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Review
. 2007 Aug 1;6(8):1064-70.
doi: 10.1016/j.dnarep.2007.03.007. Epub 2007 May 7.

MGMT: a personal perspective

Sankar Mitra  1
Affiliations
Review

MGMT: a personal perspective

Sankar Mitra. DNA Repair (Amst). .

Abstract

This review describes the history of studies on alkylation damage of mammalian genomes and its carcinogenic consequences that led to the discovery of a unique DNA repair protein, named MGMT. MGMT repairs O(6)-alkylguanine, a critical mutagenic lesion induced by alkylating agents. The follow-up studies in mammalian cells following the discovery of the ubiquitous repair protein in E. coli are summarized.

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Figures

Fig. 1
Fig. 1. MGMT Assay
Two complementary quantitative assays for MGMT were developed using [3H]-labeled m6G-containing DNA substrates. (Only the O6-methyldeoxyguanosine moiety is shown here for convenience.) In (I), a synthetic oligodeoxynucleotide containing m6G labeled with [3H] at C-8 is used as the substrate. Demethylation of m6G by MGMT generates [3H]G which is then separated from [3H]m6G by HPLC. The amount of MGMT equals that of [3H]G. In (II), DNA methylated with a [3H]methylating agent is used as the substrate. MGMT is radiolabeled at the methyl-acceptor Cys during the methyltransferase reaction. After hydrolysis, [3H]methylCys is quantitated.
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