The role of human alkyladenine glycosylase in cellular resistance to the chloroethylnitrosoureas.
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.
Li
Qiong
Q
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Wright
Stephen E
SE
Matijasevic
Zdenka
Z
Chong
Wincha
W
Ludlum
David B
DB
Volkert
Michael R
MR
D001483:Base Sequence; D045647:DNA Glycosylases; D017931:DNA Primers; D006801:Humans; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D013379:Substrate Specificity
D017931:DNA Primers; D009607:Nitrosourea Compounds; C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases