David S. Pederson

Office 802-656-8586
    Lab 802-656-8587
302 Stafford
Regulation of Transcription and Replication

Dr. Pederson’s research career began with a study of wild horses while working as a cowboy in California. He went on to study cell migration in developing embryos at the University of Chicago, and received his Ph.D. from the University of Rochester.

Research Interests

Cancer Biology
Structural Biology & Protein Function
DNA Replication & Repair

Current research in the Pederson lab focuses on two areas, Control of DNA Replication and Base Excision Repair of Damaged DNA in Chromatin. Cells possess regulatory networks which ensure that mitosis does not occur until DNA replication is complete; other regulatory networks suppress transcription during mitosis. We are studying a protein, known as Clf1p, that conceivably helps coordinate DNA replication and transcription during the cell cycle. Clf1p associates with replication origins in DNA, and with factors that trigger the onset of replication during S phase of the cell cycle. Clf1p also plays an essential role in pre-mRNA splicing. Our working hypothesis is that Clf1p acts as a scaffold that helps recruit and properly orient other proteins that act in one or the other of these two processes. We are using molecular genetic techniques to test this hypothesis. Hydroxyl radical-mediated damage to DNA can lead to elevated cell lethality and mutations that predispose cells to form cancers. The base excision-mediated repair of such damages in naked DNA is quite well understood but very little is known about how these same enzymes act on damaged DNA in chromatin. We are studying this process in collaboration with the Wallace laboratory, by assembling nucleosomes that contain selected lesions, located at selected sites in the nucleosome. We then incubate these model nucleosomes with highly purified human DNA repair enzymes to identify rate-limiting steps in the repair of such lesions. Our long-term goal is to identify factors that overcome these rate-limiting steps in eukaryotic cells.

Selected Publications

Rice, T. S., Ding, M., Pederson, D. S. and Heintz, N. H. The highly conserved tRNAHis guanylyltransferase Thg1p interacts with the origin recognition complex and is required for the G2/M phase transition in the yeast Saccharomyces cerevisiae. Eukaryotic Cell 2005 Apr;4(4):832-5.

Zhu, W., Rainville, I. R., Ding, M., Bolus, M., Heintz, N. H. and Pederson D. S. Evidence that the pre-mRNA splicing factor Clf1p plays a role in DNA replication in Saccharomyces cerevisiae. Genetics 2002 Apr;160(4):1319-33.

Geraghty, D. S., Ding, M., Heintz, N. H. and Pederson, D. S. Premature structural changes at replication origins in a yeast minichromosome maintenance (MCM) mutant. J. Biol. Chem. 2000. Jun 16;275(24):18011-21.

Geraghty, D.S., Sucic, H., Chen, J., and Pederson, D.S. Evidence that partial unwrapping of DNA from nucleosomes facilitates the binding of heat shock factor following DNA replication in yeast. J. Biol. Chem., 1998, Aug 7;273(32):20463-20472.

Chen, J., Ding, M., and Pederson, D.S. Binding of TFIID to the CYC1 TATA boxes in yeast occurs independently of upstream activating sequences. Proc. Natl. Acad. Sci. USA, 1994, Dec. 6;91(25):11909-119013.

Pederson, D.S., and Fidrych, T. Heat shock factor can activate transcription while bound to nucleosomal DNA in Saccharomyces cerevisiae. Mol. Cell. Biol. 1994, Jan;14(1):189-99

All Pederson publications