Franziska Bleichert, PhD
Research & Publications
Accurate and timely replication of chromosomal DNA is essential to sustain genome integrity and requires highly efficient replication machineries that will synthesize approximately 2 light years of DNA during a human’s life time. In the Bleichert lab, we are interested in understanding how replication machineries are assembled on the chromatin template during replication initiation, how DNA and chromatin is subsequently replicated, and how the chromatin architecture in turn helps regulate key replication events. To this end, we use an integrated mix of biochemical, biophysical, structural (single-particle cryo-electron microscopy and X-ray crystallography), and in vivo genetic approaches. Our goal is to establish molecular models for how the complex interplay between chromatin structure and DNA replication contributes to maintaining chromosome copy number and genome stability, and for how deregulation of these events contributes to human disease.
DNA Replication; Genomic Instability
- A mechanism of origin licensing control through autoinhibition of S. cerevisiae ORC·DNA·Cdc6Schmidt 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.
- Structural mechanism for replication origin binding and remodeling by a metazoan origin recognition complex and its co-loader Cdc6Schmidt 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.
- Mechanisms of replication origin licensing: a structural perspectiveBleichert 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.
- Origins of DNA replicationEkundayo B, Bleichert F. Origins of DNA replication PLOS Genetics 2019, 15: e1008320. PMID: 31513569, PMCID: PMC6742236, DOI: 10.1371/journal.pgen.1008320.
- Conformational control and DNA-binding mechanism of the metazoan origin recognition complexBleichert 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.
- Mechanisms for initiating cellular DNA replicationBleichert F, Botchan MR, Berger JM. Mechanisms for initiating cellular DNA replication Science 2017, 355 PMID: 28209641, DOI: 10.1126/science.aah6317.
- Interdomain Communication of the Chd1 Chromatin Remodeler across the DNA Gyres of the NucleosomeNodelman 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.
- Crystal structure of the eukaryotic origin recognition complexBleichert F, Botchan MR, Berger JM. Crystal structure of the eukaryotic origin recognition complex Nature 2015, 519: 321-326. PMID: 25762138, PMCID: PMC4368505, DOI: 10.1038/nature14239.
- A Meier-Gorlin syndrome mutation in a conserved C-terminal helix of Orc6 impedes origin recognition complex formationBleichert F, Balasov M, Chesnokov I, Nogales E, Botchan MR, Berger JM. A Meier-Gorlin syndrome mutation in a conserved C-terminal helix of Orc6 impedes origin recognition complex formation ELife 2013, 2: e00882. PMID: 24137536, PMCID: PMC3791464, DOI: 10.7554/elife.00882.
- A Dimeric Structure for Archaeal Box C/D Small RibonucleoproteinsBleichert F, Gagnon KT, Brown BA, Maxwell ES, Leschziner AE, Unger VM, Baserga SJ. A Dimeric Structure for Archaeal Box C/D Small Ribonucleoproteins Science 2009, 325: 1384-1387. PMID: 19745151, PMCID: PMC2975540, DOI: 10.1126/science.1176099.