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Esteller, Manel; Garcia-Foncillas, Jesus; Andion, Esther; Goodman, Steven N; Hidalgo, Oscar F; Vanaclocha, Vicente; Baylin, Stephen B; Herman, James G
The New England journal of medicine, 11/2000, Letnik: 343, Številka: 19Journal Article
Alkylating agents are highly reactive molecules that cause cell death by binding to DNA. 1 , 2 The most frequent site of alkylation in DNA is the O 6 position of guanine. Alkylation here forms cross-links between adjacent strands of DNA, 1 which explains how the nitrosoureas, tetrazines, and procarbazine kill cells. The cross-linking of double-stranded DNA by alkylating agents is inhibited by the cellular DNA-repair protein O 6 -methylguanine-DNA methyltransferase (MGMT), also known as O 6 -alkylguanine-DNA alkyltransferase. The MGMT protein rapidly reverses alkylation at the O 6 position of guanine, 3 , 4 thereby averting the formation of lethal cross-links. Through this mechanism, MGMT causes resistance to . . .
