2000 Ph.D. University of Minnesota
1994 B.A. Macalester College, St. Paul, Minnesota
Area(s) of Expertise
Chemical Biology and Biotechnology
The interests of Prof. Beuning’s lab are to understand cellular responses to DNA damage. All organisms experience damage to their genetic material from environmental and endogenous sources. Multiple systems exist to identify and remove damaged bases from DNA in organisms from bacteria to humans. For example, the bacterial SOS response, involving the upregulation of at least 50 genes in E. coli, is induced when cells experience damage to their DNA and other stresses. Many of the genes induced as part of the SOS response are responsible for DNA repair and cell cycle regulation. Another group of genes induced as part of the SOS response, encoding Y family DNA polymerases, play a role in tolerance to DNA damaging agents at a potentially mutagenic cost.
The Y family DNA polymerases are specialized DNA polymerases that are able to replicate a wide array of damaged DNA substrates, including thymine-thymine dimers, nucleotide base adducts, and abasic sites. The presence of Y family polymerases in cells confers resistance to several classes of DNA damaging agents and environmental toxins. Because they can engage in mutagenic replication of DNA, Y family DNA polymerases are also linked to antibiotic resistance and cancer. A major focus of our research is to understand the specificity of these DNA polymerases for their damaged DNA substrates using protein engineering, molecular modeling and chemical synthesis.
A second focus of the lab is on the dynamics of proteins that regulate DNA damage responses. We are probing the activities of the small protein UmuD that undergoes a self-cleavage reaction and regulates mutagenesis in bacteria through its interactions with Y family DNA polymerases. We also study the dynamics and functions of protein clamps that encircle DNA, providing highly processive and efficient DNA replication by tethering DNA polymerases to their DNA substrates. Using biochemical, biophysical, and genetic approaches, we are investigating the molecular mechanisms by which processivity clamp proteins coordinate the cellular responses to DNA damage and mediate interactions between damage response networks and DNA replication.
6 Hurtig Hall