Dr. Joann Sweasy

Dr. Joann  Sweasy


Maintenance of Genome Stability

Oxidative DNA damage occurs at a rate of about 20,000 lesions per cell per day. The base excision repair (BER) system repairs this DNA damage and therefore maintains genome stability. BER may be a tumor suppressor mechanism. The research in my lab is focused on the functional characterization of mutants encoding variant BER enzymes and their roles in cancer and other diseases. We study germline Single Nucleotide Polymorphisms (SNPs) and mutants that arise in tumors. Our research has shown that both tumor-associated variants and germline variants of BER induce cellular transformation in immortal cells in culture. The molecular mechanism of transformation results from genomic instability.

Our laboratory also focuses on the function of variants of other DNA repair processes including homology directed repair. Deficiencies in this process also lead to genomic instability and we are working on characterizing the contribution of specific variants to this process.

Meiosis relies on several DNA repair enzymes and we have focused our efforts on the roles of DNA polymerase beta (Pol beta) in this process. We have shown that proper function of Pol beta is critical for Prophase I of meiosis and are now studying the roles of Pol beta and its interacting proteins in meiosis, using a combined genetic and biochemical approach.

The biochemical functions of DNA repair variants identified in the germline and in tumors are important for understanding their aberrant functions in cells. Our laboratory uses a combination of enzymology and fluorescence based assays to study these DNA repair variants in order to elucidate their roles in cancer and other diseases.

208A Stafford

208 Stafford


Dr. Sweasy received her Ph.D. at Rutgers University under the direction of Evelyn M. Witkin. She did postdoctoral research with Lawrence A. Loeb at the University of Washington where she initiated her research into mechanisms of genomic instability induced by mutant DNA polymerases.


Galick, H.A., Kathe, S., Liu, M., Robey-Bond, S., Kidane, D., Wallace, S.S., Sweasy, J.B. (2013) Germ-line variant of Human NTH1 DNA glycosylase induces genomic instability and cellular transformation. Proc. Natl., Acad. Sci. 110: 14314-9

Senejani, A.G, Liu, Y., Kidane, D., Maher, S.E., Zeiss, C.J., Park, H.J., Kashgarian, M., McNiff, J.M., Zelterman, D., Bothwell, A.L.M., Sweasy, J.B. (2014) Mutation of POLB causes lupus in mice. Cell Reports 6:1-8

Towle-Weicksel, J., Dalal, S., Sohl, C.D, Doublie, S., Anderson, K.A., Sweasy, J.B. (2014) Fluorescence resonance energy transfer studies of DNA polymerase β: the critical role of fingers domain movements and a novel non-covalent step during nucleotide selection. J. Biol. Chem. 289: 16541-16550

Sjolund, A., Nemec, A.A., Paquet, N., Prakash, A., Sung, P, Doublie, S., Sweasy, J.B. (2014) A Germline Polymorphism of Thymine DNA Glycosylase Induces Genomic Instability and Cellular Transformation. PLoS Genet. 10:e1004753

Kidane, D., Murphy, D., Sweasy. J.B. (2014) Accumulation of Abasic Sites Induces Genomic Instability in Normal Human Gastric Epithelial Cells During Helicobacter pylori Infection. Oncogenesis. 3:e128

All Sweasy publications