Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations. The Journal of clinical endocrinology and metabolism 68 33106857
2018 Targeting G-quadruplex DNA as cognitive function therapy for ATR-X syndrome. Nature medicine 68 29785027
2019 ATRX In-Frame Fusion Neuroblastoma Is Sensitive to EZH2 Inhibition via Modulation of Neuronal Gene Signatures. Cancer cell 63 31631027
2007 Homology-driven chromatin remodeling by human RAD54. Nature structural & molecular biology 63 17417655
1999 Detection of loss of heterozygosity at RAD51, RAD52, RAD54 and BRCA1 and BRCA2 loci in breast cancer: pathological correlations. British journal of cancer 63 10507777
2020 The bromodomain containing protein BRD-9 orchestrates RAD51-RAD54 complex formation and regulates homologous recombination-mediated repair. Nature communications 61 32457312
2002 Analysis of mouse Rad54 expression and its implications for homologous recombination. DNA repair 61 12531026
2016 Utility of ATRX immunohistochemistry in diagnosis of adult diffuse gliomas. Histopathology 57 26741321
1997 Determination of the genomic structure of the XNP/ATRX gene encoding a potential zinc finger helicase. Genomics 57 9244431
2006 Terminal association of Rad54 protein with the Rad51-dsDNA filament. Proceedings of the National Academy of Sciences of the United States of America 55 16785421
2022 ATRX loss in glioma results in dysregulation of cell-cycle phase transition and ATM inhibitor radio-sensitization. Cell reports 53 35021084
2016 Immunohistochemical Analysis of ATRX, IDH1 and p53 in Glioblastoma and Their Correlations with Patient Survival. Journal of Korean medical science 53 27478330
2015 Emerging roles of ATRX in cancer. Epigenomics 53 26646632
1996 A novel mutation in the putative DNA helicase XH2 is responsible for male-to-female sex reversal associated with an atypical form of the ATR-X syndrome. American journal of human genetics 53 8651295
1996 Splicing mutation in the ATR-X gene can lead to a dysmorphic mental retardation phenotype without alpha-thalassemia. American journal of human genetics 52 8644709
2020 Correlation between IDH, ATRX, and TERT promoter mutations in glioma. Brain tumor pathology 51 32227259
2007 Metabolic syndrome and C-reactive protein in the general population: JMS Cohort Study. Circulation journal : official journal of the Japanese Circulation Society 51 17186974
2000 A novel human rad54 homologue, Rad54B, associates with Rad51. The Journal of biological chemistry 49 10851248
2007 Single molecule imaging of Tid1/Rdh54, a Rad54 homolog that translocates on duplex DNA and can disrupt joint molecules. The Journal of biological chemistry 48 17704061
2012 Single-cell analysis of Daxx and ATRX-dependent transcriptional repression. Journal of cell science 46 22976303
2021 Mutations inhibiting KDM4B drive ALT activation in ATRX-mutated glioblastomas. Nature communications 44 33972520
2021 ATRX regulates glial identity and the tumor microenvironment in IDH-mutant glioma. Genome biology 44 34763709
2022 DAXX-ATRX regulation of p53 chromatin binding and DNA damage response. Nature communications 41 36028493
2014 Altered global histone-trimethylation code and H3F3A-ATRX mutation in pediatric GBM. Journal of neuro-oncology 41 25479829
2021 Loss of ATRX confers DNA repair defects and PARP inhibitor sensitivity. Translational oncology 40 34118569
2019 In vitro role of Rad54 in Rad51-ssDNA filament-dependent homology search and synaptic complexes formation. Nature communications 40 31492866
2013 ATRX and the replication of structured DNA. Current opinion in genetics & development 40 23453691
2014 Clinical features of ATRX or DAXX mutated neuroblastoma. Journal of pediatric surgery 37 25487495
2005 Mutation in the 5' alternatively spliced region of the XNP/ATR-X gene causes Chudley-Lowry syndrome. European journal of human genetics : EJHG 37 15508018
2022 The chromatin remodeller ATRX facilitates diverse nuclear processes, in a stochastic manner, in both heterochromatin and euchromatin. Nature communications 36 35710802
