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.
Carcinogenesis. 2003 Mar;24(3):589-93.
Li Q, Wright SE, Matijasevic Z, Chong W, Ludlum DB, Volkert MR. (2003). The role of human alkyladenine glycosylase in cellular resistance to the chloroethylnitrosoureas. Open Access Publications by UMMS Authors. Retrieved from https://escholarship.umassmed.edu/oapubs/381