MGMT: a personal perspective - PubMed (original) (raw)

Review

MGMT: a personal perspective

Sankar Mitra. DNA Repair (Amst). 2007.

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. 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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MGMT: a personal perspective - PubMed (original) (raw)