At a concentration of 5 x 10(-9) M of hemi-methylated DNA (one order of magnitude below the K(m)), MCF-7 (a human breast carcinoma cell line) nuclear extracts potentiate the activity of 5-methylcytosine DNA glycosylase (5-MCDG, alias G/T mismatch DNA glycosylase). Depending on the ratio between MCF-7 nuclear extracts and 5-MCDG, there is an up to 10-fold increase in 5-MCDG activity. The potentiation of 5-MCDG by MCF-7 nuclear extracts requires an estradiol response element adjacent to the hemi-methylated site. Depletion of the estradiol receptor from MCF-7 nuclear extracts with specific antibodies abolishes the potentiation of 5-MCDG activity. The estradiol receptor present in MCF-7 nuclear extracts can be precipitated with antibodies directed against 5-MCDG. Reciprocally, antibodies directed against the estradiol receptor precipitate 5-MCDG. The results indicate the formation of a complex between the estradiol receptor and 5-MCDG.