DNA provides a critical template within each individual cell, encoding information that allows vital functions, both basic and specialized, to be carried out. Many steps are involved in ensuring that DNA is maintained, used accurately, and then passed on as a precise copy when a cell divides. The processes underlying each of these steps are diverse, however they all involve sets of proteins that act on nucleic acid in a highly regulated manner. The labs grouped within the sub-specialty of Nucleic Acid Biology are equally diverse, but are unified by an interest in the mechanisms responsible for fundamental cellular functions that involve nucleic acid. Research in this area is focused on such topics as DNA replication, DNA recombination, RNA editing, and RNA transport. Since the regulation of nucleic acids ultimately determines a cell's phenotype, there is a direct link between Nucleic Acid Biology and cancer. For instance, any time a DNA sequence error goes unchecked, a mutation is introduced that could potentially lead to cellular transformation. The impact of Nucleic Acid Biology is also illustrated by the observation that certain viral infections are associated with the development of cancer. In many of these cases, evasion of normal regulation during the process of RNA biogenesis is key to the viral life cycle.

Several laboratories within Huntsman Cancer Institute focus on varied aspects of Nucleic Acid Biology. The diverse range of experimental approaches and systems among these laboratories provides depth to the program and exciting opportunities for discussion and collaboration. Students have access to many courses that draw on the expertise of the faculty involved in Nucleic Acid Biology research. Formal classwork is complemented by journal clubs as well as special interest group meetings such as "RNA Round-up". Researchers in this, as well as other areas, benefit from access to strong core facility support. These include facilities for DNA and peptide sequencing and synthesis, NMR, and mass spectrometry.

Participating Faculty

Brenda Bass - The Bass laboratory studies a group of RNA editing enzymes called adenosine deaminases that act on RNA (ADARs). ADARs catalyze the conversion of adenosines to inosines within cellular and viral mRNAs so that multiple protein isoforms can be expressed from a single encoded sequence. The laboratory uses C. elegans as a biological system with which to test hypotheses made during in vitro biochemical studies.

Cynthia J. Burrows - The Burrows lab studies DNA damage resulting from exposure to oxidizing and alkylating agents. Unrepaired DNA damage is linked to carcinogenesis because of misincorporations opposite damaged bases, particularly 8-oxoguanine and its further oxidation products. We investigate the chemistry of 8-oxoguanine and related lesions including sequence and structural effects on in vitro reactivity, misincorporation of bases by DNA polymerases, and formation of DNA-protein cross-links.

Brad Cairns - We are interested in the biology of ATP-dependent chromatin remodeling complexes; including their composition, activities, regulation and targeting. Many genes that play key roles in cell proliferation and differentiation are repressed by chromatin, and are derepressed at the proper time by the action of chromatin remodeling complexes. We combine genetics, biochemistry, molecular biology, and DNA microarray analysis to discover and characterize their functions.

Dana Carroll - My lab is currently working on a method to improve the frequency of gene targeting through homologous recombination. Our approach is based on an understanding of the principal molecular mechanism by which recombination proceeds in higher eukaryotic cells. We are using chimeric nucleases to direct recombinagenic double-strand breaks to specific sites in DNA, and we are testing the feasibility of this approach using injection of substrates and enzymes into Xenopus oocyte nuclei, where recombination can be very efficient, but depends on DNA ends.

Sheila S. David - Mechanisms of Recognition and Repair of DNA damage by DNA repair enzymes. Dysfunctional DNA repair has been implicated in cancer, and in addition inhibition of DNA repair is a new strategy for increasing the efficacy of cancer therapeutics. Thus, a fundamental understanding the molecular details involved in the recognition of DNA damage by DNA repair enzymes, and the chemistry involved in the repair process is needed. This will aid in the development of new therapeutic approaches targeted at DNA and DNA repair enzymes. Biochemical approaches, enzymology, oligonucleotide chemistry, site-directed mutagenesis, kinetics.

Tim Formosa - Our lab studies the composition and architecture of DNA replication complexes in eukaryotes. Errors in DNA replication lead to genomic instability, so understanding how replication complexes are formed and regulated is a crucial aspect of understanding how genomes are maintained and accurately segregated to progeny. We use a combination of genetics and biochemistry in yeast cells to study interactions among replication components.

Janet E. Lindsley - My lab is interested in the mechanism of enzymes that manipulate DNA structure, and how those enzymes are involved in genome instability. One of these enzymes, DNA topoisomerase II, is the target of numerous anticancer drugs and has been implicated in causing chromosomal translocations. We use a combination of biochemistry, molecular biology and genetics to study the mechanisms of both the isolated enzymes and the chromosome translocations.

Katharine Ullman - We are interested in how the process of transport through the nuclear pore takes place. Regulated, bidirectional traffic through this gateway is critical to normal cell function and is a key step in the biogenesis of RNA. To study the nuclear pore, we take advantage of the large oocytes and eggs of the frog, Xenopus laevis, and use a combination of approaches, from in vitro biochemical analysis to in vivo transport studies. Ullman Lab.