The role of human alkyladenine glycosylase in cellular resistance to the chloroethylnitrosoureas
Department of Biochemistry and Molecular Pharmacology; Department of Molecular Genetics and Microbiology
Base Sequence; *DNA Glycosylases; DNA Primers; Humans; N-Glycosyl Hydrolases; Nitrosourea Compounds; Substrate Specificity
Cancer Biology | Life Sciences | Medicine and Health Sciences
To investigate the possible role of glycosylase action in causing tumor resistance, a full-length, histidine-tagged human alkyladenine glycosylase has been purified from the cloned human gene contained in a pTrc99A vector propagated in a tag alkA mutant Escherichia coli. This human enzyme releases both 3-methyladenine and 7-methylguanine from methylated DNA but in contrast to previous studies of the bacterial AlkA glycosylase, it does not release any adducts from [(3)H]chloroethylnitrosourea-modified DNA. This finding suggests that the alkyladenine DNA glycosylase-dependent resistance to the toxic effects of the chloroethylnitrosoureas reported previously in the literature may occur by a mechanism other than through direct glycosylase action.
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Citation: Carcinogenesis. 2003 Mar;24(3):589-93.