{"gene":"PF3D7_0803400","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2013,"finding":"PF3D7_0803400 (PfRad54) accelerates PfRad51-mediated pairing between single-stranded DNA (ssDNA) and its homologous linear double-stranded DNA (dsDNA) in vitro in the presence of 0.5 mM CaCl2, establishing RAD54 as a functional stimulator of Rad51-dependent homologous strand exchange in P. falciparum.","method":"In vitro DNA strand exchange/pairing assay using recombinant proteins; comet assay for in vivo DNA damage; transcript and protein level analysis (upregulation upon MMS-induced DNA damage)","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct in vitro biochemical assay with recombinant PfRad54 and PfRad51, corroborated by in vivo comet assay and expression data, but from a single lab and single publication","pmids":["23631919"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"PF3D7_0803400 (RAD54) transcript is upregulated in P. falciparum in response to MMS-induced DNA damage, consistent with its participation in the double-strand break repair system; additionally, mutator strains Dd2 and W2 fail to induce DNA repair gene expression upon MMS treatment, and genome sequencing identified point mutations in 18 DNA repair genes in these strains (RAD54 included among the broader repair gene set examined).","method":"Genome-wide transcriptional profiling (microarray/RNA-seq) after MMS treatment; genome sequencing of mutator strains","journal":"Scientific reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — transcriptional evidence only, no direct biochemical assay on RAD54 protein itself; single lab, genome-wide study in which RAD54 is one of many genes","pmids":["27033103"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"},{"species":"Plasmodium falciparum","strain":"Dd2"},{"species":"Plasmodium falciparum","strain":"W2"}]}],"current_model":"PF3D7_0803400 (RAD54) functions as a stimulator of PfRad51-mediated homologous recombination in P. falciparum, directly accelerating Rad51-driven ssDNA–dsDNA pairing in vitro, and its transcript is upregulated in response to DNA damage, placing it in the parasite's double-strand break repair pathway."},"narrative":{"mechanistic_narrative":"PF3D7_0803400 (RAD54) is a stimulator of Rad51-mediated homologous recombination in the double-strand break repair pathway of Plasmodium falciparum [PMID:23631919]. In vitro, recombinant PF3D7_0803400 accelerates PfRad51-driven pairing between single-stranded DNA and its homologous linear double-stranded DNA in the presence of 0.5 mM CaCl2, establishing it as a functional accelerant of Rad51-dependent strand exchange [PMID:23631919]. Consistent with a DNA repair role, its transcript is upregulated following MMS-induced DNA damage [PMID:23631919, PMID:27033103]. Beyond this stimulatory activity in Rad51-mediated strand exchange and its damage-responsive expression, no further mechanistic detail for PF3D7_0803400 has been characterized in the available corpus.","teleology":[{"year":2013,"claim":"Whether P. falciparum encodes a functional Rad54-type factor capable of promoting Rad51-dependent recombination was unresolved; this work showed the gene product directly accelerates Rad51-mediated homologous strand pairing.","evidence":"In vitro DNA strand exchange/pairing assay with recombinant PfRad54 and PfRad51, plus comet assay and expression analysis after MMS damage","pmids":["23631919"],"confidence":"Medium","gaps":["Single lab and single publication; no reciprocal or independent biochemical confirmation","No structural model or ATPase/translocase characterization of the protein reported","In vivo requirement of RAD54 for recombination or repair not tested by genetic knockout"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"claim":"Whether RAD54 expression is coupled to the parasite's DNA damage response was addressed by profiling transcription after MMS treatment, placing the gene within the induced double-strand break repair program.","evidence":"Genome-wide transcriptional profiling after MMS treatment and genome sequencing of mutator strains","pmids":["27033103"],"confidence":"Low","gaps":["Transcriptional evidence only; no direct assay on RAD54 protein and RAD54 is one of many genes profiled","Functional consequence of the damage-induced upregulation for RAD54 specifically not established","Point mutations were catalogued across DNA repair genes broadly, not shown to affect RAD54 function"],"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"},{"species":"Plasmodium falciparum","strain":"Dd2"},{"species":"Plasmodium falciparum","strain":"W2"}]},{"year":null,"claim":"Whether PF3D7_0803400 is genetically required for homologous recombination or DSB repair in vivo, and the biochemical basis of its stimulatory activity, remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No genetic loss-of-function analysis of RAD54 in the parasite","No structural or enzymatic (e.g. ATP-dependent) characterization in the corpus","Interaction with Rad51 shown functionally in vitro but not mapped or validated by independent methods"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFRAD51"],"other_free_text":["PF3D7_0803400 (RAD54) accelerates PfRad51-mediated ssDNA-dsDNA pairing in vitro in the presence of 0.5 mM CaCl2 [#0].","RAD54 transcript is upregulated upon MMS-induced DNA damage in P. falciparum [#0, #1].","No genetic knockout, structural, or enzymatic mechanistic data for PF3D7_0803400 is present in the corpus."