• campus:  a to z index
• map
• directory
• calendar

Search:

Tim Formosa

Associate Professor of Biochemistry

B.S. University of California, Davis

Ph.D. University of California, San Francisco

Research

References

tim@biochem.utah.edu

 

Research

We use yeast to study a highly conserved complex called yFACT. yFACT binds to nucleosomes and reorganizes them into an alternative structure whose nature remains poorly understood. This reorganization of the basic subunits of chromatin changes the properties of chromatin, and the ability to make this change in the structure of nucleosomes is essential for the viability of eukaryotic cells. When yFACT subunits are mutated in yeast, both RNA transcription and DNA replication are affected, so yFACT is both an important transcription factor and an important DNA replication factor. We use purified proteins to examine the activity of yFACT in vitro, and we use mutations in yFACT subunits to study the function of yFACT in vivo. This combination of genetics and biochemistry allows us to study the important features of yFACT more rapidly and more fully than would be possible using either approach alone. In collaboration with Chris Hill's lab, we have also begun to study the 3-dimensional structure of yFACT using X-ray crystallography.

Chromatin proteins such as histones and other DNA binding factors typically limit the accessibility of DNA in eukaryotic cells. Remodeling factors solve this problem by using ATP hydrolysis to move nucleosomes along the DNA, making different sequences accessible in the linkers between nucleosomes. yFACT makes nucleosomal DNA accessible, but it does not use ATP hydrolysis and it does not move the nucleosomes. We are interested in determining how yFACT accomplishes this.

One set of approaches we use involves studying how purified components behave in vitro. This biochemistry allows us to ask defined mechanistic questions about the activity of yFACT. Another set of approaches involves asking questions about what yFACT does in living cells. This genetic analysis allows us to ask which processes actually use yFACT and how its activities in the purified systems relate to its functions in vivo. We have also collaborated with David Stillman's lab to study the role of yFACT in promoting the formation of transcription intermediates in whole cells. Biochemistry tells us how proteins and DNA behave in isolation, but it cannot tell us what is important about their functions in cells.  Genetics tells us what is important about cellular processes, but provides little specific information about mechanisms.  Using biochemistry and genetics together is therefore synergistic and allows insights to be gained into the fundamental workings of cells. We are using this balanced approach to explore the function of yFACT in mediating transcription and replication.

References