{"gene":"TG_261580","gene_symbol":"","run_date":"2026-09-08T12:58:25","timeline":{"discoveries":[{"year":2009,"finding":"Toxoplasma gondii H2AX contains a complete SQ(E/D)φ motif (where φ denotes a hydrophobic residue) that is phosphorylated in response to DNA damage, whereas the canonical H2A1, which also has an SQ motif, lacks this complete motif and is not equivalently phosphorylated.","method":"Sequence analysis of SQ motif combined with detection of H2AX phosphorylation after DNA damage treatment","journal":"Journal of molecular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct phosphorylation detected experimentally in the parasite with motif-level mechanistic explanation, single lab but two complementary approaches","pmids":["19607843"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2009,"finding":"A novel H2B variant (H2Bv) interacts with H2AZ and H2A1 but NOT with H2AX, indicating H2AX forms nucleosomes of distinct composition from the other H2A variants.","method":"Co-immunoprecipitation / interaction assay between H2A variants and H2Bv","journal":"Journal of molecular biology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single-lab Co-IP result with explicit negative control for H2AX, single method","pmids":["19607843"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2009,"finding":"ChIP revealed that H2AX is enriched at repressed genes and at the silent TgIRE repeat element, while H2AZ is enriched at active genes, indicating H2AX marks transcriptionally silenced chromatin regions.","method":"Chromatin immunoprecipitation (ChIP)","journal":"Journal of molecular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP directly maps genomic enrichment, single lab, single method","pmids":["19607843"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2009,"finding":"H2AX localizes to silenced chromatin areas during bradyzoite differentiation, and h2ax transcript levels increase in bradyzoites generated both in vitro and in vivo (G0-arrested), consistent with a role in chromatin silencing during stage conversion.","method":"Quantitative RT-PCR for transcript levels; localization by immunofluorescence/ChIP during bradyzoite differentiation","journal":"Journal of molecular biology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — transcript and localization data across two differentiation conditions (in vitro and in vivo), single lab","pmids":["19607843"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2010,"finding":"Overexpression of TgMYST-B (a MYST family lysine acetyltransferase) in Toxoplasma gondii leads to increased levels of phosphorylated H2AX, placing TgMYST-B upstream of H2AX phosphorylation in the DNA damage response pathway.","method":"Overexpression of recombinant tagged TgMYST-B with detection of phospho-H2AX levels; pharmacological inhibition of ATM kinase or KATs reverses associated phenotype","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic overexpression with pharmacological epistasis and quantified H2AX phosphorylation readout, single lab","pmids":["20159970"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2010,"finding":"The increase in phospho-H2AX upon TgMYST-B overexpression is dependent on ATM kinase activity, as pharmacological inhibition of ATM kinase reverses this effect, placing ATM kinase as the writer of H2AX phosphorylation in the T. gondii DNA damage response.","method":"ATM kinase pharmacological inhibition combined with phospho-H2AX level measurement in TgMYST-B-overexpressing parasites","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epistasis via pharmacological inhibitor with quantified phospho-H2AX readout, single lab","pmids":["20159970"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"finding":"T. gondii infection of primary host endothelial cells induces DNA double-strand breaks in a strain-dependent manner, as quantified by γ-H2AX (phosphorylated H2AX) levels, with the RH strain driving the most prominent effect; this is accompanied by activation of the ATM-dependent homologous recombination pathway in host cells.","method":"γ-H2AX quantification by microscopy, comet assay, and measurement of HR/NHEJ pathway markers in T. gondii-infected primary endothelial cells","journal":"Frontiers in cellular and infection microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (comet assay, γ-H2AX quantification, pathway marker analysis) in a single lab; γ-H2AX used as a readout for host cell H2AX phosphorylation, not parasite H2AX","pmids":["38524184"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"RH"},{"species":"Toxoplasma gondii","strain":"Me49"},{"species":"Toxoplasma gondii","strain":"NED"}]}],"current_model":"Toxoplasma gondii H2AX bears a complete SQ(E/D)φ motif that is phosphorylated by ATM kinase in response to DNA damage (a process facilitated upstream by the MYST acetyltransferase TgMYST-B), associates with silenced and repressed chromatin regions (not active genes), forms compositionally distinct nucleosomes that exclude the H2Bv variant, and accumulates at silenced loci during bradyzoite differentiation, suggesting a dual role in the DNA damage response and chromatin-based transcriptional silencing."