Expression of human and mouse genes encoding polkappa: testis-specific developmental regulation and AhR-dependent inducible transcription.
BACKGROUND
Human polkappa is a newly identified low-fidelity DNA polymerase. While the enzyme bypasses an abasic site and acetylaminofluorene-adduct in an error-prone manner, it bypasses benzo[a]pyrene-N2-dG lesions in a mostly error-free manner by incorporating predominantly dC opposite the bulky lesions. Benzo[a]pyrene (B[a]P) is activated through intracellular process mediated by the arylhydrocarbon receptor (AhR, also called the dioxin receptor), which is a ligand-activated transcription factor with high affinities for aromatic compounds such as B[a]P and dioxin.


RESULTS
We examined promoter structures of the human POLK and mouse Polk genes to study how their expressions are regulated. The mouse Polk gene is developmentally regulated in testis and utilizes two transcription start sites during spermatogenesis, while it utilizes only one site in tissues other 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]pyrene-N2-dG lesions in a mostly accurate manner. Thus, polkappa seems to function to reduce mutagenesis at benzo[a]pyrene-adducts, although it may also have a role related to spermatogenesis.
Ogi
T
T
Institute for Virus Research, Kyoto University, Shogoin-Kawaramachi 53, Sakyo-ku, Kyoto 606-8507, Japan.
Mimura
J
J
Hikida
M
M
Fujimoto
H
H
Fujii-Kuriyama
Y
Y
Ohmori
H
H
D000818:Animals; D001483:Base Sequence; D001564:Benzo(a)pyrene / Q000494:pharmacology; D001665:Binding Sites; D018076:DNA, Complementary; D004259:DNA-Directed DNA Polymerase; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism / Q000502:physiology*; D012689:Sequence Homology, Nucleic Acid; D013737:Testis / Q000201:enzymology*; D014158:Transcription, Genetic / Q000502:physiology*; D000099270:Y-Family DNA Polymerases
D001564:Benzo(a)pyrene; D018076:DNA, Complementary; D004259:DNA-Directed DNA Polymerase; D008748:Methylcholanthrene; D011506:Proteins; D018336:Receptors, Aryl Hydrocarbon; C404302:POLK protein, human; D000099270:Y-Family DNA Polymerases; C498613:Polk protein, mouse