Franziska Bleichert, PhD
Assistant ProfessorCards
Appointments
Contact Info
About
Copy Link
Titles
Assistant Professor
Biography
Dr. Bleichert’s research focuses on understanding the operating principles of macromolecular machines involved in chromosome replication and in the maintenance of genome stability using a combination of structural biology, biochemical, biophysical, and cellular approaches. She obtained her PhD from Yale University in 2010 working on ribosome biogenesis, and afterwards performed her postdoctoral work at UC Berkeley as a Miller Fellow, and then at Johns Hopkins Medical School. As a postdoctoral fellow, she determined the structure of the eukaryotic initiator complex, a key component in the assembly pathway of the DNA replication machinery. Since 2017, Dr. Bleichert has been an independent research group leader at the Friedrich Miescher Institute for Biomedical Research in Basel, Switzerland. She will join Yale’s Department of Molecular Biophysics and Biochemistry as an Assistant Professor in January 2020.
Appointments
Molecular Biophysics and Biochemistry
Assistant ProfessorPrimary
Other Departments & Organizations
- All Institutions
- Biochemistry, Quantitative Biology, Biophysics and Structural Biology (BQBS)
- DNA Damage and Genome Integrity
- Molecular Biophysics and Biochemistry
- Molecular Medicine, Pharmacology, and Physiology
- Plant Molecular Biology
- Yale Cancer Center
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
Education & Training
- Junior Group Leader
- Friedrich Miescher Institute for Biomedical Research (Switzerland) (2019)
- Postdoctoral Fellow
- Johns Hopkins School of Medicine (2016)
- Miller Fellow
- University of California, Berkeley (2013)
- MD (equiv.)
- University of Leipzig, School of Medicine (Germany) (2010)
- PhD
- Yale University
Research
Copy Link
Overview
Medical Research Interests
ORCID
0000-0003-0014-770X- View Lab Website
Bleichert lab
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Ashish Kumar, PhD
Adam Krysztofiak, PhD
Daniel Andrés Colón-Ríos
Faye Rogers, PhD
Lilian Kabeche, PhD
Peter M. Glazer, MD, PhD
DNA Replication
Publications
2025
Molecular impacts of Meier–Gorlin syndrome mutations on human origin licensing
Yang R, Hunker O, Kim J, Bleichert F. Molecular impacts of Meier–Gorlin syndrome mutations on human origin licensing. Journal Of Biological Chemistry 2025, 302: 111100. PMID: 41448435, PMCID: PMC12830165, DOI: 10.1016/j.jbc.2025.111100.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsMeier-Gorlin syndrome mutationsOrigin recognition complexMeier-Gorlin syndromeOrigin licensingDNA replication initiation factorMolecular basisCore domainATP-dependent DNA bindingReplication initiation factorsMolecular impactMCM subunitsRecognition complexDisease mutationsInitiation factorsDNA bindingOrigin licensing factorsLicensing factorMissense mutationsDouble hexamersMutationsDNAPrimordial dwarfismSyndrome mutationsCdt1Cdc6License to Replicate: Mechanisms of Licensing Eukaryotic Origins for DNA Replication
Frisbie V, Bleichert F. License to Replicate: Mechanisms of Licensing Eukaryotic Origins for DNA Replication. BioEssays 2025, 48: e70095. PMID: 41423967, PMCID: PMC12719912, DOI: 10.1002/bies.70095.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsDNA replicationOrigin licensingYeast model systemReplication initiation eventsGenomic DNA replicationBudding YeastHigher eukaryotesEukaryotic originBiochemical reconstitutionGenome replicationOrigin DNAHuman proteinsOrigin firingHelicase motorEukaryotesDNAYeastCell proliferationLiving organismsReplicationModel systemInitial eventMetazoaGenomeStructural detailsAlphaFold-guided phylogenetic analyses suggest surprising heterogeneity in metazoan replication origin licensing mechanisms
