MGMT : its role in cancer aetiology and cancer therapeutics

The DNA-repair protein O6 -alkylguanine DNA alkyltransferase (AGT) has a wide range of activity in normal tissues and its evolutionary conservation indicates a fundamental role in cell physiology and maintenance of the genome. Through removal of alkylating lesions at O6 of guanine, AGT protects agai...

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Bibliographic Details
Published inNature reviews. Cancer Vol. 4; no. 4; pp. 296 - 307
Main Author Gerson, Stanton L
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 01.04.2004
Subjects
Animals
Cancer
Cell Transformation, Neoplastic - genetics
Control
DNA damage
DNA Methylation
DNA Repair - physiology
Drug Resistance, Neoplasm - genetics
Genetic aspects
Genetic Therapy
Humans
Methyltransferases
Neoplasms - drug therapy
Neoplasms - enzymology
Neoplasms - etiology
O-Methylguanine-DNA Methyltransferase - genetics
O-Methylguanine-DNA Methyltransferase - physiology
Physiological aspects
Promoter Regions, Genetic
Risk factors
United States
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Summary:The DNA-repair protein O6 -alkylguanine DNA alkyltransferase (AGT) has a wide range of activity in normal tissues and its evolutionary conservation indicates a fundamental role in cell physiology and maintenance of the genome. Through removal of alkylating lesions at O6 of guanine, AGT protects against mutagenesis and malignant transformation. In tumours, AGT provides resistance to treatment with alkylating agents, unless expression is lost by methylation of the promoter of the gene encoding AGT -- O6 -methylguanine-DNA-methyltransferase (MGMT) -- or there is direct inhibition of AGT activity. When overexpressed in stem cells, MGMT serves as a drug-selection gene for gene therapy and protects normal tissues from the toxic effects of chemotherapy.
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ISSN:1474-175X
1474-1768
DOI:10.1038/nrc1319