{"gene":"PF3D7_0904800","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2013,"finding":"PfRPA1S (PF3D7_0904800, the small fragment RPA1 homologue) negatively regulates the function of PfRPA1L in a dose-dependent manner during PfRad51-mediated homologous pairing and strand exchange activity in vitro.","method":"In vitro DNA strand exchange and homologous pairing assays with recombinant proteins; dose-dependent inhibition of PfRPA1L activity by addition of PfRPA1S","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro biochemical reconstitution with recombinant proteins, single lab, single study","pmids":["23631919"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"PfRPA1S (PF3D7_0904800) transcript and protein levels are upregulated in response to methyl methane sulfonate-induced DNA damage in P. falciparum parasites, indicating a physiological role in the DNA damage response.","method":"Comet assay for DNA damage assessment; transcript and protein level measurement by RT-PCR and western blot following MMS treatment","journal":"mBio","confidence":"Low","confidence_rationale":"Tier 3 / Weak — expression-level upregulation measured in a single lab, single study, without direct functional epistasis or mechanistic pathway placement for PF3D7_0904800 specifically","pmids":["23631919"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0904800 (PfRPA1S, the small-fragment replication protein A1 homologue in P. falciparum) acts as a negative regulator of PfRPA1L-stimulated, PfRad51-mediated homologous DNA strand exchange in a dose-dependent manner in vitro, and its transcript and protein are upregulated upon DNA damage, suggesting a modulatory role in homologous recombination and DNA repair."},"narrative":{"mechanistic_narrative":"PF3D7_0904800 (the small-fragment replication protein A1 homologue of Plasmodium falciparum) functions as a negative modulator of homologous recombination in vitro: added in a dose-dependent manner, it suppresses the PfRPA1L-stimulated, PfRad51-mediated homologous pairing and DNA strand exchange reaction [PMID:23631919]. Its transcript and protein levels rise following methyl methane sulfonate-induced DNA damage, consistent with participation in the parasite DNA damage response [PMID:23631919]. Beyond these two observations from a single study, no further mechanistic detail — including its physical interaction interface with PfRPA1L, in vivo epistasis, or structural basis of regulation — has been characterized in the available corpus.","teleology":[{"year":2013,"claim":"To determine whether the small-fragment RPA1 homologue plays a role in recombination, its effect on the core strand-exchange machinery was tested, establishing it as a dose-dependent negative regulator of PfRPA1L-stimulated, PfRad51-mediated homologous pairing.","evidence":"In vitro DNA strand exchange and homologous pairing assays with recombinant proteins, titrating PfRPA1S against PfRPA1L activity","pmids":["23631919"],"confidence":"Medium","gaps":["The physical basis of inhibition (direct binding to PfRPA1L, competition for DNA, or another mechanism) is not defined","No in vivo genetic epistasis confirms this regulatory role in living parasites","Whether the effect is specific to Rad51-mediated exchange or generalizes to other recombination reactions is untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"To connect the biochemical activity to a physiological trigger, expression was measured after genotoxic stress, showing that PF3D7_0904800 transcript and protein are induced by DNA damage and implicating it in the parasite DNA damage response.","evidence":"Comet assay to confirm DNA damage plus RT-PCR and western blot of PfRPA1S levels after methyl methane sulfonate treatment of P. falciparum","pmids":["23631919"],"confidence":"Low","gaps":["Expression-level upregulation was measured in a single study without functional epistasis placing PF3D7_0904800 in a specific repair pathway","The signalling route linking DNA damage to induction is unknown","Whether induced protein exerts the same inhibitory effect in vivo as observed in vitro is not shown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How PF3D7_0904800 integrates with the full RPA complex and homologous recombination machinery in living parasites, and the structural/mechanistic basis of its regulatory action, remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No in vivo knockout, knockdown, or complementation data for PF3D7_0904800","No structural model or defined interaction interface with PfRPA1L or DNA","No demonstration of a repair or replication phenotype attributable to PF3D7_0904800"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFRPA1L (FUNCTIONAL ANTAGONISM IN VITRO)","PFRAD51 (ACTIVITY MODULATED IN STRAND-EXCHANGE REACTION)"],"other_free_text":["Acts as a dose-dependent negative regulator of PfRPA1L-stimulated, PfRad51-mediated homologous pairing and strand exchange in vitro [#0]","Transcript and protein upregulated in response to MMS-induced DNA damage [#1]","All evidence derives from a single 2013 study; no in vivo genetic characterization of PF3D7_0904800 exists in the corpus"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"23631919","id":"PMC_23631919","title":"Opposing roles for two molecular forms of replication protein A in Rad51-Rad54-mediated DNA recombination in Plasmodium falciparum.","date":"2013","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/23631919","citation_count":26,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3600,"output_tokens":623,"usd":0.010072,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5193,"output_tokens":1677,"usd":0.033945,"stage2_stop_reason":"end_turn"},"total_usd":0.044017,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2013,\n      \"finding\": \"PfRPA1S (PF3D7_0904800, the small fragment RPA1 homologue) negatively regulates the function of PfRPA1L in a dose-dependent manner during PfRad51-mediated homologous pairing and strand exchange activity in vitro.