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 not only in their professional careers, but also in their everyday lives.
Piya, G, Mueller, EN, Haas, HK, Ghospurkar, PL, Wilson, TM, Jensen, JL, Colbert, CL, and Haring, SJ (2015) "Characterization of the interaction between Rfa1 and Rad24 in Saccharomyces cerevisiae." PLoS One 10(2): e0116512 (Open Access). PMID: 25719602. DOI: 10.1371/journal.pone.0116512.
Ghospurkar, PL, Wilson, TM, Severson, AL, Klein, SJ, Khaku, SK, Walther, AP, and Haring, SJ (2015) "Distinct roles for the Rfa2 N-terminus in the DNA damage response and adaptation in Saccharomyces cerevisiae." Genetics 199(3): 711-727 (Open Access). PMID: 25595672. DOI: 10.1534/genetics.114.173211.
Ghospurkar, PL, Wilson, TM, Liu, S, Oakley, GG, Herauf, A, Steffes, J, Mueller, EN, and Haring, SJ (2015) "Phosphorylation and cellular function of the human Rpa2 N-terminus in the yeast Saccharomyces cerevisiae." Exp Cell Res 331(1): 183-199 (Open Access). PMID: 25499885. DOI: 10.1016/j.yexcr.2014.12.002.
Kemp, MG, Mason, AC, Carreira, A, Reardon, JT, Haring, SJ, Borgstahl, GE, Kowalcyzkowski, SC, Sancar, A, and Wold, MS (2010) "An alternative form of Replication Protein A expressed in normal human tissues supports DNA repair." J Biol Chem 285(7): 4788-4797. PMID: 19996105. DOI: 10.1074/jbc.M109.079418.
Haring, SJ, Humphreys, TD, and Wold, MS (2010) "A naturally-occurring human RPA subunit homolog does not support DNA replication or cell cycle progression." Nucleic Acids Res 846-858. PMID: 19942684. DOI: 10.1093/nar/gkp1062.
Koehn, DR, Haring, SJ, Williams, JM, and Malone, RE (2009) "Targeting components of a recombination initiation complex to unnatural sites for recombination." Genetics 182(2): 447-458. PMID: 19332879. DOI: 10.1534/genetics.109.102640.
Mason, AC, Haring, SJ, Pryor, JM, Staloch, CA, Gan, TF, and Wold, MS (2009) "An alternative form of RPA prevents viral replication in vitro." J Biol Chem 284(8): 5324-5331. PMID: 19116208. DOI: 10.1074/jbc.M808963200.