Expression of human and mouse genes encoding polk: testis-specific developmental regulation and AhR-dependent inducible transcription

Backgrounds: Human pol kappa is a newly identified low-fidelity DNA polymer ase. While the enzyme bypasses an abasic site and acetylaminofluorene-adduc t in an error-prone manner, it bypasses benzo[a]pyrene-N2-dG lesions in a m ostly error-free manner by incorporating predominantly dC opposite the bulk y lesions. Benzo[a]pyrene (B[a]P) is activated through intracellular proces s mediated by the arylhydrocarbon receptor (AhR, also called the dioxin rec eptor), which is a ligand-activated transcription factor with high affiniti es for aromatic compounds such as B [a]P and dioxin. Results: We examined promoter structures of the human POLK and mouse Polk g enes to study how their expressions are regulated. The mouse Polk gene is d evelopmentally regulated in testis and utilizes two transcription start sit es during spermato genesis, while it utilizes only one site in tissues othe r than testis. Both of the mouse Polk and the human POLK genes have two AhR -binding sites in the promoter regions and the expression of the mouse Polk gene is indeed enhanced upon AhR-activation. Conclusions: The AhR activation increases expression of the mouse Polk gene and probably the human POLK gene, the product of which bypasses benzo[a]py rene-N2-dG lesions in a mostly accurate manner. Thus, pol kappa seems to fu nction to reduce mutagenesis at benzo[a]pyrene-adducts, although it may als o have a role related to spermato genesis.