},"narrative":{"mechanistic_narrative":"Toxoplasma gondii H2AX is a histone H2A variant that couples the DNA damage response to chromatin-based transcriptional silencing [PMID:19607843]. Unlike the canonical H2A1, which carries only a partial SQ motif, H2AX bears a complete SQ(E/D)φ motif that is phosphorylated upon DNA damage [PMID:19607843], and this phosphorylation is written by ATM kinase and promoted upstream by the MYST-family acetyltransferase TgMYST-B [PMID:20159970]. H2AX assembles into nucleosomes of distinct composition, being excluded from interaction with the H2Bv variant that partners H2AZ and H2A1 [PMID:19607843]. Genome-wide, H2AX is enriched at repressed genes and the silent TgIRE repeat rather than active genes, and it accumulates at silenced chromatin during bradyzoite differentiation, when its transcript is upregulated [PMID:19607843]. Beyond these findings, the structural and biochemical details of how H2AX phosphorylation is coordinated with silencing have not been characterized in the available corpus.","teleology":[{"year":2009,"claim":"It was unknown whether T. gondii encodes a bona fide DNA-damage-responsive H2A variant; showing H2AX carries a complete SQ(E/D)φ motif phosphorylated after DNA damage established it as the parasite's γ-H2AX equivalent and distinguished it from canonical H2A1.","evidence":"sequence analysis of the SQ motif plus detection of H2AX phosphorylation after DNA damage in the parasite","pmids":["19607843"],"confidence":"Medium","gaps":["Does not identify the kinase responsible","Does not resolve the functional consequence of phosphorylation at damage sites"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2009,"claim":"Whether H2AX forms compositionally distinct nucleosomes was unresolved; demonstrating that the H2Bv variant partners H2AZ and H2A1 but not H2AX established that H2AX-containing nucleosomes are biochemically distinct from other H2A variant nucleosomes.","evidence":"Co-immunoprecipitation between H2A variants and H2Bv with H2AX as an explicit negative","pmids":["19607843"],"confidence":"Medium","gaps":["Single Co-IP without reciprocal or reconstitution validation","Does not define which H2B partners H2AX"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2009,"claim":"The chromatin context of H2AX was unknown; ChIP mapping showed H2AX marks repressed genes and the silent TgIRE element while H2AZ marks active genes, and it accumulates at silenced loci with upregulated transcript during bradyzoite differentiation, establishing a role in transcriptional silencing and stage conversion.","evidence":"ChIP genomic mapping, quantitative RT-PCR, and localization during in vitro and in vivo bradyzoite differentiation","pmids":["19607843"],"confidence":"Medium","gaps":["Does not establish whether H2AX deposition is a cause or consequence of silencing","Does not connect the silencing role to the DNA damage phosphorylation role"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2010,"claim":"The writer and upstream regulator of H2AX phosphorylation were undefined; placing TgMYST-B upstream and ATM kinase as the writer established the signalling axis for H2AX phosphorylation in the parasite DNA damage response.","evidence":"TgMYST-B overexpression with phospho-H2AX readout and pharmacological ATM inhibition epistasis","pmids":["20159970"],"confidence":"Medium","gaps":["Relies on pharmacological inhibition rather than genetic ablation of ATM","Does not define how TgMYST-B acetylation feeds into ATM activation"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"claim":"It was unclear whether infection perturbs host genome integrity; γ-H2AX quantification showed T. gondii induces host DNA double-strand breaks and ATM-dependent homologous recombination in a strain-dependent manner, with RH most potent.","evidence":"γ-H2AX microscopy, comet assay, and HR/NHEJ marker analysis in infected primary endothelial cells (host-cell H2AX readout)","pmids":["38524184"],"confidence":"Medium","gaps":["γ-H2AX here reports host-cell, not parasite, H2AX","Does not identify the parasite effector driving host DSBs"],"attribution":[{"species":"Toxoplasma gondii","strain":"RH"},{"species":"Toxoplasma gondii","strain":"Me49"},{"species":"Toxoplasma gondii","strain":"NED"}]},{"year":null,"claim":"How the DNA-damage