Partial purification and characterization of human 5-methylcytosine-DNA glycosylase

The molecular mechanisms by which DNA 5-methylcytosine content is modulated are incompletely understood, Reduction of DNA 5-methylcytosine content has been correlated with the transition from hyperplasia to adenoma in the genesis of human adenocarcinoma of the colon, 5-methylcytosine-DNA glycosylase removes 5-methylcytosine from DNA as a free base, but its involvement in this process is unknown, The 5-methylcytosine-DNA glycosylase activity in HeLa nuclear extracts has been partially purified, with a 460-fold enrichment, and characterized, This activity is specific for 5-methylcytosine at CpG sites in fully methylated DNA; hemimethylated DNA is not a significant substrate, DIVA containing unmethylated cytosines is not cleaved by the enzyme, There is an absolute requirement for Mg2+ ions for the activity, which is inhibited by EDTA, This 5-methylcytosine-DNA glycosylase activity could be involved in carcinogenesis, transcription, replication, differentiation and development through resultant DNA hypomethylation following enzymatic removal of 5-methylcytosine from DNA.