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"3088783","id":"PMC_3088783","title":"Rapid repeated DNA replication during microgametogenesis and DNA synthesis in young zygotes of Plasmodium berghei.","date":"1986","source":"Transactions of the Royal Society of Tropical Medicine and Hygiene","url":"https://pubmed.ncbi.nlm.nih.gov/3088783","citation_count":61,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"2440713","id":"PMC_2440713","title":"Plasmodium species: flow cytometry and microfluorometry assessments of DNA content and synthesis.","date":"1987","source":"Experimental parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/2440713","citation_count":57,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27033103","id":"PMC_27033103","title":"DNA damage regulation and its role in drug-related phenotypes in the malaria parasites.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/27033103","citation_count":56,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"4971014","id":"PMC_4971014","title":"DNA, RNA , and protein synthesis in erythrocytic forms of Plasmodium knowlesi.","date":"1968","source":"The American journal of tropical medicine and hygiene","url":"https://pubmed.ncbi.nlm.nih.gov/4971014","citation_count":56,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"87413","id":"PMC_87413","title":"Plasmodium-infected blood cells analyzed and sorted by flow fluorimetry with the deoxyribonucleic acid binding dye 33258 Hoechst.","date":"1979","source":"The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society","url":"https://pubmed.ncbi.nlm.nih.gov/87413","citation_count":52,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"3283664","id":"PMC_3283664","title":"DNA synthesis in gametocytes of Plasmodium falciparum.","date":"1988","source":"Parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/3283664","citation_count":47,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15948708","id":"PMC_15948708","title":"DNA-[adenine] methylation in lower eukaryotes.","date":"2005","source":"Biochemistry. Biokhimiia","url":"https://pubmed.ncbi.nlm.nih.gov/15948708","citation_count":42,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"2892060","id":"PMC_2892060","title":"From Laveran's discovery to DNA probes: new trends in diagnosis of malaria.","date":"1987","source":"Lancet (London, England)","url":"https://pubmed.ncbi.nlm.nih.gov/2892060","citation_count":31,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"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":27,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAD54","PfRAD54"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39950472","id":"PMC_39950472","title":"A Potential Regulatory Network of Selected Human Erythrocytic miRNAs with Plasmodium falciparum 3D7 mRNAs: A Computational Analysis.","date":"2025","source":"MicroRNA (Shariqah, United Arab Emirates)","url":"https://pubmed.ncbi.nlm.nih.gov/39950472","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAD54"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6548,"output_tokens":773,"usd":0.015619,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5417,"output_tokens":1632,"usd":0.033943,"stage2_stop_reason":"end_turn"},"total_usd":0.049562,"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\": \"PF3D7_0803400 (PfRad54) accelerates PfRad51-mediated pairing between single-stranded DNA (ssDNA) and its homologous linear double-stranded DNA (dsDNA) in vitro in the presence of 0.5 mM CaCl2, establishing RAD54 as a functional stimulator of Rad51-dependent homologous strand exchange in P. falciparum.\",\n      \"method\": \"In vitro DNA strand exchange/pairing assay using recombinant proteins; comet assay for in vivo DNA damage; transcript and protein level analysis (upregulation upon MMS-induced DNA damage)\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct in vitro biochemical assay with recombinant PfRad54 and PfRad51, corroborated by in vivo comet assay and expression data, but from a single lab and single publication\",\n      \"pmids\": [\"23631919\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"PF3D7_0803400 (RAD54) transcript is upregulated in P. falciparum in response to MMS-induced DNA damage, consistent with its participation in the double-strand break repair system; additionally, mutator strains Dd2 and W2 fail to induce DNA repair gene expression upon MMS treatment, and genome sequencing identified point mutations in 18 DNA repair genes in these strains (RAD54 included among the broader repair gene set examined).