Hunker O, Bleichert F. AlphaFold-guided phylogenetic analyses suggest surprising heterogeneity in metazoan replication origin licensing mechanisms. The EMBO Journal 2025, 45: 310-333. PMID: 41310087, PMCID: PMC12759066, DOI: 10.1038/s44318-025-00628-5.Peer-Reviewed Original ResearchCitationsAltmetricConceptsOrigin recognition complexSubunits of origin recognition complexPhysiological relevanceDNA replication initiationExperimentally testable hypothesesMetazoan lineagesProtein evolutionEvolutionary conservationPhylogenetic approachReplication initiationMetazoan speciesPhylogenetic analysisReplication originsRecognition complexReplication machineryMCM loadingHelicase motorOrigin licensingOrc3Tethering interactionsTestable hypothesesSpeciesAlphaFoldMetazoaOrc6The mitotic ATR-Chk1 pathway promotes CDK1 activity for faithful chromosome segregation
Joo Y, Parrado C, Li W, Yang R, Black E, Bleichert F, Liu Y, Kabeche L. The mitotic ATR-Chk1 pathway promotes CDK1 activity for faithful chromosome segregation. Cell Reports 2025, 44: 116019. PMID: 40705605, PMCID: PMC12451630, DOI: 10.1016/j.celrep.2025.116019.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsDNA damage responseCdk1 activityATR-Chk1 pathwayChromosome segregationATR-Chk1Aurora B activityResidual activityCheckpoint kinase 1Mitotic progressionCDK1 inhibitionDamage responseRad3-relatedCDK1Lagging chromosomesATR-Chk1 activationHuman cellsChromosomeKinase 1Ataxia telangiectasiaMitosisChk1DNA damageDNAB activityPartial loss
2024
Multiple mechanisms for licensing human replication origins
Yang R, Hunker O, Wise M, Bleichert F. Multiple mechanisms for licensing human replication origins. Nature 2024, 636: 488-498. PMID: 39604729, PMCID: PMC11910750, DOI: 10.1038/s41586-024-08237-8.Peer-Reviewed Original ResearchCitationsAltmetricConceptsOrigin recognition complexReplication originsMCM loadingHexamer formationDNA replication initiationDNA replication machineryHuman replication originsOrc6 subunitMulticellular eukaryotesBiochemical reconstitutionReplication initiationRecognition complexReplicative helicaseMultiple mechanismsReplication machineryEukaryotic MCM2Helicase motorReplication stressOrigin licensingDimer interfaceOrc6Reconstituted systemYeastHexamerMCM2Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition
Rackear M, Quijano E, Ianniello Z, Colón-Ríos D, Krysztofiak A, Abdullah R, Liu Y, Rogers F, Ludwig D, Dwivedi R, Bleichert F, Glazer P. Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition. Oncotarget 2024, 15: 699-713. PMID: 39352803, PMCID: PMC11444335, DOI: 10.18632/oncotarget.28651.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsTumor targetingMonoclonal antibody therapyTumor-specific targetingCell uptakeNucleic acid bindingCell surface antigensAntibody therapyHuman variantsClinical successCell-penetrating antibodiesAcid bindingSystemic administrationSurface antigensTumorRAD51 inhibitionAntibody platformMechanism of cell penetrationBind RAD51AntibodiesFull-lengthSpecific targetsCell penetrationDisease targetsCellsAutoantibodies
2023
A dual role for the chromatin reader ORCA/LRWD1 in targeting the origin recognition complex to chromatin
Sahu S, Ekundayo B, Kumar A, Bleichert F. A dual role for the chromatin reader ORCA/LRWD1 in targeting the origin recognition complex to chromatin. The EMBO Journal 2023, 42: embj2023114654. PMID: 37551430, PMCID: PMC10505921, DOI: 10.15252/embj.2023114654.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsOrigin recognition complexH4K20 trimethylationHeterochromatin replicationRecognition complexCryo-electron microscopy structureLocal chromatin environmentSpecific histone marksSpecific chromatin contextsMcm2-7 loadingTernary complex assemblyChromatin environmentChromatin marksChromatin contextHistone marksHistone modificationsReplication initiationEukaryotic cellsMicroscopy structureChromatin condensatesORC recruitmentDNA replicationMammalian cellsNucleosomal DNAAromatic cageComplex assembly
