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Dr. Wang's laboratory is interested in two closely related areas: DNA damage-induced mutagenesis and 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 Polz mutagenesis pathway. Apparently similar mutagenesis pathway is also 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. Recent studies suggest that the Y-family DNA polymerases participate in DNA lesion bypass, some of which are mutagenic. Our objectives in this area are (a) to understand molecular mechanisms of damage-induced mutagenesis; and (b) to explore the Polz 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). 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.