Alkyladenine DNA glycosylase MagIII (MagIII)

Alkyladenine DNA glycosylase MagIII (MagIII) is a specialized DNA repair enzyme primarily characterized in the extremophilic bacterium Deinococcus radiodurans (UniProt: Q9RVC8). It belongs to the helix-hairpin-helix (HhH-GPD) superfamily of DNA glycosylases and plays a critical role in the base excision repair (BER) pathway by identifying and removing alkylated bases, such as 3-methyladenine and 7-methylguanine, from the DNA backbone (Moe et al., 2000). MagIII functions by flipping the damaged base out of the DNA double helix and into its active site, where it hydrolyzes the N-glycosidic bond to create an apurinic/apyrimidinic (AP) site (Leiros et al., 2005). This activity is essential for the survival of organisms under extreme oxidative and alkylating stress, which would otherwise lead to lethal genomic damage. While MagIII is not currently a target for FDA-approved drugs, it serves as a significant model for understanding DNA damage recognition and repair mechanisms. In drug discovery, bacterial DNA glycosylases are explored as potential targets for sensitizing pathogens to DNA-damaging agents or for developing novel antimicrobial strategies. Its human functional ortholog, N-methylpurine DNA glycosylase (MPG), is a known target in oncology research for sensitizing cancer cells to alkylating chemotherapy.

Other names

3-methyladenine DNA glycosylase IIIMag3DrMagIIIAlkylpurine DNA glycosylase MagIII

Catalyzes the hydrolysis of the N-glycosidic bond of alkylated purine bases, such as 3-methyladenine and 7-methylguanine, to initiate the base excision repair (BER) pathway.