Figure 4: Diagram showing how alkylating drugs temozolomide (TMZ), nimustine (ACNU), and carmustine (BCNU) act damaging DNA by introducing alkyl residues in the O 6 position of guanine, thus producing DNA interstrand cross-links. The DNA repair O 6 -methylguanine DNA methyltransferase (MGMT) reverses the formation of adducts at the O 6 position of guanine. MGMT transfers the alkyl group from the O 6 -guanine to an active cysteine within its own sequence in a reaction that inactivates one MGMT molecule for each lesion repaired. The alkylated MGMT protein then becomes detached from DNA and is targeted for degradation by ubiquitination.