grant
Topologically complex DNA substrates to aid structure determination of the human topoisomerase IIa
Organization JOHNS HOPKINS UNIVERSITYLocation BALTIMORE, UNITED STATESPosted 3 Jul 2025Deadline 2 Jul 2028
NIHUS FederalResearch GrantFY2025170 kD DNA Topoisomerase IIAddressAlpha Isozyme DNA Topoisomerase IIAnti-Cancer AgentsAntineoplastic AgentsAntineoplastic DrugsAntineoplasticsArtifactsAssayBindingBioassayBiologic ModelsBiological AssayBiological ModelsBiologyC-terminalCancer DrugCancer TreatmentCell BodyCell DeathCell Growth in NumberCell MultiplicationCell ProliferationCellsCellular ProliferationChromatinChromosomesClinicalCollaborationsComplexCryo-electron MicroscopyCryoelectron MicroscopyCrystallizationCrystallographiesCrystallographyDNADNA DamageDNA Double Strand BreakDNA InjuryDNA ReplicationDNA SynthesisDNA Topoisomerase IIDNA Type 2 TopoisomeraseDNA biosynthesisDNA lesionDNA topoisomerase II alphaDNA topoisomerase II αDeoxyribonucleic AcidDiseaseDisorderDrugsEPEGElectron CryomicroscopyElementsEnzyme GeneEnzymesEposideEtoposideEventFamilyFluorescence PolarizationGelGene TranscriptionGenetic TranscriptionGenome InstabilityGenome StabilityGenomic InstabilityGenomic StabilityHumanImageKnowledgeLastetLeftLengthLesionLytotoxicityMalignant CellMalignant Neoplasm TherapyMalignant Neoplasm TreatmentMediatingMedicationMethodsModel SystemModern ManMolecular ConfigurationMolecular ConformationMolecular InteractionMolecular StereochemistryMorphologic artifactsNeoplastic Disease Chemotherapeutic AgentsNeurofibrillary TanglesNucleosomesOutcomePharmaceutical PreparationsPhysiologicPhysiologicalPoisonProcessPropertyRNA ExpressionReactionReportingResearchRoleStructureSupercoiled DNASuperhelical DNASupertwisted DNATOP2A gene productTherapeutic InterventionTimeTopo IITopo II AlphaTopo II αTopoIIaTopoisomeraseTopoisomerase IITopoisomerase II AlphaTopoisomerase IIαTopoisomerase InteractionToxic ChemicalToxic SubstanceTranscriptionTumor-Specific Treatment AgentsType II DNA TopoisomerasesVepesidVisualizationWorkanti-cancer druganti-cancer therapybiophysical analysisbiophysical studiescancer cellcancer therapycancer-directed therapychemotherapeutic agentchemotherapeutic compoundschemotherapeutic drugschemotherapeutic medicationsconformationconformationalconformational stateconformationallyconformationscryo-EMcryoEMcryogenic electron microscopycytotoxiccytotoxicitydesigndesigningdrug/agentgenome integritygenomic integrityimagingin vivoinsightintervention therapymutantnecrocytosisneurofibrillary degenerationneurofibrillary lesionneurofibrillary pathologynovelprospectivereconstitutereconstitutionrecruitrepairrepairedsingle moleculesocial roletangletopoisomerase IIatoxic compound
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Project Summary/Abstract
Type II topoisomerases (TOP2s) are essenƟal enzymes that maintain DNA topology using an ATP-dependent “strand-
passage” mechanism that physically moves one DNA segment through a transient, enzyme-mediated double-stranded
break in another. Under normal condiƟons, TOP2s perform strand passage to facilitate fundamental…
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