Franziska Bleichert, PhD
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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
- Biochemistry, Quantitative Biology, Biophysics and Structural Biology (BQBS)
- Molecular Biophysics and Biochemistry
- Molecular Medicine, Pharmacology, and Physiology
- Radiobiology and Genome Integrity
- 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
Overview
Medical Research Interests
DNA Replication; Genomic Instability
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Bleichert lab
Research at a Glance
Yale Co-Authors
Frequent collaborators of Franziska Bleichert's published research.
Publications Timeline
A big-picture view of Franziska Bleichert's research output by year.
Research Interests
Research topics Franziska Bleichert is interested in exploring.
Ashish Kumar, PhD
Adam Krysztofiak, PhD
Faye Rogers, PhD
Peter M. Glazer, MD, PhD
Yanfeng Liu
13Publications
705Citations
DNA Replication
Publications
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, 1-11. PMID: 39604729, DOI: 10.1038/s41586-024-08237-8.Peer-Reviewed Original ResearchAltmetricConceptsOrigin 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 advancesDuplicationMechanismOrigins of DNA replication
Ekundayo B, Bleichert F. Origins of DNA replication. PLOS Genetics 2019, 15: e1008320. PMID: 31513569, PMCID: PMC6742236, DOI: 10.1371/journal.pgen.1008320.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCitationsAltmetricMeSH Keywords and ConceptsConceptsKingdoms of lifeDomains of lifeDaughter cellsDNA replicationReplication originsCell divisionAccurate duplicationDaughter strandsGenomic DNAHereditary informationSemiconservative replicationGenetic materialFull complementDNA synthesisDiscrete sitesDNABidirectional mannerReplicationDivergent strategiesChromosomesOrganismsDuplicationOriginCellsStrands
2018
Conformational control and DNA-binding mechanism of the metazoan origin recognition complex
Bleichert F, Leitner A, Aebersold R, Botchan MR, Berger JM. Conformational control and DNA-binding mechanism of the metazoan origin recognition complex. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: e5906-e5915. PMID: 29899147, PMCID: PMC6042147, DOI: 10.1073/pnas.1806315115.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsOrigin recognition complexRecognition complexAutoinhibited stateHeterohexameric origin recognition complexMetazoan origin recognition complexHuman origin recognition complexUnstructured N-terminal regionORC-DNA interactionDNA-binding channelMcm2-7 loadingNucleotide-dependent associationCryo-EM analysisDNA-binding mechanismN-terminal regionMinichromosome maintenance 2Replicative helicaseATPase domainAutoinhibited configurationContact DNAHelix foldCellular activitiesMaintenance 2Biochemical assaysDNACdc6
2017
Mechanisms for initiating cellular DNA replication
Bleichert F, Botchan MR, Berger JM. Mechanisms for initiating cellular DNA replication. Science 2017, 355 PMID: 28209641, DOI: 10.1126/science.aah6317.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCitationsAltmetricMeSH Keywords and ConceptsConceptsReplicative helicasesDNA replicationRing-shaped hexameric helicasesDNA replication factoriesDNA replication initiationDomains of lifeCellular DNA replicationDNA helixReplisome assemblyReplication initiationMolecular choreographyHexameric helicasesReplication factoriesAccessory proteinsHelicasesDNA synthesisMultistep processDNAHelixReplicationProteinMechanismInitiationAssemblyLoaderInterdomain Communication of the Chd1 Chromatin Remodeler across the DNA Gyres of the Nucleosome
Nodelman IM, Bleichert F, Patel A, Ren R, Horvath KC, Berger JM, Bowman GD. Interdomain Communication of the Chd1 Chromatin Remodeler across the DNA Gyres of the Nucleosome. Molecular Cell 2017, 65: 447-459.e6. PMID: 28111016, PMCID: PMC5308885, DOI: 10.1016/j.molcel.2016.12.011.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsChromatin remodelersDNA gyresATPase motorChd1 chromatin remodelerDNA-binding domainDomain-domain communicationNucleosome assemblyNucleosome spacingNucleosomal DNAInterdomain communicationChd1 remodelerNucleosomesGenomic DNARemodelersDomain arrangementNucleosome coreDNAUnique organizationChromodomainDomain
Academic Achievements & Community Involvement
honor ERC Starting Grant
International AwardDetails10/01/2017Switzerlandhonor Miller Research Fellowship
Other AwardDetails07/01/2010United Stateshonor Stanford Biochemistry Founders’ Award for Doctoral Excellence
National AwardDetails05/01/2010United Stateshonor Boehringer Ingelheim Fonds PhD Fellowship
International AwardDetails01/01/2005Germany
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