2022
A mechanism of origin licensing control through autoinhibition of S. cerevisiae ORC·DNA·Cdc6
Schmidt JM, Yang R, Kumar A, Hunker O, Seebacher J, Bleichert F. A mechanism of origin licensing control through autoinhibition of S. cerevisiae ORC·DNA·Cdc6. Nature Communications 2022, 13: 1059. PMID: 35217664, PMCID: PMC8881611, DOI: 10.1038/s41467-022-28695-w.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsOrigin recognition complexS. cerevisiaeCyclin-dependent kinase phosphorylationMcm2-7 loadingN-terminal domainCryo-electron microscopyCDK phosphorylationRecognition complexDNA replicationReplication originsÅ resolutionKinase phosphorylationMechanism of originCdc6Coordinated actionCerevisiaePhosphorylationDNAInhibitory signalsStructural detailsSite regulationRecruitmentOrc6AssemblyCdt1
2020
Structural mechanism for replication origin binding and remodeling by a metazoan origin recognition complex and its co-loader Cdc6
Schmidt JM, Bleichert F. Structural mechanism for replication origin binding and remodeling by a metazoan origin recognition complex and its co-loader Cdc6. Nature Communications 2020, 11: 4263. PMID: 32848132, PMCID: PMC7450096, DOI: 10.1038/s41467-020-18067-7.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsAAA DomainAdenosine TriphosphateAnimalsCell Cycle ProteinsCryoelectron MicroscopyDNADrosophila melanogasterDrosophila ProteinsHydrolysisMinichromosome Maintenance ProteinsModels, MolecularOrigin Recognition ComplexProtein BindingRecombinant ProteinsReplication OriginSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsConceptsOrigin recognition complexRecognition complexReplication originsDrosophila origin recognition complexEukaryotic DNA replication initiationMetazoan origin recognition complexCryo-electron microscopy structureMcm2-7 replicative helicaseATPase siteDNA replication initiationWalker B motifMcm2-7 loadingWinged-helix domainReplicative helicaseReplication initiationMicroscopy structureDistinct DNAB motifOrigin recognitionDNA sequencesDNA bendingDNA bindingPrimary DNADNA geometryLoop region
2019
Mechanisms of replication origin licensing: a structural perspective
Bleichert F. Mechanisms of replication origin licensing: a structural perspective. Current Opinion In Structural Biology 2019, 59: 195-204. PMID: 31630057, DOI: 10.1016/j.sbi.2019.08.007.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCitationsMeSH Keywords and ConceptsConceptsReplicative helicasesKey cell cycle eventsReplication origin licensingReplication start sitesCell cycle eventsOrigin licensingReplicative helicaseReplication initiationInitiation factorsStart siteChromosomal DNAReplicative machineryCycle eventsMolecular approachesSynthesis apparatusHelicasesMachineryStructural perspectiveBidirectional mannerDNAEukaryotesHelicaseRecent advancesDuplicationMechanism
Academic Achievements & Community Involvement
Copy Link
Honors
honor ERC Starting Grant
10/01/2017International AwardDetailsSwitzerlandhonor Miller Research Fellowship
07/01/2010Other AwardDetailsUnited Stateshonor Stanford Biochemistry Founders’ Award for Doctoral Excellence
05/01/2010National AwardDetailsUnited Stateshonor Boehringer Ingelheim Fonds PhD Fellowship
01/01/2005International AwardDetailsGermany
News
Copy Link
Get In Touch
Copy Link
Contacts
Locations
Yale Science Building
Academic Office
260 Whitney Avenue, Fl 3, Rm 345
New Haven, CT 06511