\",\n      \"method\": \"Genome-wide transcriptional profiling (microarray/RNA-seq) after MMS treatment; genome sequencing of mutator strains\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — transcriptional evidence only, no direct biochemical assay on RAD54 protein itself; single lab, genome-wide study in which RAD54 is one of many genes\",\n      \"pmids\": [\"27033103\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"Dd2\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"W2\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0803400 (RAD54) functions as a stimulator of PfRad51-mediated homologous recombination in P. falciparum, directly accelerating Rad51-driven ssDNA–dsDNA pairing in vitro, and its transcript is upregulated in response to DNA damage, placing it in the parasite's double-strand break repair pathway.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0803400 (RAD54) is a stimulator of Rad51-mediated homologous recombination in the double-strand break repair pathway of Plasmodium falciparum [#0]. In vitro, recombinant PF3D7_0803400 accelerates PfRad51-driven pairing between single-stranded DNA and its homologous linear double-stranded DNA in the presence of 0.5 mM CaCl2, establishing it as a functional accelerant of Rad51-dependent strand exchange [#0]. Consistent with a DNA repair role, its transcript is upregulated following MMS-induced DNA damage [#0, #1]. Beyond this stimulatory activity in Rad51-mediated strand exchange and its damage-responsive expression, no further mechanistic detail for PF3D7_0803400 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Whether P. falciparum encodes a functional Rad54-type factor capable of promoting Rad51-dependent recombination was unresolved; this work showed the gene product directly accelerates Rad51-mediated homologous strand pairing.\",\n      \"evidence\": \"In vitro DNA strand exchange/pairing assay with recombinant PfRad54 and PfRad51, plus comet assay and expression analysis after MMS damage\",\n      \"pmids\": [\"23631919\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Single lab and single publication; no reciprocal or independent biochemical confirmation\",\n        \"No structural model or ATPase/translocase characterization of the protein reported\",\n        \"In vivo requirement of RAD54 for recombination or repair not tested by genetic knockout\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Whether RAD54 expression is coupled to the parasite's DNA damage response was addressed by profiling transcription after MMS treatment, placing the gene within the induced double-strand break repair program.\",\n      \"evidence\": \"Genome-wide transcriptional profiling after MMS treatment and genome sequencing of mutator strains\",\n      \"pmids\": [\"27033103\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Transcriptional evidence only; no direct assay on RAD54 protein and RAD54 is one of many genes profiled\",\n        \"Functional consequence of the damage-induced upregulation for RAD54 specifically not established\",\n        \"Point mutations were catalogued across DNA repair genes broadly, not shown to affect RAD54 function\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"Dd2\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"W2\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PF3D7_0803400 is genetically required for homologous recombination or DSB repair in vivo, and the biochemical basis of its stimulatory activity, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No genetic loss-of-function analysis of RAD54 in the parasite\",\n        \"No structural or enzymatic (e.g. ATP-dependent) characterization in the corpus\",\n        \"Interaction with Rad51 shown functionally in vitro but not mapped or validated by independent methods\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0000724\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006302\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PfRad51\"],\n    \"other_free_text\": [\n      \"PF3D7_0803400 (RAD54) accelerates PfRad51-mediated ssDNA-dsDNA pairing in vitro in the presence of 0.5 mM CaCl2 [#0].\",\n      \"RAD54 transcript is upregulated upon MMS-induced DNA damage in P. falciparum [#0, #1].\",\n      \"No genetic knockout, structural, or enzymatic mechanistic data for PF3D7_0803400 is present in the corpus.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0803400","name":null,"product":"DNA repair and recombination protein RAD54, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1226800","name":null,"product":"DNA repair and recombination protein RAD54, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0115500","name":null,"product":"DNA repair and recombination protein RAD54, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RAD54","evaluation":null}