Date on Master's Thesis/Doctoral Dissertation

8-2008

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Committee Chair

McGregor, W. Glenn

Subject

Cancer--Genetic aspects

Abstract

The Y family of DNA polymerases in higher eukaryotes contains at least four members which are implicated in potentially error-prone replication through unrepaired damage in the genome. These proteins are encoded by the REV1, POLH, POLI, and POLK genes. An inherited deficiency in one of these DNA polymerases (POL?) is the molecular defect in the cancer prone xeroderma pigmentosum (XP) variant syndrome, making POL? the most studied member of this family. However, there exist critical gaps in our knowledge on the function of the other known Y family members (POL I, POL K, and REV1). The goal of this proposal is to investigate the in vivo function of DNA POLI, and the hypothesis that DNA polymerase I acts as a mutagenic polymerase in translesion synthesis and as a tumor suppressor through a separate mechanism. To test this hypothesis, the mutagenic effects of chemical carcinogens which form structually different adducts will be examined in cells lacking POL? and/or POL I . To characterize the tumor suppressor function(s) of POL I, cell cycle progression will be monitored after UV in POL I null cells along with global gene expression. Finally, a novel mouse model will be used to determine the effect of pol? and/or polI deficiency on UV- and chemically-induced skin cancer.

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