Alkyladenine DNA glycosylase (AAG)

Alkyladenine DNA glycosylase (AAG), also known as N-methylpurine DNA glycosylase (MPG), is a key enzyme in the base excision repair (BER) pathway that identifies and removes damaged purine bases from the genome [UniProt: P13010]. It possesses a broad substrate specificity, recognizing lesions such as 3-methyladenine, 7-methylguanine, and hypoxanthine, which are generated by both endogenous processes and exogenous alkylating agents [PubMed: 23143586]. By catalyzing the hydrolysis of the N-glycosidic bond, AAG creates an apurinic/apyrimidinic (AP) site, initiating a cascade that restores DNA integrity. In clinical oncology, AAG expression levels are often linked to the resistance of tumors to alkylating chemotherapies, such as temozolomide, as the enzyme efficiently repairs the cytotoxic damage intended by the treatment [PubMed: 21177855]. Consequently, AAG is being investigated as a therapeutic target where its inhibition could sensitize cancer cells to chemotherapy or modulate inflammatory responses [NCBI Gene: 4350]. However, the balance of AAG activity is delicate, as excessive repair or the accumulation of unrepaired AP sites can lead to strand breaks and genomic instability, contributing to various disease states including neurodegeneration and ischemia-induced tissue damage [PubMed: 19233843].

Other names

N-methylpurine DNA glycosylaseMPGANPGADPG3-methyladenine DNA glycosylaseDNA-3-methyladenine glycosylase

Inhibition of the enzyme's glycosylase activity to prevent the excision of alkylated bases, thereby sensitizing cells to alkylating agents [PubMed: 21177855].