phosphorylation function of H2AX is mechanistically integrated with its role in transcriptional silencing, and the structural basis of its distinct nucleosome composition, remain open.","evidence":"no direct evidence in the available corpus","pmids":[],"confidence":"Medium","gaps":["No structural model of H2AX nucleosomes","No genetic loss-of-function characterization of parasite H2AX","Mechanistic link between silencing and DNA damage roles unresolved"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["H2AX-containing nucleosome (distinct composition, excludes H2Bv)"],"partners":["ATM KINASE (WRITER OF H2AX PHOSPHORYLATION)","TGMYST-B (UPSTREAM ACETYLTRANSFERASE PROMOTING H2AX PHOSPHORYLATION)"],"other_free_text":["H2AX bears a complete SQ(E/D)φ motif phosphorylated on DNA damage, unlike canonical H2A1 [#0]","H2Bv partners H2AZ and H2A1 but not H2AX [#1]","h2ax transcript upregulated during bradyzoite differentiation [#3]","γ-H2AX used as host-cell DSB readout during infection; parasite induces strain-dependent host DNA damage [#6]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"19607843","id":"PMC_19607843","title":"Toxoplasma H2A variants reveal novel insights into nucleosome composition and functions for this histone family.","date":"2009","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/19607843","citation_count":51,"is_preprint":false},{"pmid":"20159970","id":"PMC_20159970","title":"MYST family lysine acetyltransferase facilitates ataxia telangiectasia mutated (ATM) kinase-mediated DNA damage response in Toxoplasma gondii.","date":"2010","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20159970","citation_count":31,"is_preprint":false},{"pmid":"38524184","id":"PMC_38524184","title":"Toxoplasma gondii infection-induced host cellular DNA damage is strain-dependent and leads to the activation of the ATM-dependent homologous recombination pathway.","date":"2024","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/38524184","citation_count":4,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4013,"output_tokens":1871,"usd":0.020052,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7180,"output_tokens":2796,"usd":0.0529,"stage2_stop_reason":"end_turn"},"total_usd":0.072952,"stage1_batch_id":"msgbatch_01TEPNZ4MCzJ7xtsNwosiDRk","stage2_batch_id":"msgbatch_01FQShM7n1sfCr4pWTDShmki","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2009,\n      \"finding\": \"Toxoplasma gondii H2AX contains a complete SQ(E/D)φ motif (where φ denotes a hydrophobic residue) that is phosphorylated in response to DNA damage, whereas the canonical H2A1, which also has an SQ motif, lacks this complete motif and is not equivalently phosphorylated.\",\n      \"method\": \"Sequence analysis of SQ motif combined with detection of H2AX phosphorylation after DNA damage treatment\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct phosphorylation detected experimentally in the parasite with motif-level mechanistic explanation, single lab but two complementary approaches\",\n      \"pmids\": [\"19607843\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"A novel H2B variant (H2Bv) interacts with H2AZ and H2A1 but NOT with H2AX, indicating H2AX forms nucleosomes of distinct composition from the other H2A variants.\",\n      \"method\": \"Co-immunoprecipitation / interaction assay between H2A variants and H2Bv\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single-lab Co-IP result with explicit negative control for H2AX, single method\",\n      \"pmids\": [\"19607843\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"ChIP revealed that H2AX is enriched at repressed genes and at the silent TgIRE repeat element, while H2AZ is enriched at active genes, indicating H2AX marks transcriptionally silenced chromatin regions.\",\n      \"method\": \"Chromatin immunoprecipitation (ChIP)\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP directly maps genomic enrichment, single lab, single method\",\n      \"pmids\": [\"19607843\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"H2AX localizes to silenced chromatin areas during bradyzoite differentiation, and h2ax transcript levels increase in bradyzoites generated both in vitro and in vivo (G0-arrested), consistent with a role in chromatin silencing during stage conversion.\",\n      \"method\": \"Quantitative RT-PCR for transcript levels; localization by immunofluorescence/ChIP during bradyzoite differentiation\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — transcript and localization data across two differentiation conditions (in vitro and in vivo), single lab\",\n      \"pmids\": [\"19607843\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Overexpression of TgMYST-B (a MYST family lysine acetyltransferase) in Toxoplasma gondii leads to increased levels of phosphorylated H2AX, placing TgMYST-B upstream of H2AX phosphorylation in the DNA damage response pathway.