Zhigang Wang, Ph.D.
 Professor

Graduate Center for Toxicology

Phone:
(859) 323-5784

Fax:
(859) 323-1059

e-mail:
zwang@uky.edu

website:

http://www.uky.edu/Centers/Toxicology

Dr. Wang's laboratory is interested in two closely related areas: (i) DNA damage-induced mutagenesis; and (ii) DNA excision repair.

Damage-induced mutagenesis. Endogenous and environmental agents frequently attack DNA. DNA damage can cause mutations during replication. Mutagenesis is an important factor during the initiation and progression of human cancers. In the yeast Saccharomyces cerevisiae, it appears that the majority of damage-induced mutations and some spontaneous mutations are generated through the damage-induced mutagenesis pathway. A similar mutagenesis pathway is most likely operational in humans. Hence, understanding damage-induced mutagenesis is a key to the understanding of carcinogenesis. Furthermore, this mutagenesis pathway offers an exciting novel target for cancer prevention and suppression through therapeutic inhibition of the pathway. Our objectives in this area are (a) to understand the molecular mechanism of the damage-induced mutagenesis pathway; and (b) to explore this mutagenesis pathway as a target for cancer prevention and suppression.

DNA excision repair. DNA excision repair is a major cellular response to DNA damage. It consists of base excision repair (BER) and nucleotide excision repair (NER). Defects in NER can lead to a predisposition to cancers as manifested in the human hereditary disease xeroderma pigmentosum (XP). We face two challenges in the area of excision repair: (a) repair of nucleosomal DNA; and (b) transcription-coupled repair. Our studies of excision repair rely on the eukaryotic model organism, the yeast S. cerevisiae. We are using molecular, biochemical, and genetic techniques to study the mechanism of DNA excision repair in this model system.

Research Publications/Presentations

Xie, Z., Braithwaite, E., Guo, D., Zhao, B., Geacintov, N. E, and Wang, Z.  2003. Mutagenesis of benzo[a]pyrene diol epoxide in yeast: requirement for DNA polymerase z and involvement of DNA polymerase h. Biochemistry 42:11253-11262. 

Guo, D., Xie, Z., Shen, H., Zhao, B., and    Wang, Z. 2004. Translesion synthesis of acetylaminofluorene-dG adducts by DNA polymerase z is stimulated by yeast Rev1 protein. Nucleic Acids Res. 32: 1122-1130. 

Zhao, B., Xie, Z., Shen, H., and Wang, Z.  2004. Role of DNA polymerase h in the bypass of abasic sites in yeast cells. Nucleic Acids Res. 32: 3984-3994. 

Wu, X., Braithwaite, E., and Wang, Z. 1999. DNA ligation during excision repair in yeast cell-free extracts is specifically catalyzed by the CDC9 gene product. Biochemistry 38: 2628-2635.

Lin, W., Xin, H., Wu, X., Zhang, Y., and Wang, Z. 1999. The human REV1 gene codes for a DNA template-dependent dCMP transferase. Nucleic Acids Res.  27: 4468-4475.

Yuan, F., Zhang, Y., Rajpal, D., Wu, X., Duo, D., Wang, M., Taylor, J.-S., and Wang, Z. 2000. Specificity of DNA lesion bypass by the yeast DNA polymerase h. J. Biol. Chem. 275: 8233-8239.

Xin, H., Lin, W., Sumanasekera, W., Zhang, Y., Wu, X., and Wang, Z. 2000.  The human RAD18 gene product interacts with HHR6A and HHR6B. Nucleic Acids Res. 28: 2847-2854.  

Zhang, Y., Yuan, F., Wu, X., and Wang, Z. 2000. Preferential incorporation of G opposite template T by the low fidelity human DNA polymerase i. Mol. Cell. Biol. 20: 7099-7108.  

Zhang, Y., Yuan, F., Wu, X., Wang, M., Rechkoblit, O., Taylor, J.-S., Geacintov, N. E., and Wang, Z. 2000. Error-free and error-prone lesion bypass by human DNA polymerase k in vitro.  Nucleic Acids Res. 28: 4138-4146.  

Zhang, Y., Yuan, F., Xin, H., Wu, X., Rajpal, D. K., Yang, D., and Wang, Z. 2000. Human DNA polymerase k synthesizes DNA with extraordinarily low fidelity.  Nucleic Acids Res. 28: 4147-4156.  

Zhang, Y., Yuan, F., Wu, X., Rechkoblit, O., Taylor, J.-S., Geacintov, N. E., and Wang, Z. 2000. Error-prone lesion bypass by human DNA polymerase h. Nucleic Acids Res. 28: 4717-4724.     

Wu, X., Guo, D., Yuan, F., and Wang, Z. 2001. Accessibility of DNA polymerases to repair synthesis during nucleotide excision repair in yeast cell-free extracts. Nucleic Acids Res. 29: 3123-3130.  

Guo, D., Wu, X., Rajpal, D. K., Taylor, J.-S., and Wang, Z. 2001. Translesion synthesis by yeast DNA polymerase z from templates containing lesions of ultraviolet radiation and acetylaminofluorene. Nucleic Acids Res. 29: 2875-2883.  

Zhang, Y., Wu, X., Yuan, F., Xie, Z., and Wang Z. 2001. Highly frequent frameshift DNA synthesis by human DNA polymerase m. Mol. Cell. Biol. 21: 7995-8006.    

Zhang, Y., Wu, X., Rechkoblit, O., Geacintov, N. E., Taylor, J.-S., and Wang, Z. 2002. Response of human REV1 to different DNA damage: preferential dCMP insertion opposite the lesion. Nucleic Acids Res. 30: 1630-1638.  

Zhang, Y., Wu, X., Guo, D., Rechkoblit, O., Taylor, J.-S., Geacintov, N. E., and Wang, Z. 2002. Lesion bypass activities of human DNA polymerase m. J. Biol. Chem. 277: 44582-44587.  

Xie, Z., Braithwaite, E., Guo, D., Zhao, B., Geacintov, N. E, and Wang, Z.  2003. Mutagenesis of benzo[a]pyrene diol epoxide in yeast: requirement for DNA polymerase z and involvement of DNA polymerase h. Biochemistry. (in press).