2019 Targeting Telomerase and ATRX/DAXX Inducing Tumor Senescence and Apoptosis in the Malignant Glioma. International journal of molecular sciences 36 30625996
2018 Significance of TERT and ATRX mutations in glioma. Oncology letters 35 30655743
2002 Expanding phenotype of XNP mutations: mild to moderate mental retardation. American journal of medical genetics 35 12116232
2008 Human Rad54 protein stimulates human Mus81-Eme1 endonuclease. Proceedings of the National Academy of Sciences of the United States of America 34 19017809
2021 The Multiple Facets of ATRX Protein. Cancers 33 34062956
2023 The Chromatin Remodeler ATRX: Role and Mechanism in Biology and Cancer. Cancers 32 37190157
2022 TOP3A amplification and ATRX inactivation are mutually exclusive events in pediatric osteosarcomas using ALT. EMBO molecular medicine 32 35920001
2014 Nap1 stimulates homologous recombination by RAD51 and RAD54 in higher-ordered chromatin containing histone H1. Scientific reports 32 24798879
2007 Interactions of human rad54 protein with branched DNA molecules. The Journal of biological chemistry 32 17545145
2004 lin-35/Rb and xnp-1/ATR-X function redundantly to control somatic gonad development in C. elegans. Developmental biology 32 15328017
1997 Characterization of the human homologue of RAD54: a gene located on chromosome 1p32 at a region of high loss of heterozygosity in breast tumors. Cancer research 32 9192813
2017 RAD54 forms DNA repair foci in response to DNA damage in living plant cells. The Plant journal : for cell and molecular biology 31 28155243
2016 Rad51 and Rad54 promote noncrossover recombination between centromere repeats on the same chromatid to prevent isochromosome formation. Nucleic acids research 30 27697832
2011 A novel role for RAD54: this host protein modulates geminiviral DNA replication. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 30 22171001
2009 BLM helicase stimulates the ATPase and chromatin-remodeling activities of RAD54. Journal of cell science 30 19671661
2008 Association of ATRX with pericentric heterochromatin and the Y chromosome of neonatal mouse spermatogonia. BMC molecular biology 30 18366812
2018 Loss of ATRX/DAXX expression and alternative lengthening of telomeres in uterine leiomyomas. Cancer 29 30423196
2011 Protein-DNA interactions in high speed AFM: single molecule diffusion analysis of human RAD54. Integrative biology : quantitative biosciences from nano to macro 28 21986699
2010 Reduced expression of the ATRX gene, a chromatin-remodeling factor, causes hippocampal dysfunction in mice. Hippocampus 28 20865721
2005 XNP-1/ATR-X acts with RB, HP1 and the NuRD complex during larval development in C. elegans. Developmental biology 28 15649460
2020 NUCKS1 promotes RAD54 activity in homologous recombination DNA repair. The Journal of cell biology 27 32876692
2018 Alternative lengthening of telomeres phenotype and loss of ATRX expression in sarcomas. Oncology letters 27 29725455
2022 TERRA regulates DNA G-quadruplex formation and ATRX recruitment to chromatin. Nucleic acids research 26 36440760
2003 Genome instability in rad54 mutants of Saccharomyces cerevisiae. Nucleic acids research 26 12560498
2022 Mutational spectrum of ATRX aberrations in neuroblastoma and associated patient and tumor characteristics. Cancer science 25 35384159
2011 ATRX in chromatin assembly and genome architecture during development and disease. Biochemistry and cell biology = Biochimie et biologie cellulaire 25 21851155
1996 A point mutation in the XNP gene, associated with an ATR-X phenotype without alpha-thalassemia. European journal of human genetics : EJHG 25 9043863
2023 Atrx deletion impairs CGAS/STING signaling and increases sarcoma response to radiation and oncolytic herpesvirus. The Journal of clinical investigation 24 37200088
2024 Interplay between ATRX and IDH1 mutations governs innate immune responses in diffuse gliomas. Nature communications 23 38272925
2023 TLK1-mediated RAD54 phosphorylation spatio-temporally regulates Homologous Recombination Repair. Nucleic acids research 23 37439356