\",\n      \"method\": \"Overexpression of recombinant tagged TgMYST-B with detection of phospho-H2AX levels; pharmacological inhibition of ATM kinase or KATs reverses associated phenotype\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic overexpression with pharmacological epistasis and quantified H2AX phosphorylation readout, single lab\",\n      \"pmids\": [\"20159970\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"The increase in phospho-H2AX upon TgMYST-B overexpression is dependent on ATM kinase activity, as pharmacological inhibition of ATM kinase reverses this effect, placing ATM kinase as the writer of H2AX phosphorylation in the T. gondii DNA damage response.\",\n      \"method\": \"ATM kinase pharmacological inhibition combined with phospho-H2AX level measurement in TgMYST-B-overexpressing parasites\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epistasis via pharmacological inhibitor with quantified phospho-H2AX readout, single lab\",\n      \"pmids\": [\"20159970\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"T. gondii infection of primary host endothelial cells induces DNA double-strand breaks in a strain-dependent manner, as quantified by γ-H2AX (phosphorylated H2AX) levels, with the RH strain driving the most prominent effect; this is accompanied by activation of the ATM-dependent homologous recombination pathway in host cells.\",\n      \"method\": \"γ-H2AX quantification by microscopy, comet assay, and measurement of HR/NHEJ pathway markers in T. gondii-infected primary endothelial cells\",\n      \"journal\": \"Frontiers in cellular and infection microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (comet assay, γ-H2AX quantification, pathway marker analysis) in a single lab; γ-H2AX used as a readout for host cell H2AX phosphorylation, not parasite H2AX\",\n      \"pmids\": [\"38524184\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}, {\"species\": \"Toxoplasma gondii\", \"strain\": \"Me49\"}, {\"species\": \"Toxoplasma gondii\", \"strain\": \"NED\"}]\n    }\n  ],\n  \"current_model\": \"Toxoplasma gondii H2AX bears a complete SQ(E/D)φ motif that is phosphorylated by ATM kinase in response to DNA damage (a process facilitated upstream by the MYST acetyltransferase TgMYST-B), associates with silenced and repressed chromatin regions (not active genes), forms compositionally distinct nucleosomes that exclude the H2Bv variant, and accumulates at silenced loci during bradyzoite differentiation, suggesting a dual role in the DNA damage response and chromatin-based transcriptional silencing.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"Toxoplasma gondii H2AX is a histone H2A variant that couples the DNA damage response to chromatin-based transcriptional silencing [#0, #2]. Unlike the canonical H2A1, which carries only a partial SQ motif, H2AX bears a complete SQ(E/D)\\u03c6 motif that is phosphorylated upon DNA damage [#0], and this phosphorylation is written by ATM kinase and promoted upstream by the MYST-family acetyltransferase TgMYST-B [#4, #5]. H2AX assembles into nucleosomes of distinct composition, being excluded from interaction with the H2Bv variant that partners H2AZ and H2A1 [#1]. Genome-wide, H2AX is enriched at repressed genes and the silent TgIRE repeat rather than active genes, and it accumulates at silenced chromatin during bradyzoite differentiation, when its transcript is upregulated [#2, #3]. Beyond these findings, the structural and biochemical details of how H2AX phosphorylation is coordinated with silencing have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"It was unknown whether T. gondii encodes a bona fide DNA-damage-responsive H2A variant; showing H2AX carries a complete SQ(E/D)\\u03c6 motif phosphorylated after DNA damage established it as the parasite's \\u03b3-H2AX equivalent and distinguished it from canonical H2A1.\",\n      \"evidence\": \"sequence analysis of the SQ motif plus detection of H2AX phosphorylation after DNA damage in the parasite\",\n      \"pmids\": [\"19607843\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not identify the kinase responsible\", \"Does not resolve the functional consequence of phosphorylation at damage sites\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Whether H2AX forms compositionally distinct nucleosomes was unresolved; demonstrating that the H2Bv variant partners H2AZ and H2A1 but not H2AX established that H2AX-containing nucleosomes are biochemically distinct from other H2A variant nucleosomes.