DNA Metabolism and Cell Cycle Regulation
My research interests involve understanding how cells duplicate their genetic information with high fidelity and preserve the integrity of their genome. To do this, we are currently using two model systems. One involves a single-cell organism, the budding yeast Saccharomyces cerevisiae, and the other involves human cell culture. Both yeast and human cells perform many of the same processes, including DNA replication, repair, recombination, and cell cycle regulation. Mutations in genes involved in these processes can lead to human disease, and findings in yeast and human cells will aid in understanding the duplication and the maintenance of the human genome.
The focus of our research is on a factor, essential for all of the above processes, called Replication Protein A (RPA). RPA is a complex composed of three subunits called RPA1, RPA2, and RPA3. The major biochemical activity of RPA is single-strand DNA (ssDNA) binding, and it is often referred to as the eukaryotic single-strand binding (SSB) protein. Although ssDNA binding is its major function, it is becoming clear that RPA is also actively coordinating replication, recombination, repair, and regulation through its ability to act as a 'bridge' between ssDNA and the proteins necessary to act on the DNA. Our interest is in understanding the mechanism for coordination of these processes by RPA.
My research goals lie not only in understanding DNA metabolism, but also in creating an environment for students to gain wide range of experience in techniques, to foster collaboration, and to encourage and develop independent thinking. Students will be able to utilize these experiences to understand issues concerning science and human health, and they will develop tools and skills necessary to understand and address these issues in their professional careers.
Haring, S. J., Mason, A. D., Binz, S. K., and Wold, M. S. (2008) "Cellular functions of human RPA1: Multiple roles of domains in replication, repair, and checkpoints" J Biol Chem 283:19095-19111.
Grudic, A, Jul-Larsen, A., Haring, S. J., Wold, M. S., Lonning, P. E., Bjerkvig, R., and Boe, S. O. (2007) "Replication protein A prevents accumulation of single-stranded telomeric DNA in cells that use alternative lengthening of telomeres" Nucleic Acids Res 35:7267-7278.
Haring, S. J. and Wold, M. S. (2007) "A common means to an end" Nat Struct Mol Biol 14:176-177.
Binz, S. K., Dickson, A. M., Haring, S. J., and Wold, M. S. (2006) "Functional assays for replication protein A (RPA)" Methods Enzymol 409:11-38.
Malone, R. E., Haring, S. J., Pansegrau, M. L., Foreman, K. E., Smith, S. M., Carpp, L., Houdek, D. R., Shah, B., and Lee, K. E. (2004) "The signal from the initiation of meiotic recombination to the first division of meiosis" Eukaryot Cell 3:598-609.
Haring, S. J., Lautner, L. J., Comeron, J. M., and Malone R. E. (2004) "A test of the CoHR motif associated with meiotic double strand breaks in Saccharomyces cerevisiae" EMBO Rep 5:41-46.
Haring, S. J., Halley, G. R., Jones, A. J., and Malone, R. E. (2003) "Properties of natural double strand break sites at a recombination hotspot in Saccharomyces cerevisiae" Genetics 165:101-114.