Genetics and Biochemistry

Dr. Weiguo Cao

Weiguo Cao


Ph.D. Microbiology
1992, University of Idaho

Contact Information
Office: 049 Life Sciences Building
Phone: (864) 656-4176
Website: Cao Lab Website

Research Focus Areas
DNA Damage and Repair
Nitrosative Stress


Research Activities

Our research focuses on understanding the molecular and cellular mechanisms of DNA repair. DNA damage is caused by UV and ionizing radiation, oxidation, alkylation, deamination, and hydrolysis. As a result, DNA bases may be modified and DNA strands may be broken or crosslinked. These changes in DNA structures may hinder normal DNA transactions such as replication or generate mutations due to abnormal base pairing. To prevent genotoxic effects of DNA damage, all living cells are equipped with multitude of DNA repair systems to remove DNA lesions and to maintain genome integrity. Compromise in DNA repair capacity increases mutation and chromosomal abnormality and ultimately leads to disease such as cancer, aging and neurodegeneration.

Deamination is a hydrolytic or oxidative process caused by spontaneous hydrolysis or exposure to nitric oxide, nitrous acid, or N-nitrosoindoles. DNA may be exposed to these nitrosative compounds generated during endogenous cellular metabolism or through environmental sources. Deamination modifies adenine to hypoxanthine (or inosine in DNA), cytosine to uracil, and guanine to xanthine or oxanine. These lesions may cause mutations if left unrepaired (see the diagram below).

DNA Damage and Repair

Diagram 1. Base deamination and mutagenicity. Exposure of DNA to nitrosative stress causes base deamination: C to U, A to I, G to X or O. Deaminated bases may cause mispair during DNA replication. For example, uracil, as the deaminated product of cytosine, pairs with A instead of G, resulting in G to A transition. Consequently, a C/G base pair is mutated to an T/A base pair.

Deaminated DNA bases are repaired by two major pathways. Base Excision Repair (BER) is initiated by a DNA glycosylase that removes a damage base from the DNA. Alternative Excision Repair (AER) is initiated by endonuclease V that recognizes deaminated DNA lesions and initiates DNA repair by making a 3' incision to the lesion. Using biochemical, enzyme kinetics, structural biology, genetic and systems biology approaches, we are addressing questions related to the molecular recognition mechanisms, protein-DNA interactions, structure and function relationship, functional redundancy and coordination of repair proteins, and DNA repair networks. We are interested in understanding the role of DNA repair in bacterial pathogenicity and host inflammatory response, in cancer development and other diseases. The major current research areas and interests encompass (1) Biochemistry of endonuclease V-mediated repair in bacterial and mammalian systems; (2) Biochemistry of DNA glycosylases in archaea, bacteria and humans; (3) Evolution of DNA repair glycosylases and role of DNA repair in evolution; (4) Screening and identification of novel repair genes and stress-resistance genes and repair activities; (5) Nitrosative stress and protein modification.

Grant Support

National Institutes of Health
Xanthine DNA Glycosylase in Mammalian Systems

U.S. Department of Defense
New Protein Modification under Nitrosative Stress



Ralph E. Powe Junior Faculty Enhancement Award, Oak Ridge Associated Universities

Charles H. Revson Foundation Fellow in Biomedical Research


Graduate Students


Courses Taught

BCHM 4310/6310
Physical Approach to Biochemistry

BCHM 4330/6330
General Biochemistry

BCHM 8220

BCHM 8140
Advanced Biochemistry

GEN/BCH 8900
Special Topics in Biochemistry and Genetics




Recent Publications

Lee, H. W., Dominy, B. N., and Cao, W. (2011) A New Family of Deamination Repair Enzymes in the Uracil DNA Glycosylase Superfamily, J Biol Chem, 286: 31282. 
(Highlighted in Spotlight, Chemical Research in Toxicology, 24: 1161).

Mi, R., Abole, A. K., and Cao, W. (2011) Dissecting endonuclease and exonuclease activities in endonuclease V from Thermotoga maritima, Nucleic Acids Res, 39: 536-544.

Lee, H.-W., Brice, A. R., Wright, C. B., Dominy, B. N. and Cao, W. (2010). Identification of Escherichia coli MUG as a Robust Xanthine DNA Glycosylase, J Biol Chem, 285: 41483-41490.

Park, S.-H., Lee, H.-W. and Cao, W. (2010). Screening of Nitrosative Stress Resistance Genes in Coxiella burnetii: Involvement of Nucleotide Excision Repair. Microbial Pathogenesis, 49: 323-320.

Lee, H.-W., Hitchcock, T. M., Park, S.-H., Mi, R., Kraft, J. D., Luo, J. and Cao, W. (2010). Involvement of Thioredoxin Domain-containing 5 in Resistance to Nitrosative Stress. Free Radical Biology & Medicine, 49: 872-880.

Mi, R., Dong, L., Kaulgud, T., Hackett, K. W., Dominy, B. N., and Cao, W. (2009) Insights from xanthine and uracil DNA glycosylase activities of bacterial and human SMUG1: switching SMUG1 to UDG, J Mol Biol 385: 761-778.

Dalhus, B., Arvai, A. S., Rosnes, I., Olsen, O. E., Backe, P. H., Alseth, I., Gao, H., Cao, W., Tainer, J. A., and Bjoras, M. (2009) Structures of endonuclease V with DNA reveal initiation of deaminated adenine repair, Nature Struct Mol Biol, 16: 138-143.
(Highlighted in News & Views, Nature Struct Mol Biol, 16: 102-104).

Dong, L., Mi, R., Glass, R. A., Barry, J. N., and Cao, W. (2008) Repair of deaminated base damage by Schizosaccharomyces pombe thymine DNA glycosylase, DNA Repair, 7: 1962-1972.

Dong, L., Meira, L. B., Hazra, T. K., Samson. L. D. and Cao, W. (2008) Oxanine DNA Glycosylase Activities in Mammalian Systems, DNA Repair, 7: 128-134.

Lin, J., Gao, H., Schallhorn, K. A., Harris, R. M., Cao, W., and Ke, P.-C. (2007) Lesion Recognition and Cleavage by Endonuclease V: A Single-Molecule Study, Biochemistry, 46: 7132-7137.