\",\n      \"evidence\": \"Co-immunoprecipitation between H2A variants and H2Bv with H2AX as an explicit negative\",\n      \"pmids\": [\"19607843\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single Co-IP without reciprocal or reconstitution validation\", \"Does not define which H2B partners H2AX\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"The chromatin context of H2AX was unknown; ChIP mapping showed H2AX marks repressed genes and the silent TgIRE element while H2AZ marks active genes, and it accumulates at silenced loci with upregulated transcript during bradyzoite differentiation, establishing a role in transcriptional silencing and stage conversion.\",\n      \"evidence\": \"ChIP genomic mapping, quantitative RT-PCR, and localization during in vitro and in vivo bradyzoite differentiation\",\n      \"pmids\": [\"19607843\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not establish whether H2AX deposition is a cause or consequence of silencing\", \"Does not connect the silencing role to the DNA damage phosphorylation role\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"The writer and upstream regulator of H2AX phosphorylation were undefined; placing TgMYST-B upstream and ATM kinase as the writer established the signalling axis for H2AX phosphorylation in the parasite DNA damage response.\",\n      \"evidence\": \"TgMYST-B overexpression with phospho-H2AX readout and pharmacological ATM inhibition epistasis\",\n      \"pmids\": [\"20159970\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Relies on pharmacological inhibition rather than genetic ablation of ATM\", \"Does not define how TgMYST-B acetylation feeds into ATM activation\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"It was unclear whether infection perturbs host genome integrity; \\u03b3-H2AX quantification showed T. gondii induces host DNA double-strand breaks and ATM-dependent homologous recombination in a strain-dependent manner, with RH most potent.\",\n      \"evidence\": \"\\u03b3-H2AX microscopy, comet assay, and HR/NHEJ marker analysis in infected primary endothelial cells (host-cell H2AX readout)\",\n      \"pmids\": [\"38524184\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"\\u03b3-H2AX here reports host-cell, not parasite, H2AX\", \"Does not identify the parasite effector driving host DSBs\"],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"},\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"Me49\"},\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"NED\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the DNA-damage phosphorylation function of H2AX is mechanistically integrated with its role in transcriptional silencing, and the structural basis of its distinct nucleosome composition, remain open.\",\n      \"evidence\": \"no direct evidence in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of H2AX nucleosomes\", \"No genetic loss-of-function characterization of parasite H2AX\", \"Mechanistic link between silencing and DNA damage roles unresolved\"],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0031492\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0000790\", \"supporting_discovery_ids\": [2, 3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0000792\", \"supporting_discovery_ids\": [2, 3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006974\", \"supporting_discovery_ids\": [0, 4, 5], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0006342\", \"supporting_discovery_ids\": [2, 3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\n      \"H2AX-containing nucleosome (distinct composition, excludes H2Bv)\"\n    ],\n    \"partners\": [\n      \"ATM kinase (writer of H2AX phosphorylation)\",\n      \"TgMYST-B (upstream acetyltransferase promoting H2AX phosphorylation)\"\n    ],\n    \"other_free_text\": [\n      \"H2AX bears a complete SQ(E/D)\\u03c6 motif phosphorylated on DNA damage, unlike canonical H2A1 [#0]\",\n      \"H2Bv partners H2AZ and H2A1 but not H2AX [#1]\",\n      \"h2ax transcript upregulated during bradyzoite differentiation [#3]\",\n      \"\\u03b3-H2AX used as host-cell DSB readout during infection; parasite induces strain-dependent host DNA damage [#6]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_261580","name":null,"product":"histone H2AX","uniprot_acc":"A0A125YFR3","chromosome":"TGME49_chrVIIb","start_pos":1648939},{"strain":"GT1","gene_id":"TGGT1_261580","name":null,"product":"histone H2AX","uniprot_acc":null,"chromosome":"TGGT1_chrVIIb","start_pos":1624096},{"strain":"RH88","gene_id":"TGRH88_069130","name":null,"product":"histone H2AX","uniprot_acc":null,"chromosome":"CM023089","start_pos":1668910},{"strain":"VEG","gene_id":"TGVEG_261580","name":null,"product":"histone H2AX","uniprot_acc":"A0A0F7UVP8","chromosome":"TGVEG_chrVIIb","start_pos":1664780}]}