Journal Article

The role of human alkyladenine glycosylase in cellular resistance to the chloroethylnitrosoureas

Qiong Li, Stephen E. Wright, Zdenka Matijasevic, Wincha Chong, David B. Ludlum and Michael R. Volkert

in Carcinogenesis

Volume 24, issue 3, pages 589-593
Published in print March 2003 | ISSN: 0143-3334
Published online March 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/24.3.589
The role of human alkyladenine glycosylase in cellular resistance to the chloroethylnitrosoureas

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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 [3H]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.

Keywords: AAG, alkyladenine DNA glycosylase; AGT, O6-alkylguanine-DNA alkyltransferase; CNU, N-(2-chloroethyl)-N-nitrosourea; hAAG, human alkyladenine DNA glycosylase; IPTG, isopropyl β-d-thiogalactopyranoside; m3A, 3-methyladenine; m7G, 7-methylguanine; MMS, methyl methanesulfonate; MNU, N-methyl-N-nitrosourea.

Journal Article.  4598 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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