Catherine A. Fox
 |
Associate Professor
Office: (608) 262-9370 |
Education
- B.S. 1986, University of California-Riverside;
- Ph.D. 1992, University of Wisconsin-Madison (M. Wickens);
- Postdoctoral 1992-96, University of California-Berkeley (J. Rine).
Honors & Awards
- Burroughs Wellcome Career Award in Biomedical Sciences, 1996;
- Shaw Scientist Award, 1998;
- American Cancer Society Research Scholar, 2002.
- Vilas Associate Award from the Graduate School, UW-Madison 2005-2007;
Research Interests
We are interested in the structure and function of eukaryotic chromosomes and focus primarily on understanding how chromosome structure, at the levels chromatin and nuclear architecture, regulate DNA replication and gene expression. We combine classical and reverse genetics, molecular and structural biology, biochemistry and whole genome methods in the budding yeast Saccharomyces cerevisiae. Projects Include:
1. Mechanisms that regulate target-site selection and function of the Origin Recognition Complex (ORC): ORC is a complex of 6 different proteins conserved from yeast to humans. Its main job is to function in DNA replication at sites called origins, the positions where DNA replication initiates. Eukaryotic chromosomes have an excess of replication origins, and at some origins ORC has additional functions in chromatin structure. These two different roles of ORC may be regulated by how ORC binds to DNA and chromatin. ORC-chromatin interactions play a larger role than ORC-DNA interactions in ORC binding in human compared to yeast cells. But we have discovered a subset of poorly studied yeast origins that also rely heavily on ORC-chromatin interactions. Biochemical, whole-genome, and classic genetics are being used to study these novel origins.
2. Structure-function studies of protein-protein interactions involving ORC: ORC interacts with many different proteins that regulate its function. We study ORC’s interaction with protein-partners that endow it with unique functions in chromatin structure. We have used structural biology, in collaboration with our colleague Dr. Jim Keck, to study protein-protein interactions involving ORC. We are also studying domains in ORC that control ORC-chromatin interactions in collaboration with our colleague Dr. John Denu using both molecular and chemical biology approaches.
3. Cell-cycle regulation of chromosome structure and chromosome-associated proteins: Chromosome structure is dynamic during every cell cycle. Proteins that regulate the association of chromosomes with the nuclear membrane help control cell cycle regulated changes in chromatin structure. We are using unbiased forward genetic screens to reveal novel genes that modulate chromosomal architecture within the nucleus and in response to cell cycle changes. A variety of approaches are being used to study these genes and their encoded proteins.
Publications of Note
Bose, ME, McConnell, KH, Gardner KA, Weinreich, M, Keck JL, Müller U and CA Fox. 2004. The Origin Recognition Complex and Sir4 protein recruit Sir1 to yeast silent chromatin through independent interactions requiring a common Sir1 domain. Mol. Cell. Biol. 24: 774-786.
Weinreich, M, DeBeer, MA and CA Fox. 2004. The activities of eukaryotic replication origins in chromatin. Biochemica et Biophysica Acta 1677: 142-157.
Fox, CA and KH McConnell. 2005. Toward a biochemical description of a transcriptionally silenced chromosomal domain in Saccharomyces cerevisiae. J. Biol. Chem. 280: 8629-8632.
Hou, Z, Bernstein DA, CA Fox and JL Keck. 2005. Structural basis of the Sir1-ORC interaction in transcriptional silencing. Proc. Natl Acad Sci. 102: 8489-8494
McConnell, KH, Müller P and CA Fox. 2006. Tolerance of Sir1/Origin Recognition Complex-dependent silencing for enhanced origin firing at HMRa. Mol. Cell. Biol. 26:1955-1966.
Hou Z, Danzer JR, CA Fox and JL Keck. 2006. Structure of the Sir3 protein Bromo Adjacent Homology (BAH) domain from S. cerevisiae at 1.95Å resolution. Protein Science. 15:1182-1186.
Gabrielse, C, Miller, CT, DeWard, A, KH McConnell, CA Fox and M Weinreich. 2006. A Dbf4p BRCT-like domain required for the response to replication-fork arrest in budding yeast. Genetics 173: 541-555.
Casey, L, Patterson, E, Müller, U and CA Fox. 2008. Conversion of a replication origin to a silencer by a pathway shared by FKH1 and CLB5 Mol. Biol. Cell. 19: 608-622. (Epub, Nov. 2007. Print edition Feb. 2008)
Patterson, E.E. and C.A. Fox. 2008. The Ku complex in silencing the cryptic mating-type loci of Saccharomyces cerevisiae. Genetics 180: 771-783.
Fox CA, M Weinreich 2008. Beyond heterochromatin: SIR2 inhibits the initiation of DNA replication. Cell Cycle 7: 3330-3334.
Hou Z, Danzer JR, Mendoza L, Bose ME, Müller U, Williams B, Fox CA. 2008.
Phylogenetic conservation and homology modeling help reveal a novel domain within the budding yeast heterochromatin protein Sir1. Mol Cell Biol. 2008 Nov 24. [Epub ahead of print]
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University
of Wisconsin - Department
of Biomolecular Chemistry
First published: 01/01/05 Last updated:19 March 2009 Email Biomolecular Chemistry
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