The low-fidelity polymerase eta (
poleta) is required for bypass of UV-induced
pyrimidine dimers inserting
adenine nucleotides opposite these lesions. Mutations in the
poleta gene are responsible for the genetic defect in
xeroderma pigmentosum variant patients. To study if the lack of
poleta significantly elevates spontaneous mutation frequency in various organs and tissues of the mouse, we crossed
poleta-deficient mice with transgenic mice harboring a chromosomally integrated lacZ-plasmid reporter construct. In cultured embryonic fibroblasts from the lacZ-
poleta(-/-) mice, 2.5 J/m(2) UV irradiation induced approximately 5-fold more mutations than in cells from lacZ control mice, in which an approximately 3-fold increase in mutation frequency was found compared with the normal level. Whereas untreated cells harbored mainly 1-bp deletions, UV induced both transitions and transversions, with the latter type more highly represented in the
poleta-null cells than in the controls. No difference in mutation induction between the
poleta-null cells and the wild-type cells was observed
after treatment with
N-ethyl-N-nitrosourea. Having shown the validity of the lacZ model to accurately identify
poleta-associated mutagenesis, we then determined the mutant frequency at the lacZ locus in liver, spleen, and small intestine of 12-month-old animals. No differences were found between
poleta-null, heterozygous, or littermate control mice. We conclude that the
poleta defect is specific for UV damage and has no effect on in vivo mutagenesis in mice.