University of Dundee

Professor Mike Stark

Regulation of Yeast Cell Growth and Division
Position: 
Emeritus Professor of Yeast Molecular Biology
Address: 
School of Life Sciences, University of Dundee, Dundee
Full Telephone: 
+44 (0) 1382 384250, int ext 84250
Email: 

Research

The availability of powerful classical and molecular genetic methodologies, a well annotated genome and the ability to carry out sophisticated biochemistry and cell biology make the yeast Saccharomyces cerevisiae a valuable model organism in which to study conserved regulatory mechanisms. A surprisingly large number of fundamental cellular processes are conserved between yeast and higher eukaryotes and I am interested in studying those molecular mechanisms that regulate growth and division using Saccharomyces cerevisiae as a model system.

My recent research has focused on Elongator, a conserved, six-subunit protein complex. Although Saccharomyces cerevisiae Elongator is non-essential for growth in the laboratory, it is essential for mammalian development and mutations in its Elp1 subunit are associated with Familial Dysautonomia, a neurodevelopmental disease. Over the past decade a variety of roles have been proposed for Elongator, but the principal and possibly only role of Elongator is to promote two related chemical modifications to the uridine residue that is present at the anticodon ‘wobble’ position (U34) in a subset of tRNAs. These U34 modifications (termed mcm5U and ncm5U) are required for wobble uridine-containing tRNAs to function efficiently in protein synthesis, and Elongator’s role in wobble uridine modification is conserved in plants, worms (C. elegans) and mammals.

Yeast Elp1 shows Hrr25-dependent phosphorylation and we have shown recently that this is required for Elongator functionality. Hrr25, a yeast casein kinase I orthologue, directly phosphorylates Elp1 and Elongator-dependent tRNA wobble uridine modification depends on phosphorylation of the Hrr25 sites along with other, adjacent phosphorylation sites that are not directly phosphorylated by Hrr25. The phosphorylated region is adjacent to a domain in Elp1 that we have shown to bind tRNA and we would like to understand, in molecular terms, how these phosphoregulatory and tRNA binding domains in Elp1 cooperate to promote wobble uridine modification, which is likely to be catalyzed by Elongator’s Elp3 subunit.

Publications

Abdel-Fattah, W. R., Jablonowski, D., Di Santo, R. T. A., Thüring, K. L., Scheidt, V., ten Have, S. M., Helm, M., Schaffrath, R. and Stark, M. J. R. (2015).
Phosphorylation of Elp1 by Hrr25 is required for Elongator-dependent tRNA modification in yeast.
PLoS Genetics e1004931. View Paper

Di Santo, R., Bandau, S. and Stark, M. J. R. (2014).
A conserved and essential basic region mediates tRNA binding to the Elp1 subunit of the Saccharomyces cerevisiae Elongator complex.  
Mol Microbiol. 92, 1227–1242.  View Paper

Makrantoni, V., Corbishley, S. J., Rachidi, N., Morrice, N. A., Robinson, D. A. and Stark, M. J. R. (2014).
Phosphorylation of Sli15 by Ipl1 is important for proper CPC localization and chromosome stability in Saccharomyces cerevisiae.
PLoS ONE 9, e89399. doi:10.1371/journal.pone.0089399  View Paper

Uthman, S., Bär, C., Scheidt, V., Liu, S., ten Have, S., Giorgini, F., Stark, M. J. R. and Raffael Schaffrath, R. (2013).
The amidation step of diphthamide biosynthesis in yeast requires DPH6, a gene identified through mining the DPH1-DPH5 interaction network.
PLoS Genet 9, e1003334.  View Paper

Keating, P., Rachidi, N., Tanaka, T. U. and Stark, M. J. R.  (2009).
Ipl1-dependent phosphorylation of Dam1 is reduced by tension applied on kinetochores.
J. Cell Sci. 122, 4375-4382.  View Paper

Makrantoni, V. and Stark, M. J. R. (2009).
Efficient chromosome bi-orientation and the tension checkpoint in Saccharomyces cerevisiae both require Bir1.
Mol. Cell. Biol. 29, 4552-4562.  View Paper

Lain, S., Hollick, J. J., Campbell, J., Staples, O., Higgins, M., Aoubala, M., McCarthy, A., Appleyard, V., Murray, K. E., Baker, L., Thompson, A., Mathers, J., Holland, S. J., Stark, M. J. R., Pass, G., Woods, J., Lane, D. P. and Westwood, N. J. (2008).
Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell 13, 454-463.  View Paper

King, E. M. J., Rachidi, N., Morrice, N., Hardwick, K. G. and Stark, M. J. R. (2007).
Ipl1p-dependent phosphorylation of Mad3p is required for the spindle checkpoint response to lack of tension at kinetochores.
Genes Devel. 21, 1163-1168.  View Paper

Fox, G.  C., Shafiq, M., Briggs, D. C., Knowles, P.P., Collister, M., Didmon, M., Makrantoni, V., Dickinson, R., Hanrahan, S., Totty, N., Stark, M. J. R., Keyse, S. M. and McDonald, N. Q. (2007).
Redox-mediated substrate recognition by Sdp1 defines a new group of tyrosine phosphatases. Nature 447, 487-492. (doi:10.1038/nature05804).  View Paper

Tanaka, T., Rachidi, N., Janke, C., Pereira, G., Galova, M., Schiebel, E., Stark, M. J. R. and Nasmyth, K. (2002).
Evidence that the Ipl1/Sli15 (Aurora kinase/INCENP) complex promotes chromosome bi-orientation by altering kinetochore-spindle pole connections.
Cell 108, 317-329.  View Paper