Andrea Lee, Ph.D.

Research Assistant Professor

Training & Education

Dr. Lee received her Ph.D. in Chemistry from University of Wisconsin-Madison under the direction of Professor Judith Burstyn.  She pursued postdoctoral research in single molecule fluorescence microscopy with Dr.Emmanuel Margeat at the Centre Biochimie Structurale in Montpelier France and with Professors Todd Krauss and Kara Bren at the University of Rochester Department of Chemistry before joining the Department of Microbiology and Molecular Genetics as a postdoctoral fellow with Professor Susan Wallace.  She became an assistant professor in MMG in 2018.

Research Interests

Human DNA experiences upwards of 10,000 oxidative damage events per cell per day from both endogenous sources and exogenous agents. In order to prevent these damage events from generating permanent mutations in the genome, all organisms utilize enzymes known as the base excision repair (BER) system to remove and replace sites of oxidative damage in DNA.  A persistent question in the field of DNA repair is how BER enzymes find a site of DNA damage amidst a large excess of highly similar undamaged bases.  We have developed single molecule (SM) microscopy tracking experiments using long extended DNA “tightrope” substrates to watch in real time as individual DNA repair enzymes search for and interact with sites of DNA damage. The BER system is a cascade of enzymes that work in sequence, and we are also interested in elucidating the spatial relationships and interactions between enzymes in the human BER pathway relative to the site of DNA damage.  Another question we would like to answer is how the BER process functions in the context of higher order DNA structure, and we are utilizing SM microscopy to characterize the diffusive behavior of the BER enzymes in the context of chromatin models. 

Single molecule microscopy utilizing long DNA tightropes to investigate glycosylase search mechanisms

 

Featured Publications

Nelson, SR, Kathe, SD, Hilzinger, TS, Averill, AM, Warshaw, DM, Wallace, SS, Lee, AJ (2019) Single molecule glycosylase studies with engineered 8-oxoguanine DNA damage sites show functional defects of a MUTYH polyposis variant. Nucleic Acids Res (in press) DOI: 10.1093/nar/gkz045

Dunn AR, Kad NM, Nelson SR, Warshaw DM, & Wallace SS (2011) Single Qdot-labeled glycosylase molecules use a wedge amino acid to probe for lesions while scanning along DNA. Nucleic Acids Res 39(17):7487-7498.

Nelson SR, Dunn AR, Kathe SD, Warshaw DM, & Wallace SS (2014) Two glycosylase families diffusively scan DNA using a wedge residue to probe for and identify oxidatively damaged bases. Proc Natl Acad Sci U S A 111(20):E2091-2099.

Lee AJ, Warshaw DM, & Wallace SS (2014) Insights into the glycosylase search for damage from single-molecule fluorescence microscopy. DNA Repair (Amst) 20:23-31.

 

MMG Research Assistant Professor

Contact Information

Office: 226 Stafford

Email

Lab Team

Dr. Scott Kathe, Research Analyst

Dr. Shane Nelson, Faculty Scientist (Prof. David Warshaw’s Laboratory)

Morgan McCord, Undergraduate Student