\",\n      \"method\": \"In vitro DNA strand exchange and homologous pairing assays with recombinant proteins; dose-dependent inhibition of PfRPA1L activity by addition of PfRPA1S\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro biochemical reconstitution with recombinant proteins, single lab, single study\",\n      \"pmids\": [\"23631919\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"PfRPA1S (PF3D7_0904800) transcript and protein levels are upregulated in response to methyl methane sulfonate-induced DNA damage in P. falciparum parasites, indicating a physiological role in the DNA damage response.\",\n      \"method\": \"Comet assay for DNA damage assessment; transcript and protein level measurement by RT-PCR and western blot following MMS treatment\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — expression-level upregulation measured in a single lab, single study, without direct functional epistasis or mechanistic pathway placement for PF3D7_0904800 specifically\",\n      \"pmids\": [\"23631919\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0904800 (PfRPA1S, the small-fragment replication protein A1 homologue in P. falciparum) acts as a negative regulator of PfRPA1L-stimulated, PfRad51-mediated homologous DNA strand exchange in a dose-dependent manner in vitro, and its transcript and protein are upregulated upon DNA damage, suggesting a modulatory role in homologous recombination and DNA repair.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0904800 (the small-fragment replication protein A1 homologue of Plasmodium falciparum) functions as a negative modulator of homologous recombination in vitro: added in a dose-dependent manner, it suppresses the PfRPA1L-stimulated, PfRad51-mediated homologous pairing and DNA strand exchange reaction [#0]. Its transcript and protein levels rise following methyl methane sulfonate-induced DNA damage, consistent with participation in the parasite DNA damage response [#1]. Beyond these two observations from a single study, no further mechanistic detail — including its physical interaction interface with PfRPA1L, in vivo epistasis, or structural basis of regulation — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"To determine whether the small-fragment RPA1 homologue plays a role in recombination, its effect on the core strand-exchange machinery was tested, establishing it as a dose-dependent negative regulator of PfRPA1L-stimulated, PfRad51-mediated homologous pairing.\",\n      \"evidence\": \"In vitro DNA strand exchange and homologous pairing assays with recombinant proteins, titrating PfRPA1S against PfRPA1L activity\",\n      \"pmids\": [\n        \"23631919\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The physical basis of inhibition (direct binding to PfRPA1L, competition for DNA, or another mechanism) is not defined\",\n        \"No in vivo genetic epistasis confirms this regulatory role in living parasites\",\n        \"Whether the effect is specific to Rad51-mediated exchange or generalizes to other recombination reactions is untested\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"To connect the biochemical activity to a physiological trigger, expression was measured after genotoxic stress, showing that PF3D7_0904800 transcript and protein are induced by DNA damage and implicating it in the parasite DNA damage response.\",\n      \"evidence\": \"Comet assay to confirm DNA damage plus RT-PCR and western blot of PfRPA1S levels after methyl methane sulfonate treatment of P. falciparum\",\n      \"pmids\": [\n        \"23631919\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Expression-level upregulation was measured in a single study without functional epistasis placing PF3D7_0904800 in a specific repair pathway\",\n        \"The signalling route linking DNA damage to induction is unknown\",\n        \"Whether induced protein exerts the same inhibitory effect in vivo as observed in vitro is not shown\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PF3D7_0904800 integrates with the full RPA complex and homologous recombination machinery in living parasites, and the structural/mechanistic basis of its regulatory action, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No in vivo knockout, knockdown, or complementation data for PF3D7_0904800\",\n        \"No structural model or defined interaction interface with PfRPA1L or DNA\",\n        \"No demonstration of a repair or replication phenotype attributable to PF3D7_0904800\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0140664\",\n        \"supporting_discovery_ids\": [0]\n      }\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0035825\",\n        \"supporting_discovery_ids\": [0]\n      },\n      {\n        \"term_id\": \"GO:0006974\",\n        \"supporting_discovery_ids\": [1]\n      }\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PfRPA1L (functional antagonism in vitro)\",\n      \"PfRad51 (activity modulated in strand-exchange reaction)\"\n    ],\n    \"other_free_text\": [\n      \"Acts as a dose-dependent negative regulator of PfRPA1L-stimulated, PfRad51-mediated homologous pairing and strand exchange in vitro [#0]\",\n      \"Transcript and protein upregulated in response to MMS-induced DNA damage [#1]\",\n      \"All evidence derives from a single 2013 study; no in vivo genetic characterization of PF3D7_0904800 exists in the corpus\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0904800","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 1 cited papers name other catalogue genes (PF3D7_0409600, PF3D7_0508800, PF3D7_0803400). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0904800","name":null,"product":"replication protein A1, small fragment","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0416600","name":null,"product":"replication protein A1, small fragment","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0702500","name":null,"product":"replication protein A1, small fragment","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}