Chromosomal Fragile Sites and Extremely Large Genes – Oestergaard group

Common chromosomal fragile sites (CFSs) are regions of the genome that are highly unstable. CFSs host extremely large genes. We are trying to understand why extremely large genes cause genomic instability and how mutations arise at CFSs. Moreover, we aim to unravel the biological function of CFSs.

We use chicken and human cell lines as model systems. Our approach is mainly based on molecular genetics/CRISPR-Cas9, which we combine with a wide range of techniques such as fluorescence microscopy of living or immunostained cells, FISH, clonogenic survival, western blot, molecular cloning and qPCR.

Ambjorn, S.M., Duxin, J.P., Hertz, E.P.T., Nasa, I., Duro, J., Kruse, T., Lopez-Mendez, B., Rymarczyk, B., Cressey, L.E., van Overeem Hansen, T., et al. (2021). A complex of BRCA2 and PP2A-B56 is required for DNA repair by homologous recombination. Nat Commun 12, 5748. https://doi.org/10.1038/s41467-021-26079-0

Shao, X., Joergensen, A.M., Howlett, N.G., Lisby, M., and Oestergaard, V.H. (2020). A distinct role for recombination repair factors in an early cellular response to transcription-replication conflicts. Nucleic Acids Res 48, 5467-5484. 10.1093/nar/gkaa268. https://doi.org/10.1093/nar/gkaa268

Pentzold, C., S. A. Shah, N. R. Hansen, B. Le Tallec, A. Seguin-Orlando, M. Debatisse, M. Lisby, and V. H. Oestergaard. "Fancd2 Binding Identifies Conserved Fragile Sites at Large Transcribed Genes in Avian Cells." Nucleic Acids Res 46, no. 3 (2018): 1280-94. https://dx.doi.org/10.1093/nar/gkx1260.

Voutsinos, V., S. H. N. Munk, and V. H. Oestergaard. "Common Chromosomal Fragile Sites-Conserved Failure Stories." Genes (Basel) 9, no. 12 (2018). https://dx.doi.org/10.3390/genes9120580.

Oestergaard, Vibe H., and Michael Lisby. "Transcription-Replication Conflicts at Chromosomal Fragile Sites—Consequences in M Phase and Beyond." Chromosoma (2016). https://dx.doi.org/10.1007/s00412-016-0617-2.

I, Gallina, Christiansen SK, Pedersen RT, Lisby M, and Oestergaard VH. "Topbp1-Mediated DNA Processing During Mitosis." (2015). https://dx.doi.org/10.1080/15384101.2015.1128595.

Oestergaard, Vibe H., and Michael Lisby. "Topbp1 Makes the Final Call for Repair on the Verge of Cell Division." Molecular & Cellular Oncology (2015): 00--00. https://dx.doi.org/10.1080/23723556.2015.1093066.

RT, Pedersen, Kruse T, Nilsson J, Oestergaard VH, and Lisby M. "Topbp1 Is Required at Mitosis to Reduce Transmission of DNA Damage to G1 Daughter Cells." 2015). https://dx.doi.org/10.1083/jcb.201502107.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PhD student: Jiayi Li

Post doc: Henning Ummethum