Frank Uhlmann

Chromosome Segregation Laboratory

Aneuploidy, i.e. missing or supernumerary chromosomes, is a hallmark of malignant tumour progression. A large number of genes that orchestrate faithful chromosome segregation during mitotic cell divisions are tumour suppressors or turn into potent oncogenes if misregulated.

The aim of the Chromosome Segregation Laboratory is to investigate cellular mechanisms that safeguard accurate chromosome segregation. In particular, we are investigating the contribution of structural chromosomal proteins to sister chromatid cohesion and chromosome condensation, essential processes that ensure faithful segregation of the centimetre-long chromosomal DNA molecules within micrometre-sized cells.

A second topic of our research is the regulation of ordered mitotic progression by the cell division cycle machinery.

The budding yeast rDNA locus

The budding yeast rDNA locus, here visualized via a fluorescent rDNA binding protein, comprises ca. 500 μm of DNA. It is folded into a much more compact chromosome arm structure, to make chromosome segregation into daughter cells during cell division possible. Shown is how a regulator of the chromosomal cohesin complex, Wpl1, finetunes the chromosome condensation status. Scale bar, 5 μm.

Selected publications

Lopez-Serra L, Kelly G, Patel H, Stewart A, Uhlmann F. The Scc2-Scc4 complex acts in sister chromatid cohesion and transcriptional regulation by maintaining nucleosome-free regions. Nat Genet. 2014;46(10):1147-51

Murayama Y, Uhlmann F. Biochemical reconstitution of topological DNA binding by the cohesin ring. Nature. 2014;505(7483):367-71

Lopez-Serra L, Lengronne A, Borges V, Kelly G, Uhlmann F. Budding yeast wapl controls sister chromatid cohesion maintenance and chromosome condensation. Curr Biol. 2013; 7;23(1):64-9

Bouchoux C, Uhlmann F. A Quantitative Model for Ordered Cdk Substrate Dephosphorylation during Mitotic Exit. Cell. 2011 Nov 11;147(4):803-14.

Borges V, Lehane C, Lopez-Serra L, Flynn H, Skehel M, Rolef Ben-Shahar T, Uhlmann F. Hos1 deacetylates Smc3 to close the cohesin acetylation cycle. Mol. Cell. 2010;39:677-688

López-Avilés S, Kapuy O, Novák B, Uhlmann F. Irreversibility of mitotic exit is the consequence of systems level feedback. Nature. 2009;459:592-595

D'Ambrosio C, Schmidt CK, Katou Y, Kelly G, Itoh T, Shirahige K, Uhlmann F. Identification of cis-acting sites for condensin loading onto budding yeast chromosomes. Genes Dev. 2008;22:2215-2227

Rolef Ben-Shahar T, Heeger S, Lehane C, East P, Flynn H, Skehel M, Uhlmann F. Eco1-dependent cohesin acetylation during establishment of sister chromatid cohesion. Science. 2008;321,563-566

Frank Uhlmann

frank.uhlmann@crick.ac.uk
+44 (0)20 379 62059

  • Qualifications and history
  • 1997 PhD, University of Tübingen/ Memorial Sloan-Kettering Cancer Center, Germany/ USA
  • 1997 Postdoctoral Fellow, Research Institute of Molecular Pathology, Austria
  • 2000 Established lab at the Imperial Cancer Research Fund, UK (in 2002 the Imperial Cancer Research Fund became Cancer Research UK)
  • 2015 Group Leader, the Francis Crick Institute, London, UK