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Catherine Fox

Associate Professor of Biomolecular Chemistry

Address:

687 Medical Sciences

Telephone:

262-9370

Email:

cfox@wisc.edu

Research Fields:

Gene Expression

Cancer Genetics

Yeast and Fungi

Research Interests

DNA replication, gene expression and cell cycle. Chromosome structure and function.

Research Description

We are interested in mechanisms underlying the relationships between the cell cycle, chromatin structure and gene expression in eukaryotic cells. We combine genetic, molecular and biochemical approaches using yeast as our model organism. In one project we examine the role of the Origin Recognition Complex (ORC). ORC controls both chromosome replication and chromatin-mediated chromosome functions (transcription, segregations) in all eukaryotic organisms, but its mechanism is experimentally addressable in yeast. We want to understand how the different roles of ORC are regulated and related. In a second project, we are studying protein-protein interactions between ORC and the Sir1 protein. The Sir1 protein nucleates the assembly of specialized chromatin that represses transcription at only a few chromosomal positions. Interactions between ORC and Sir1 protein are confined to these positions even though ORC can bind at many positions in the genome. We want to understand what controls the high specificity of the Sir1p/ORC interaction in the genome, how this interaction is affected by the cell cycle and how it has evolved. A third project is open to study the composition of yeast heterochromatin and the dynamics of protein-protein interactions required for its assembly and stability during the cell cycle. In a fourth project, we are studying how two evolutionarily conserved DNA binding proteins, Fkh1 and Fkh2, regulate the cell cycle and chromatin structure.

Representative Publications

• McConnell, K.H. and C.A. Fox. 2006. Tolerance of Sir1p/Origin Recognition-Complex-dependent silencing for enhanced origin firing at HMRa. Mol. Cell. Biol. 26:1955-1966.
• Hou, Z., Bernstein, D.A., Fox, C.A* and J.L. Keck* (*co-senior authors). 2005. Structural basis of the Sir1-ORC interaction in transcriptional silencing. Proc. Natl. Acad. Sci. 102:8489-8494.
• Fox, C.A and K.H. McConnell. 2005. Toward a biochemical description of a transcriptionally silenced domain in Saccharomyces cerevisiae. J. Biol. Chem. 280:8629-8632.
• Bose, M.E., McConnell, K.H., Gardner K.A., Weinreich, M., Keck J.L., Muller U. and C.A. Fox. 2004. The origin recognition complex and Sir4 protein recruit Sir1p to yeast silent chromatin through independent interactions requiring a common Sir1p domain. Mol. Cell. Biol. 24:774-786.
• Palacios DeBeer, M.A., Muller U. and C.A. Fox. 2003. Differential DNA affinity specifies the activity of the origin recognition complex in budding yeast heterochromatin. Genes & Dev. 17:1817-1822.