EXPRESSION OF T - G-MISMATCH-SPECIFIC THYMIDINE-DNA GLYCOSYLASE AND DNA METHYL TRANSFERASE GENES DURING DEVELOPMENT AND TUMORIGENESIS

In situ hybridization was used to characterize the expression pattern of the T:G mismatch-specific thymidine-DNA glycosylase (TDG) gene, enc oding a DNA repair enzyme which corrects G:T mismatches that result fr om the hydrolytic deamination of 5-methyl cytosines, TDG transcripts w ere uniformly and ubiquitously expressed from 7.5-13.5 days post-coitu m, but were then markedly enriched in specific tissues of the developi ng fetus. At 14.5 gestational days, TDG was strongly expressed in the developing nervous system, thymus, lung, liver, kidney and intestine, At later stages, high levels of expression were detected in the thymus , brain, nasal epithelium and within proliferating regions of the inte stine, skin, kidney, teeth and bone, This pattern of expression strong ly correlated with those of the methyl transferase (MTase) gene, codin g for the enzyme which specifically methylates CpG dinucleotides, and the p53 tumour suppressor gene. However, TDG and MTase were differenti ally expressed during maturation of the male and female germline, We a lso report that tumors occuring in mice which overexpress MMTV-v-Ha-ra s or MMTV-c-myc transgenes or mice heterozygous for p53 gene disruptio n, all show elevated TDG and MTase expression specific to the transfor med tissue.