| Citation | Dr Frank Uhlmann, Group Leader, The Francis Crick Institute
Frank Uhlmann elegantly combines genetics with genomics, cell biology and biochemistry to study the mechanisms and regulation of mitosis. His discovery of 'separase', the protease that cleaves the cohesive links between sister chromatids to trigger anaphase, as a postdoc with Kim Nasmyth, is a key contribution to our understanding of the cell cycle. Independently, Uhlmann has made major contributions to our understanding of the mechanisms of sister chromatid cohesion, and their relationship to cell cycle regulation. He generated the first chromosome-wide high resolution maps of proteins involved in chromosome packaging and segregation. He showed that yeast cohesins accumulate at sites of converging transcription distinct from the sites where their loading factors bind, apparently reflecting interaction with the transcription apparatus; and that cohesin loading factors are recruited to specific chromosomal sites through interaction with the nucleosome remodelling complex Rsc. In exciting recent work, Uhlmann has established an in vitro system for cohesin loading using purified components, opening the way to a full molecular understanding of this fascinating complex. Uhlmann has identified genes required for cohesion establishment, and shown that one of these, EcoI, acetylates cohesin during DNA replication, thereby locking it onto DNA. Uhlmann's studies of the link between cohesion regulation and the cell cycle have shown that as well as cleaving cohesin, separase promotes mitotic exit by activating the Cdc14 phosphatase in a protease-independent manner. He has characterised the role of Cdc14 in mitotic exit, and demonstrated its role in resolution of cohesin-independent rDNA linkages. Uhlmann's laboratory has also provided novel insights into the ordering of events during mitosis. These include the demonstration that irreversibility of mitotic exit results from systems level feedback downregulation of Cdk activity, rather than proteolysis of cyclin per se, and the development of a model for the sequential dephosphorylation of Cdc14 substrates during mitotic exit.
|