Beyond Genetics in Glioma Pathways: The Ever-Increasing Crosstalk between Epigenomic and Genomic Events
Figure 4
Diagram showing how alkylating drugs temozolomide (TMZ), nimustine (ACNU), and carmustine (BCNU) act damaging DNA by introducing alkyl residues in the position of guanine, thus producing DNA interstrand cross-links. The DNA repair -methylguanine DNA methyltransferase (MGMT) reverses the formation of adducts at the position of guanine. MGMT transfers the alkyl group from the -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.
