Catherine A. Fox
Credentials: Conservation and diversity in mechanisms that control the inheritance and expression of eukaryotic chromosomes
Position title: Professor
Phone: (608) 262-9370
5204C Biochemical Sciences Building
440 Henry Mall, Madison, WI 53706
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
Our lab wants to understand how different types of chromatin structures have an impact on genome duplication and stability in eukaryotic cells. We use budding yeast (Saccharomyces cerevisiae) as our model organism for many reasons. First, many biochemical and genetic experiments that have defined the mechanisms of genome duplication have been performed in this model organism, providing us with a wealth of knowledge and tools to perform hypothesis-driven experiments in a cellular context. Second, budding yeast are an exceptionally tractable model organism where biochemical, molecular, genetic, microbiological and genomic approaches can be combined to test sophisticated models. Third, because the basic processes we study are well conserved, what we learn in yeast guides the experiments and interpretations from research in more complex eukaryotic organisms. This last point is important because genome duplication and stability are critical for normal cell proliferation and differentiation in multicellular organisms, including humans. Alterations in genome duplication programs, as well as the associated defects in genome stability, are hallmarks of both normal aging and cancerous cells.
DNA replication origins (origins) are a major interest. Origins are the positions on chromosomes where the chromosomal DNA is unwound to allow for new DNA synthesis. Origin winding is the first step of genome duplication and is therefore highly regulated. In eukaryotic cells, this step is tightly coupled to the cell cycle. In G1-phase, multiple proteins and protein complexes, including the Origin Recognition Complex (ORC), work together to load the replicative helicase complex, called the MCM complex. The MCM complex is loaded as an inert double-hexamer containing two hexameric helicases. Only in S-phase is the MCM complex activated and converted into the two active MCM helicases. This activation triggers origin unwinding and the two active helicase holoenzymes, now each encircling single-stranded DNA, will continue to unwind the parental DNA helix for new DNA synthesis. While these basic biochemical steps are now fairly well understood, the field has a comparatively poor understanding of how these steps contend with or are regulated by the complex chromatin structures that that exist in cells. This issue is important because in eukaryotic cells, each chromosome relies on many individual origins physically distributed across its length for its efficient and accurate duplication. Because chromatin structures vary considerably across a chromosome’s length, this fact means that the basic origin machinery must contend with a variety of different chromatin structures. How the core protein-protein and protein-DNA interactions involving the core replication machinery adapt to work in different chromatin environments is unknown.
We are using genetic, genomic and biochemical approaches to define the different chromatin structures that affect the steps required for origin function. We have defined chromatin features that promote the binding of the Origin Recognition Complex (ORC) to DNA, as well as the subsequent loading of the MCM complex in G1. We have also defined chromatin features that can inhibit these steps. We are trying to understand how the various modes of chromatin regulation work with the basic core replication machinery to insure that chromosomes are efficiently and accurately duplicated during cell division.
Perform a customized PubMed literature search for Catherine A. Fox
- Fox, C.A., K. Lethcoe, and R.O. Ryan. (2021). Calcium-induced release of cytochrome c from cardiolipin nanodisks: Implications for apoptosis. Biochimica et biophysica acta. Biomembranes, 1863: 183722.
- Fox, C.A., A. Moschetti, and R.O. Ryan. (2021). Reconstituted HDL as a therapeutic delivery device. Biochimica et biophysica acta. Molecular and cell biology of lipids, 1866: 159025.
- Hoggard, T., A.J. Hollatz, R.E. Cherney, M.R. Seman, and C.A. Fox. (2021). The Fkh1 Forkhead associated domain promotes ORC binding to a subset of DNA replication origins in budding yeast. Nucleic acids research, 49: 10207-10220.
- Kose, K., C.A. Fox, A. Rossi, M. Jain, M. Cordova, S.W. Dusza, M. Ragazzi, S. Gardini, E. Moscarella, A. Diaz, R. Pigem, S. Gonzalez, A. Bennassar, C. Carrera, C. Longo, M. Rajadhyaksha, and K.S. Nehal. (2021). An international 3-center training and reading study to assess basal cell carcinoma surgical margins with ex vivo fluorescence confocal microscopy. Journal of cutaneous pathology, 48: 1010-1019.
- Fox, C.A., and D.M. McLoughlin. (2021). Speed of electroconvulsive therapy for depression: Effects of electrode placement. Acta psychiatrica Scandinavica, 143: 444-452.
- Roberts, L.C., L.S. van Helden, C.A. Fox, F. Fiff, and D.J. Visser. (2020). Provincial Veterinary Services respond to drought in South Africa. Revue scientifique et technique (International Office of Epizootics), 39: 407-415.
- Hoggard, T., C.A. Müller, C.A. Nieduszynski, M. Weinreich, and C.A. Fox. (2020). Sir2 mitigates an intrinsic imbalance in origin licensing efficiency between early- and late-replicating euchromatin. Proceedings of the National Academy of Sciences of the United States of America, 117: 14314-14321.
- Fox, C.A., and R.O. Ryan. (2020). Dye binding assay reveals doxorubicin preference for DNA versus cardiolipin. Analytical biochemistry, 594: 113617.
- McDaniel, S.L., A.J. Hollatz, A.M. Branstad, M.M. Gaskill, C.A. Fox, and M.M. Harrison. (2020). Tissue-Specific DNA Replication Defects in Drosophila melanogaster Caused by a Meier-Gorlin Syndrome Mutation in Orc4. Genetics, 214: 355-367.
- Gill, M., J.M. Grant-Kels, and C.A. Fox. (2019). Absence of lesional features on reflectance confocal microscopy: Quality control steps to avoid false-negative results. Journal of the American Academy of Dermatology, 81: e71-e73.